Compositions and methods for delivering targeted therapeutics to bone

Abstract

SOLUTION: Provided herein are polypeptides comprising a therapeutic target to be delivered to an organ or tissue, and uses thereof.SELECTED DRAWING: Figure 16B

Description

[Technical Field]

[0001] Priority claims This application claims the benefit of U.S. Provisional Patent Application No. 63 / 010,639, filed April 15, 2020, which is incorporated herein by reference in its entirety.

[0002] Government Rights This invention was made with government support under W81XWH-18-C-0182 and W81XWH-15-C-0028 awarded by the Department of Defense. The government has certain rights in this invention.

[0003] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in ASCII format and is incorporated herein by reference. The ASCII copy created on April 13, 2021, is named 50222-705_601_SL.txt and is 650,053 bytes in size. [Background technology]

[0004] An average of 6 million people suffer bone fractures annually in the United States. Of these bone defects, the majority heal without problems. However, 5–10% heal poorly or not at all (American Academy of Orthopaedic Surgeons). Large bone defects, also known as critical-size bone defects, may not heal spontaneously and may result in nonunion. Nonunion occurs when there are no signs of healing for at least three months and no further healing is expected (American Academy of Orthopaedic Surgeons). Currently, bone grafting is considered the "gold standard" for treating large or segmental bone defects. However, this treatment has limitations, including donor site pain, risk of rejection, limited donor supply, and risk of infection transmission.

[0005] Repair of severe and complex bone and cartilage defects is further limited by insufficient tissue regeneration in implanted orthopedic scaffolds. Reasons for insufficient tissue regeneration include the loss of implanted progenitor cells within 48 hours of implantation and a lack of progenitor cells. Another factor is the inability of current orthopedic scaffolds to promote sufficient tissue regeneration. Summary of the Invention

[0006] The present disclosure is based on the discovery that the use of a composition comprising a mammalian growth factor (e.g., bone morphogenetic protein 2 (BMP-2)) or a functional portion thereof and a targeting polypeptide (e.g., a polypeptide that binds to bone or a carrier material) can significantly improve bone healing and accelerate tissue regeneration. In non-limiting embodiments, the targeting polypeptide is bound to a carrier material such as calcium phosphate (e.g., β-tricalcium phosphate, i.e., β-TCP), hydroxyapatite, or other materials suitable for use in implantable devices. Accordingly, provided herein are chimeric polypeptides comprising one or more targeting polypeptides and a mammalian growth factor, compositions comprising any of these chimeric polypeptides (and, optionally, a carrier material), and methods for promoting bone or cartilage formation, replacing and / or repairing bone or cartilage, and treating fractures or bone loss, including the administration of any of these compositions. The compositions and methods provided herein can increase and maintain the number of progenitor cells at sites of bone and / or cartilage damage via stem cell entrapment. The compositions and methods provided herein can also be applied to soft tissue repair or localized delivery of therapeutic agents.

[0007] Provided herein are polypeptide compositions comprising a targeting polypeptide comprising a sequence at least 80% identical to SEQ ID NO:22 (LLADTTHHRPWT VIGESTHHRPWS IIGESSHHKPFT GLGDTTHHRPWG ILAESTHHKPWT) and a therapeutic polypeptide comprising a sequence at least 80% identical to a sequence selected from SEQ ID NOs:32, 46-71, 73-77, 79-101, 152, 168, 176, 268. In some embodiments, the therapeutic polypeptide comprises a sequence at least 90% identical to a sequence selected from SEQ ID NOs:32, 46-71, 73-77, 79-101, 152, 168, 176, 268. In some embodiments, the therapeutic polypeptide comprises a sequence selected from SEQ ID NOs:32, 46-71, 73-77, 79-101, 152, 168, 176, 268. In some embodiments, the therapeutic polypeptide comprises a sequence at least about 80%, 85%, 90%, or 95% identical to SEQ ID NO: 32. In some embodiments, the therapeutic polypeptide comprises SEQ ID NO: 32. In some embodiments, the targeting polypeptide comprises a sequence at least 90% or 95% identical to SEQ ID NO: 22. In some embodiments, the targeting polypeptide comprises ...

[0008] Also provided herein is a polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:551 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), wherein the polypeptide composition comprises X, wherein X comprises SEQ ID NO:22 (LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWT). In some embodiments, the composition comprises a sequence at least about 90% or 95% identical to SEQ ID NO:551.

[0009] Also provided herein is a polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO: 639 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), wherein the polypeptide composition comprises X, wherein X comprises SEQ ID NO: 2 (VIGESTHHRPWS). In some embodiments, the composition comprises a sequence at least about 90% or 95% identical to SEQ ID NO: 639.

[0010] Also provided herein is a polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:519 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), wherein the polypeptide composition comprises X, wherein X comprises SEQ ID NO:6 (IIGESSHHKPFT). In some embodiments, the composition comprises a sequence at least about 90% or 95% identical to SEQ ID NO:519.

[0011] Also provided herein is a polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:521 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), wherein the polypeptide composition comprises X, wherein X comprises SEQ ID NO:7 (GLGDTTHHRPWG). In some embodiments, the composition comprises a sequence at least about 90% or 95% identical to SEQ ID NO:521.

[0012] Also provided herein is a polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:515 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), wherein the polypeptide composition comprises X, wherein X comprises SEQ ID NO:4 (ILAESTHHKPWT). In some embodiments, the composition comprises a sequence at least about 90% or 95% identical to SEQ ID NO:515.

[0013] Also provided herein are polypeptide compositions comprising a sequence at least about 80% identical to SEQ ID NO: 501. In some embodiments, the sequence is at least about 90% or 95% identical to SEQ ID NO: 501. In some embodiments, the sequence comprises SEQ ID NO: 501.

[0014] Also provided herein are polypeptide compositions comprising a sequence at least about 80% identical to SEQ ID NO: 507. In some embodiments, the sequence is at least about 90% or 95% identical to SEQ ID NO: 507. In some embodiments, the sequence comprises SEQ ID NO: 507.

[0015] Also provided herein are polypeptide compositions comprising a sequence at least about 80% identical to SEQ ID NO: 506. In some embodiments, the sequence is at least about 90% or 95% identical to SEQ ID NO: 506. In some embodiments, the sequence comprises SEQ ID NO: 506.

[0016] Also provided herein are polypeptide compositions comprising a sequence at least about 80% identical to SEQ ID NO: 505. In some embodiments, the sequence is at least about 90% or 95% identical to SEQ ID NO: 505. In some embodiments, the sequence comprises SEQ ID NO: 505.

[0017] Also provided herein are polypeptide compositions comprising a sequence at least about 80% identical to SEQ ID NO: 504. In some embodiments, the sequence is at least about 90% or 95% identical to SEQ ID NO: 504. In some embodiments, the sequence comprises SEQ ID NO: 504.

[0018] Also provided herein are polypeptide compositions comprising a sequence at least about 80% identical to SEQ ID NO: 503. In some embodiments, the sequence is at least about 90% or 95% identical to SEQ ID NO: 503. In some embodiments, the sequence comprises SEQ ID NO: 503.

[0019] Also provided herein are polypeptide compositions comprising a sequence at least about 80% identical to SEQ ID NO: 502. In some embodiments, the sequence is at least about 90% or 95% identical to SEQ ID NO: 502. In some embodiments, the sequence comprises SEQ ID NO: 502.

[0020] Also provided herein are polypeptide compositions comprising a targeting polypeptide comprising a sequence at least 80% identical to SEQ ID NO: 22 (LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWT) and a therapeutic polypeptide comprising a bone morphogenetic protein (BMP). In some embodiments, the BMP is BMP-2.

[0021] Also provided herein are nucleic acids encoding the polypeptide compositions described herein. Also provided are vectors containing the nucleic acids.

[0022] Also provided herein are devices comprising the polypeptide compositions described herein and a carrier material. In some embodiments, the polypeptide compositions are bound to the carrier material. In some embodiments, the carrier material comprises calcium phosphate. In some embodiments, the carrier material comprises hydroxyapatite. In some embodiments, the carrier material comprises alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicate, vanadate, and related ceramic minerals, or chelated divalent metal ions, or any combination thereof.

[0023] Also provided herein are methods of treating a subject, the methods comprising delivering to the subject a polypeptide composition described herein or a device described herein. In some embodiments, the polypeptide composition or device is delivered to treat a bone defect in the subject. In some embodiments, at least about 0.5 mg of the polypeptide composition per cc of defect volume is delivered to the subject. In some embodiments, about 0.5 mg to about 10 mg of the polypeptide composition per cc of defect volume is delivered to the subject.

[0024] Also provided herein are methods of delivering a therapeutic agent to an organ or tissue of a subject, the methods comprising delivering to the organ or tissue a carrier material and a therapeutic agent, wherein the therapeutic agent is bound to the carrier material via a targeting polypeptide, the targeting polypeptide comprising: (a) a sequence at least 80% identical to SEQ ID NO:22; (b) a sequence at least 80% identical to SEQ ID NO:402; (c) a sequence at least 80% identical to SEQ ID NO:401; or (d) a sequence at least 80% identical to SEQ ID NO:413 ((X1)(X2)), wherein X1 is (e) a sequence that is at least 80% identical to SEQ ID NO:21, (f) a sequence that is at least 80% identical to SEQ ID NO:414 ((X1)(X2)), wherein X1 comprises SEQ ID NO:2 and X2 comprises SEQ ID NO:6 and SEQ ID NO:7, (g) a sequence that is at least 80% identical to SEQ ID NO:416 ((X1)(X2)), wherein X1 comprises SEQ ID NO:6 and X2 comprises SEQ ID NO:7 and SEQ ID NO:4, (h) a sequence that is at least 80% identical to SEQ ID NO:408 ((X1)(X2)). (i) a sequence at least 80% identical to SEQ ID NO:20, (j) a sequence at least 80% identical to SEQ ID NO:409 ((X1)(X2)), wherein X1 comprises SEQ ID NO:2 and X2 comprises SEQ ID NO:6, (k) a sequence at least 80% identical to SEQ ID NO:411 ((X1)(X2)), wherein X1 comprises SEQ ID NO:6 and X2 comprises SEQ ID NO:7, (l) a sequence at least 80% identical to SEQ ID NO:412 ((X1)(X2)). (m) a sequence at least 80% identical to SEQ ID NO:2 (VIGESTHHRPWS), (n) a sequence at least 80% identical to SEQ ID NO:4 (ILAESTHHKPWT), (o) a sequence at least 80% identical to SEQ ID NO:6 (IIGESSHHKPFT), (p) a sequence at least 80% identical to SEQ ID NO:7 (GLGDTTHHRPWG), or (q) any combination of two or more of (a)-(p). In some embodiments, the carrier material comprises calcium phosphate. In some embodiments, the targeting polypeptide is conjugated to a therapeutic agent. In some embodiments, the therapeutic agent comprises a growth factor. In some embodiments, the therapeutic agent comprises a BMP.In some embodiments, the BMP comprises BMP-2. In some embodiments, the therapeutic agent comprises a sequence at least about 80% identical to SEQ ID NO: 32. In some embodiments, the therapeutic agent comprises a sequence at least about 80% identical to any one of SEQ ID NOs: 46-71, 73-77, 79-101, 152, 168, 176, 268. In some embodiments, the therapeutic agent is delivered to treat a bone defect in a subject. In some embodiments, at least about 0.5 mg of therapeutic agent is delivered per cc of defect volume. In some embodiments, about 0.5 mg to about 10 mg of therapeutic agent is delivered per cc of defect volume.

[0025] Chimeric polypeptides are also provided herein, and the chimeric polypeptides include those having (i) an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to: VIGESTHHRPWS (SEQ ID NO: 2), LIADSTHHSPWT (SEQ ID NO: 3), ILAESTHHKPWT (SEQ ID NO: 4), or an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to ILAETTHHRPWS (SEQ ID NO: 5). an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an amino acid sequence IIGESSHHKPFT (SEQ ID NO: 6); an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an amino acid sequence GLGDTTHHRPWG (SEQ ID NO: 7); an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an amino acid sequence VLGDTTHHKPWT (SEQ ID NO: 8); an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to STADTSHHRPS (SEQ ID NO: 10); an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to TSGGESTHHRPS (SEQ ID NO: 11); an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to TSGGESSHHKPS (SEQ ID NO: 12); an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to RPS (SEQ ID NO: 13), an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GSSGESTHHKPST (SEQ ID NO: 14), an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to VGADSTHHRPVT (SEQ ID NO: 15), an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GAADTTHHRPVT (SEQ ID NO: 16),or 100% identical to, an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to, AGADTTHHRPVT (SEQ ID NO: 17), an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to, GGADTTHHRPAT (SEQ ID NO: 18), and an amino acid sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to, GGADTTHHRPGT (SEQ ID NO: 19); and (ii) a mammalian growth factor.

[0026] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 2. In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 2. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 2.

[0027] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 4. In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 4. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 4.

[0028] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 6. In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 6. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 6.

[0029] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 7. In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 7. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 7.

[0030] In some embodiments, the targeting polypeptide comprises two or more targeting polypeptides. In some embodiments, the two or more targeting polypeptides are about 50, 45, 40, 35, 30, 25, 20, 15, or 10 or fewer targeting polypeptides. In some embodiments, the two or more targeting polypeptides are about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, or 30 targeting polypeptides. In some embodiments, the two or more targeting polypeptides are about 2 to about 10 targeting polypeptides. In some embodiments, the two or more targeting polypeptides are about 5 targeting polypeptides.

[0031] In some embodiments, each adjacent pair of two or more targeting polypeptides are immediately adjacent to one another, hi some embodiments, at least two of the two or more targeting polypeptides are immediately adjacent to one another.

[0032] In some embodiments, each adjacent pair of two or more targeting polypeptides is separated by a linker sequence, hi some embodiments, at least two of the two or more targeting polypeptides are separated by a linker sequence.

[0033] In some embodiments, the targeting polypeptide comprises at least two different polypeptides.

[0034] In some embodiments, the targeting polypeptide comprises two or more copies of the same polypeptide.

[0035] In some embodiments, the targeting polypeptide further comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 1. In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 1. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 1.

[0036] In some embodiments, the targeting polypeptide comprises: (i) a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:1; (ii) a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:2; (iii) a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:4; (iv) a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:6; (v) a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:7; or (vi) any combination of (i)-(v). In some embodiments, the targeting polypeptide comprises (i), (ii), (iii), (iv), and (v). In some embodiments, the targeting polypeptide comprises SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and SEQ ID NO:7. In some embodiments, the targeting polypeptide comprises SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and SEQ ID NO:7.

[0037] In some embodiments, the targeting polypeptide comprises LLADTTHHRPWT (SEQ ID NO: 1) and / or GQVLPTTTPSSP (SEQ ID NO: 44).

[0038] In some embodiments, the targeting polypeptide comprises LLADTTHHRPWT (SEQ ID NO: 1) and / or VIGESTHHRPWS (SEQ ID NO: 2).

[0039] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWTVIGESTHHRPWS (SEQ ID NO: 20). In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 20. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 20.

[0040] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWT (SEQ ID NO: 1), a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to VIGESTHHRPWS (SEQ ID NO: 2), and a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to IIGESSHHKPFT (SEQ ID NO: 6). In some embodiments, the targeting polypeptide comprises a sequence at least 90% identical to SEQ ID NO: 1, a sequence at least 90% identical to SEQ ID NO: 2, and a sequence at least 90% identical to SEQ ID NO: 6. In some embodiments, the targeting polypeptide comprises SEQ ID NOs: 1, 2, and 6.

[0041] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to VIGESTHHRPWS (SEQ ID NO: 2) and a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to IIGESSHHKPFT (SEQ ID NO: 6). In some embodiments, the targeting polypeptide comprises a sequence at least 90% identical to SEQ ID NO: 2 and a sequence at least 90% identical to SEQ ID NO: 6. In some embodiments, the targeting polypeptide comprises SEQ ID NOs: 2 and 6.

[0042] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFT (SEQ ID NO: 21). In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 21. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 21.

[0043] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWG (SEQ ID NO: 401). In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 401. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 401.

[0044] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to VIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWT (SEQ ID NO: 402). In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 402. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 402.

[0045] In some embodiments, targeting polypeptides include LLADTTHHRPWT (SEQ ID NO: 1), VIGESTHHRPWS (SEQ ID NO: 2), IIGESSHHKPFT (SEQ ID NO: 6), GLGDTTHHRPWG (SEQ ID NO: 7), and ILAESTHHKPWT (SEQ ID NO: 4).

[0046] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWT (SEQ ID NO: 22). In some embodiments, the targeting polypeptide comprises a sequence at least about 80% identical to SEQ ID NO: 22. In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 22. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 22.

[0047] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWT (SEQ ID NO: 1) and a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to ILAESTHHKPWT (SEQ ID NO: 4). In some embodiments, the targeting polypeptide comprises a sequence at least 90% identical to SEQ ID NO: 1 and a sequence at least 90% identical to SEQ ID NO: 4. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 1 and SEQ ID NO: 4.

[0048] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWTILAESTHHKPWT (SEQ ID NO: 23).

[0049] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWTILAESTHHKPWTLLADTTHHRPWTILAESTHHKPWTLLADTTHHRPWT (SEQ ID NO: 24).

[0050] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWT (SEQ ID NO: 1) and a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GLGDTTHHRPWG (SEQ ID NO: 7). In some embodiments, the targeting polypeptide comprises a sequence at least about 90% identical to SEQ ID NO: 1 and a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 7. In some embodiments, the targeting polypeptide comprises SEQ ID NO: 1 and SEQ ID NO: 7.

[0051] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWTGLGDTTHHRPWG (SEQ ID NO: 25).

[0052] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRPWT (SEQ ID NO: 26).

[0053] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRPWT (SEQ ID NO: 27).

[0054] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRPWT (SEQ ID NO: 28).

[0055] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to STADTSHHRPS (SEQ ID NO: 10), a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to TSGGESTHHRPS (SEQ ID NO: 11), a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to TSGGESSHHKPS (SEQ ID NO: 12), a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to TGSGDSSHHRPS (SEQ ID NO: 13), and a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GSSGESTHHKPST (SEQ ID NO: 14).

[0056] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to STADTSHHRPSTSGGESTHHRPSTSGGESSHHKPSTGSGDSSHHRPSGSSGESTHHKPST (SEQ ID NO: 29).

[0057] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to VGADSTHHRPVT (SEQ ID NO: 15), a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GAADTTHHRPVT (SEQ ID NO: 16), a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to AGADTTHHRPVT (SEQ ID NO: 17), a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GGADTTHHRPAT (SEQ ID NO: 18), and a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GGADTTHHRPGT (SEQ ID NO: 19).

[0058] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to VGADSTHHRPVTGAADTTHHRPVTAGADTTHHRPVTGGADTTHHRPATGGADTTHHRPGT (SEQ ID NO: 30).

[0059] In some embodiments, the targeting polypeptide is at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to STADTSHHRPS (SEQ ID NO: 10), at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to LLADTTHHRPWT (SEQ ID NO: 1), at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to TSGGESTHHRPS (SEQ ID NO: 11), at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to VGADSTHHRPVT (SEQ ID NO: 15), at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to TSGGESSHHKPS (SEQ ID NO: 12). a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GAADTTHHRPVT (SEQ ID NO: 16), a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to TGSGDSSHHRPS (SEQ ID NO: 13), a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GSSGESTHHKPST (SEQ ID NO: 14), and a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GGADTTHHRPAT (SEQ ID NO: 18).

[0060] In some embodiments, the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to STADTSHHRPSLLADTTHHRPWTTSGGESTHHRPSVGADSTHHRPVTTSGGESSHHKPSGAADTTHHRPVTTGSGDSSHHRPSGSSGESTHHKPSTGGADTTHHRPAT (SEQ ID NO: 31).

[0061] In some embodiments, the targeting polypeptide comprises the amino acid sequence of Formula I: A0B0C0D0E0F0G0H0I0J0K0L0 (Formula I) (SEQ ID NO: 35), where A0 is V, L, I, G, S, T, or A, B0 is I, L, V, Q, T, S, G, or A, C0 is G, A, V, or S, D0 is E, D, L, or G, E0 is S, T, PT, E, or D, F0 is T or S, G0 is H, T, or S, H0 is H or T, I0 is R, S, K, P, or H, J0 is P, S, R, or K, K0 is W, F, S, P, V, A, or G, and L0 is absent or S, T, G, (or A). In some embodiments, Formula I does not include LLADTTHHRPWT (SEQ ID NO: 1).

[0062] In some embodiments, the targeting polypeptide comprises two or more amino acid sequences having Formula I. In some embodiments, at least two of the two or more amino acid sequences are different. In some embodiments, at least two or more of the amino acid sequences are the same. In some embodiments, the two or more is about 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0063] In some embodiments, at least two of the two or more amino acid sequences having Formula I are immediately adjacent to each other. In some embodiments, each of the two or more amino acid sequences having Formula I is immediately adjacent to each other.

[0064] In some embodiments, at least two of the two or more amino acid sequences having Formula I are separated by a linker sequence. In some embodiments, each of the two or more amino acid sequences having Formula I is separated by a linker sequence.

[0065] In some embodiments of any of the chimeric polypeptides described herein, the mammalian growth factor is selected from the group consisting of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-I), fibroblast growth factor (FGF), fibroblast growth factor 2 (FGF2), fibroblast growth factor 18 (FGF18), transforming growth factor alpha (TGF-α), transforming growth factor beta (TGF-β), transforming growth factor beta-1 (TGF-β1), transforming growth factor beta 3 (TGF-β3), osteogenic protein 1 (OP-1), osteogenic protein 1 (O-P ... P-2), osteogenic protein 3 (OP-3), bone morphogenetic protein 2 (BMP-2), bone morphogenetic protein 3 (BMP-3), bone morphogenetic protein 4 (BMP-4), bone morphogenetic protein 5 (BMP-5), bone morphogenetic protein 6 (BMP-6), bone morphogenetic protein 7 (BMP-7), bone morphogenetic protein 9 (BMP-9), bone morphogenetic protein 10 (BMP-10), bone morphogenetic protein 11 (BMP-11), bone morphogenetic protein 12 (BMP-12), bone morphogenetic protein (BMP-13), bone morphogenetic protein (BMP-15), dentin phosphoprotein (DPP), plant-related Growth differentiation factor (Vgr), growth differentiation factor 1 (GDF-1), growth differentiation factor 3 (GDF-3), growth differentiation factor 5 (GDF-5), growth differentiation factor 6 (GDF-6), growth differentiation factor 7 (GDF-7), growth differentiation factor 8 (GDF8), growth differentiation factor 11 (GDF11), growth differentiation factor 15 (GDF15), vascular endothelial growth factor (VEGF), hyaluronic acid-binding protein (HABP), collagen-binding protein (CBP), fibroblast growth factor 18 (FGF-18), keratinocyte growth factor (KGF), tumor necrosis factor α (TNFα), tumor necrosis factor (TNF)-related apoptosis factor (AAP) Pathogenesis-inducing ligand (TRAIL), wnt family member 1 (WNT1), wnt family member 2 (WNT2), wnt family member 2B (WNT2B), wnt family member 3 (WNT3), wnt family member 3A (WNT3A), wnt family member 4 (WNT4), wnt family member 5A (WNT5A), wnt family member 5B (WNT5B), wnt family member 6 (WNT6), wnt family member 7A (WNT7A), wnt family member 7B (WNT7B),and one or more of wnt family member 8A (WNT8A), wnt family member 8B (WNT8B), wnt family member 9A (WNT9A), wnt family member 9B (WNT9B), wnt family member 10A (WNT10A), wnt family member 10B (WNT10B), wnt family member 11 (WNT11), neuregulin 1 (NRG1), or wnt family member 16 (WNT16).

[0066] In some embodiments of any of the chimeric polypeptides described herein, the mammalian growth factor is selected from the group consisting of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-I), fibroblast growth factor (FGF), fibroblast growth factor 2 (FGF2), fibroblast growth factor 18 (FGF18), transforming growth factor alpha (TGF-α), transforming growth factor beta (TGF-β), transforming growth factor beta-1 (TGF-β1), transforming growth factor beta 3 (TGF-β3), osteogenic protein 1 (OP-1), osteogenic protein 1 (O-P ... P-2), osteogenic protein 3 (OP-3), bone morphogenetic protein 2 (BMP-2), bone morphogenetic protein 3 (BMP-3), bone morphogenetic protein 4 (BMP-4), bone morphogenetic protein 5 (BMP-5), bone morphogenetic protein 6 (BMP-6), bone morphogenetic protein 7 (BMP-7), bone morphogenetic protein 9 (BMP-9), bone morphogenetic protein 10 (BMP-10), bone morphogenetic protein 11 (BMP-11), bone morphogenetic protein 12 (BMP-12), bone morphogenetic protein (BMP-13), bone morphogenetic protein (BMP-15), dentin phosphoprotein (DPP), plant-related Growth differentiation factor (Vgr), growth differentiation factor 1 (GDF-1), growth differentiation factor 3 (GDF-3), growth differentiation factor 5 (GDF-5), growth differentiation factor 6 (GDF-6), growth differentiation factor 7 (GDF-7), growth differentiation factor 8 (GDF8), growth differentiation factor 11 (GDF11), growth differentiation factor 15 (GDF15), vascular endothelial growth factor (VEGF), hyaluronic acid-binding protein (HABP), collagen-binding protein (CBP), fibroblast growth factor 18 (FGF-18), keratinocyte growth factor (KGF), tumor necrosis factor α (TNFα), tumor necrosis factor (TNF)-related apoptosis factor (AAP) Pathogenesis-inducing ligand (TRAIL), wnt family member 1 (WNT1), wnt family member 2 (WNT2), wnt family member 2B (WNT2B), wnt family member 3 (WNT3), wnt family member 3A (WNT3A), wnt family member 4 (WNT4), wnt family member 5A (WNT5A), wnt family member 5B (WNT5B), wnt family member 6 (WNT6), wnt family member 7A (WNT7A), wnt family member 7B (WNT7B),The present invention also includes one or more functional portions of wnt family member 8A (WNT8A), wnt family member 8B (WNT8B), wnt family member 9A (WNT9A), wnt family member 9B (WNT9B), wnt family member 10A (WNT10A), wnt family member 10B (WNT10B), wnt family member 11 (WNT11), neuregulin 1 (NRG1), or wnt family member 16 (WNT16).

[0067] In some embodiments, the mammalian growth factor comprises BMP-2. In some embodiments, the mammalian growth factor comprises a functional portion of BMP-2. In some embodiments, the mammalian growth factor comprises a mature BMP-2 peptide without a signal sequence. In some embodiments, the functional portion of BMP-2 comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR (SEQ ID NO: 32). In some embodiments, the mammalian growth factor comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a sequence of Table B. In some embodiments, the mammalian growth factor comprises a sequence at least about 90% identical to SEQ ID NO: 32. In some embodiments, the mammalian growth factor comprises SEQ ID NO:32.

[0068] In some embodiments, the chimeric polypeptide comprises (a) a sequence comprising (i) a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 1; (ii) a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 2; or (iii) a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 4. (iv) a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:6; (v) a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:7; or (vi) any combination of (i)-(v); and (b) a mammalian growth factor comprising a functional portion of BMP-2. In some embodiments, the functional portion of BMP-2 comprises SEQ ID NO:32. In some embodiments, the chimeric polypeptide comprises a targeting polypeptide comprising SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and SEQ ID NO:7, and a mammalian growth factor comprising SEQ ID NO:32. In some embodiments, the targeting polypeptide and the mammalian growth factor are connected via a linker polypeptide.

[0069] In some embodiments, the chimeric polypeptide comprises a targeting polypeptide comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 402, and a mammalian growth factor comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some embodiments, the chimeric polypeptide comprises a targeting polypeptide comprising a sequence at least about 90% identical to SEQ ID NO: 402, and a mammalian growth factor comprising a sequence at least about 90% identical to SEQ ID NO: 32. In some embodiments, the targeting polypeptide and the mammalian growth factor are connected via a linker polypeptide.

[0070] In some embodiments, the chimeric polypeptide comprises a targeting polypeptide comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 22, and a mammalian growth factor comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some embodiments, the chimeric polypeptide comprises a targeting polypeptide comprising a sequence at least about 90% identical to SEQ ID NO: 22, and a mammalian growth factor comprising a sequence at least about 90% identical to SEQ ID NO: 32. In some embodiments, the targeting polypeptide and the mammalian growth factor are connected via a linker polypeptide.

[0071] In some embodiments of any of the chimeric polypeptides described herein, the chimeric polypeptide further comprises a linker sequence, hi some embodiments, the linker sequence connects the targeting polypeptide and the mammalian growth factor.

[0072] In some embodiments, the linker sequence comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to TGGSGEGGTGASTGGSAGTGGSGGTTSGEAGGSSGAG (SEQ ID NO: 33).

[0073] In some embodiments, the linker sequence comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to GAGTG (SEQ ID NO: 34).

[0074] In some embodiments, the chimeric polypeptide comprises a flexible linker comprising a sequence of about 5 to about 50 amino acids, wherein at least about 5 of the amino acids do not have a regular secondary structure. In some embodiments, the regular secondary structure comprises any helical structure, such as an alpha helix, a 3' helix, or a pi helix, a beta turn, an omega loop, and / or a beta sheet. In some embodiments, the flexible linker comprises at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% glycine, alanine, and serine, glycine, alanine, glycine, serine, alanine, serine, or glycine, alanine, and serine. In some embodiments, the linker comprises 1, 2, 3, 4, or 5 GSEG (SEQ ID NO: 702). In some embodiments, the linker comprises 1, 2, 3, 4, or 5 SEGG (SEQ ID NO: 703).

[0075] In some embodiments, the chimeric polypeptide comprises a linker sequence that is at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to ASGAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTG (SEQ ID NO: 701). In some embodiments, the linker comprises a sequence that is at least about 90% identical to SEQ ID NO: 701. In some embodiments, the linker comprises SEQ ID NO: 701.

[0076] In some embodiments, the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to MPIGSLLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWTASGAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTGQAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR (SEQ ID NO:502). In some embodiments, the chimeric polypeptide comprises a sequence at least about 90% identical to SEQ ID NO:502. In some embodiments, the chimeric polypeptide comprises a sequence at least about 91% identical to SEQ ID NO:502. In some embodiments, the chimeric polypeptide comprises a sequence at least about 92% identical to SEQ ID NO:502. In some embodiments, the chimeric polypeptide comprises a sequence at least about 93% identical to SEQ ID NO:502. In some embodiments, the chimeric polypeptide comprises a sequence at least about 94% identical to SEQ ID NO:502. In some embodiments, the chimeric polypeptide comprises a sequence at least about 95% identical to SEQ ID NO:502. In some embodiments, the chimeric polypeptide comprises a sequence at least about 96% identical to SEQ ID NO:502. In some embodiments, the chimeric polypeptide comprises a sequence at least about 97% identical to SEQ ID NO:502. In some embodiments, the chimeric polypeptide comprises a sequence at least about 98% identical to SEQ ID NO:502. In some embodiments, the chimeric polypeptide comprises a sequence at least about 99% identical to SEQ ID NO:502. In some embodiments, the chimeric polypeptide comprises SEQ ID NO:502.

[0077] In some embodiments of any of the chimeric polypeptides described herein, the chimeric polypeptide is bound to a carrier material. In some embodiments, the targeting polypeptide is bound to a carrier material. In some embodiments, the carrier material comprises calcium phosphate. In some embodiments, the carrier material comprises β-TCP. In some embodiments, the carrier material comprises hydroxyapatite. In some embodiments, the targeting polypeptide is bound to the carrier material with a KD of about 1 picomolar to about 100 micromolar. In some embodiments, the targeting polypeptide is bound to β-TCP with a KD of about 1 picomolar to about 100 micromolar. In some embodiments, the KD is measured using any method known in the art and / or described herein.

[0078] Also provided herein are compositions comprising any one of the chimeric polypeptides described herein.

[0079] In some embodiments, the composition comprises a carrier material. In some embodiments, the carrier material comprises calcium phosphate. In some embodiments, the carrier material comprises β-TCP. In some embodiments, the carrier material comprises hydroxyapatite. In some embodiments, the carrier material is formulated as a powder, putty, or paste. In some embodiments, the carrier material comprises a scaffold, fiber, mesh, or sponge.

[0080] In some embodiments of any of the compositions described herein, the composition is a pharmaceutical composition.

[0081] Additionally, kits comprising any of the polypeptides, carrier materials, and / or compositions described herein are provided herein.

[0082] Also provided herein are targeting polypeptides of any of the chimeric polypeptides described herein.

[0083] Also provided herein are methods for promoting bone or cartilage formation in a subject in need thereof, said methods comprising administering to the subject a therapeutically effective amount of any of the polypeptides and / or compositions described herein.

[0084] Also provided herein are methods for replacing and / or repairing bone or cartilage in a subject in need thereof, said methods comprising administering to the subject a therapeutically effective amount of any of the polypeptides and / or compositions described herein.

[0085] Also provided herein are methods for treating fracture or bone loss in a subject in need thereof, said methods comprising administering to the subject a therapeutically effective amount of any of the polypeptides and / or compositions described herein.

[0086] In some embodiments of any of the methods described herein, the subject has a bone fracture. In some embodiments of any of the methods described herein, the subject has a bone defect. In some embodiments of any of the methods described herein, the subject has a cartilage tear or cartilage defect. In some embodiments of any of the methods described herein, the subject has a cartilage defect.

[0087] As used herein, the term "subject" refers to any mammal. Thus, a subject may refer to, for example, a mouse, rat, dog, cat, horse, cow, pig, guinea pig, rat, human, monkey, etc. If the subject is a human, the subject may be referred to herein as a patient. In some embodiments, the subject or "subject in need of treatment" may be a canine (e.g., a dog), a feline (e.g., a cat), an equine (e.g., a horse), a sheep, a cow, a pig, a goat, a primate, such as a monkey (e.g., a marmoset, a baboon), or an ape (e.g., a gorilla, a chimpanzee, an orangutan, or a gibbon), a human, or a rodent (e.g., a mouse, a guinea pig, a hamster, or a rat). In some embodiments, the subject or "subject in need of treatment" may be a mammal other than a human, particularly a mammal traditionally used as a model for demonstrating therapeutic efficacy in humans (e.g., a murine, a lagomorph, a porcine, a canine, or a primate).

[0088] In some embodiments, the term "therapeutically effective amount" refers to an amount of a polypeptide or composition effective to "treat" a disease, illness, or condition in a subject. In some cases, a therapeutically effective amount of a polypeptide or composition reduces the severity of symptoms of the disease, illness, or disorder. In some instances, the disease, illness, or disorder involves organ or tissue deficiency.

[0089] "Affinity" refers to the strength of the total non-covalent interactions between a β-TCP binding sequence (or a chimeric polypeptide or polypeptide comprising a β-TCP binding sequence) and its binding partner (e.g., β-TCP). Affinity can be measured by common methods known in the art, including those described herein. Affinity can be determined, for example, using surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®). Additional methods for determining affinity are known in the art.

[0090] The percent (%) sequence identity to a reference polypeptide sequence is the percentage of amino acid residues in a candidate sequence that are identical to those in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and does not consider any conservative substitutions as part of the sequence identity. Alignment for the purpose of determining percent amino acid sequence identity can be achieved in a variety of known ways, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Appropriate parameters for aligning sequences can be determined, including the algorithm required to achieve maximum alignment across the entire length of the sequences being compared. However, for purposes herein, the % amino acid sequence identity value is generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was created by Genentech, Inc., and its source code, together with user documentation, has been submitted to the U.S. Copyright Office (Washington, DC, 20559) and is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc. (South San Francisco, Calif.) or can be compiled from the source code. The ALIGN-2 program must be compiled for use on UNIX operating systems, including Digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.

[0091] In situations where ALIGN-2 is used for amino acid sequence comparison, the % amino acid sequence identity of a given amino acid sequence A to a given amino acid sequence B (which may alternatively be expressed as a given amino acid sequence A having or containing % amino acid sequence identity to given amino acid sequence B) is calculated as follows: 100 × fraction X / Y, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It should be understood that if the length of amino acid sequence A is not equal to the length of amino acid sequence B, then the % amino acid sequence identity of A to B will not be equal to the % amino acid sequence identity of B to A. Unless otherwise specified, all % amino acid sequence identity values ​​used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[0092] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. Methods and materials are described herein for use in the present invention, but other suitable methods and materials known in the art can also be used. Materials, methods, and examples are illustrative only and are not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In the event of a conflict, the present specification, including definitions, will control.

[0093] Other features and advantages of the invention will become apparent from the following detailed description and drawings, and from the claims. [Brief explanation of the drawings]

[0094] [Figure 1A] 1 is a representative in vivo radiograph (lateral-medial orientation) of an animal from experimental group A. [Figure 1B]10 is a representative in vivo radiograph (lateral-medial orientation) of an animal from experimental group B. [Figure 1C] 10 is a representative in vivo radiograph (lateral-medial orientation) of an animal from experimental group C. [Figure 2] Representative graphs of the mean radiographic scores (+SEM, n=9-10) of animals from each group at 4 and 8 weeks postoperatively (for each group A-C, the left bar is week 4 and the right bar is week 8). *P<0.01 vs. group Cl, # P<0.01 vs. group, ┼P<0.01 vs. group C at week 4. [Figure 3A] Representative radiographs, sagittal, and transverse micro-CT images from animals in groups A, B, or C at 4 weeks post-surgery. [Figure 3B] Representative radiographs, sagittal, and transverse micro-CT images from animals in groups A, B, or C at 4 weeks post-surgery. [Figure 4] Schematic representation of callus formation changes in animals from Groups A, B, or C at 4 weeks post-surgery. The red shaded area is an approximation of the mineralized callus volume. [Figure 5A] Representative graphs of micro-CT analysis showing total callus volume in bone specimens obtained at 8 weeks post-surgery from animals in groups A (n = 9), B (n = 7), or C (n = 8). Data are expressed as mean ± SEM; *P < 0.01 vs. B, # P < 0.01 vs. C. [Figure 5B] Representative graphs of micro-CT analysis showing bone mineral volume in bone specimens obtained at 8 weeks post-surgery from animals in groups A (n=9), B (n=7), or C (n=8). Data are expressed as mean ± SEM; *P<0.01 vs. B, #P<0.01 vs. C. [Figure 6A] Representative graphs of microCT analysis of diaphyseal volume of bone specimens obtained 4 weeks postoperatively in animals from groups A (n=10), B (n=8), or C (n=7). Bone mineral volume is expressed as the percentage of bone mineral volume relative to total volume. Data are expressed as mean ± SEM; *P<0.05 vs. B, #P<0.05 vs. C. A1 vs. B1, p=0.059. [Figure 6B] Representative graphs of micro-CT analysis of cortical bone volume in bone specimens obtained 4 weeks postoperatively in animals from groups A (n=10), B (n=8), or C (n=7). Bone mineral volume is expressed as the percentage of bone mineral volume relative to total volume. Data are expressed as mean ± SEM; *P<0.05 vs. B, #P<0.05 vs. C. [Figure 7A] Representative graphs of microCT analysis of total callus volume in bone specimens obtained at 8 weeks postoperatively from animals in groups A (n = 9), B (n = 7), or C (n = 8). Data are expressed as mean ± SEM; *P < 0.01 vs. B, # P < 0.01 vs. C. [Figure 7B] Representative graphs of microCT analysis of bone mineral volume in bone specimens obtained at 8 weeks postoperatively from animals in groups A (n = 9), B (n = 7), or C (n = 8). Data are expressed as mean ± SEM; *P < 0.01 vs. B, # P < 0.01 vs. C. [Figure 8] Representative graphs of limit load to failure (ULF) at 4 and 8 weeks postoperatively for animals in groups A, B, or C (for each group A-C, the left bar is 4 weeks, and the right bar is 8 weeks). Data are expressed as mean + / - SEM. *P<0.05 vs. 4-week group, #P<0.01 vs. 8-week group. [Figure 9A] Representative histological images of Von Kossa and H&E stained bone specimens obtained from animals in Groups A, B, or C at 4 weeks post-surgery. [Figure 9B] Representative histological images of TRAP+ osteoclast-stained bone specimens obtained at 4 weeks post-surgery from animals in groups A, B, or C (left, middle, and right panels, respectively). White arrows indicate osteoclasts, and yellow arrows indicate osteocytes. [Figure 10A] Representative histological images of Von Kossa and H&E stained bone specimens obtained from animals in Groups A, B, or C at 8 weeks post-surgery. [Figure 10B]Representative histological images of TRAP+ osteoclast-stained bone specimens obtained 8 weeks post-surgery from animals in groups A, B, or C (left, middle, and right panels, respectively). White arrows indicate osteoclasts, and yellow arrows indicate osteocytes. [Figure 11] Representative immunoblot of MCF-7 cell lysates probed with anti-P-Akt antibody, and MCF-7 cells were incubated with β-TCBP-HRG. [Figure 12] Representative immunoblot of MCF-7 lysates probed with anti-P-Akt antibody, and MCF-7 cells were incubated with β-TCBP-HRG (free) or β-TCBP-HRG (β-TCP-bound). [Figure 13] The procedure for creating a tibial defect in goats as described in Example 6 is outlined below. [Figure 14A] 10 is a mean radius BV and mean moment angle plot showing the pattern and extent of new bone mineralization at the defect site for each treatment group. [Figure 14B] Total bone volume plots in a 2.5 cm central region and a 5 cm complete defect region. Variation in total new bone volume between goats within treatment groups was measured. At the medium and high doses, tBMP-2 demonstrated comparable bone formation, superior to the low dose and substrate-only groups. For each group, A-D, the left bar corresponds to the 2.5 cm central region, and the right bar corresponds to the 5 cm region. [Figure 14C]Dose-response model fit curves using nonlinear least-squares regression constructed based on bone mass data (red dots) from the 2.5 cm central region. The solid blue central line is the dose-response model fit. The three orange dots, from bottom to top, identify the model-estimated doses at which 50%, 75%, and 90% of the maximum effect is achieved on a logarithmic scale. The orange lines are the 75% confidence intervals for such doses. Dose-response analysis showed a statistically significant effect of tBMP-2 dose on total bone mass generated in the 2.5 cm central region (p=0.0003). The model curves show that, ranging from "no dose" to "low dose" (=2.14 mg / cc), the initial response increases rapidly with dose, then becomes more gradual as it plateaus. Beyond the 2.14 mg / cc dose, increasing the dose of tBMP-2 to achieve higher bone mass appears to have little additional effect (the dose-response curve plateaus). A dose of 2 mg / cc of defect volume is sufficient to achieve a complete response. [Figure 14D] Ranking of postmortem radiographs (AP and ML views) of 22 tibial defects. Higher rank numbers indicate greater bone formation in the tibial defects (1 = complete bone healing to 22 = no healing). In the control and low-dose groups, little bone formed at the defect site. In the high- and medium-dose tBMP-2 groups, robust bone formation with some bone bridging was observed (9 of 15 goats). The high- and medium-dose groups resulted in significantly greater new bone formation at the defect site compared to the other groups ("A" and "B"). [Figure 15] The procedure for creating and treating tibial defects in sheep as described in Example 7 is outlined. [Figure 16A] 10A-10C are representative radiographs from each month of the study described in Example 7 in the treatment group receiving 2 mg of tBMP-2 per cc of defect volume. [Figure 16B]1 is a graph of mean ± standard deviation bone mass measured from CT images for the study described in Example 7. For each week of treatment, the bars from left to right (dark to light shading) represent 2 mg / cc tBMP2, 5 mg / cc tBMP2, and autograft control. [Figure 16C] Representative radiographs (AP and ML views) of tibial defects in all conditions. The 2 mg / cc dose group produced significant bone growth, as did the 5 mg / cc and control conditions. Results were generally consistent across sheep tested. [Figure 16D] Representative H&E histology images from the 2 mg / cc group at week 8 showing normal bone formation adjacent to the cut edge of the original cortex. Arrows indicate the cortex (blue, upper right arrow), connective tissue (black, lower right arrow), and cartilage tissue (gray, lower left arrow), as well as new bone growth (green, upper left arrow). [Figure 16E] Tetrachrome histology image from the 2 mg / cc group. At 8 weeks, residual polymer fibers are visible, some surrounded by new bone growth and some surrounded by connective tissue with multinucleated giant cells associated with the biologic breakdown of the fibers. DETAILED DESCRIPTION OF THE INVENTION

[0095] Provided herein are polypeptides for targeted delivery of therapeutic agents to a region of interest, including a defect. In some embodiments, the region includes bone, and the therapeutic agent is delivered to treat the bone defect. In some embodiments, the polypeptide is a targeting polypeptide comprising one or more of the polypeptides in Table A.

[0096] In some embodiments, the targeting polypeptide comprises Formula I: A0B0C0D0E0F0G0H0I0J0K0L0 (Formula I) (SEQ ID NO:35), where A0 is V, L, I, G, S, T, or A, B0 is I, L, V, Q, T, S, G, or A, C0 is G, A, V, or S, D0 is E, D, L, or G, E0 is S, T, PT, E, or D, F0 is T or S, G0 is H, T, or S, H0 is H or T, I0 is R, S, K, P, or H, J0 is P, S, R, or K, K0 is W, F, S, P, V, A, or G, and L0 is absent or S, T, G, (or A). In some embodiments, Formula I does not comprise LLADTTHHRPWT (SEQ ID NO:1).

[0097] Provided herein are chimeric polypeptides comprising a targeting polypeptide and a therapeutic agent. In some embodiments, the therapeutic agent comprises one or more of the polypeptides in Table B. In some embodiments, any of the targeting polypeptides and / or chimeric polypeptides described herein can be bound to one or more substrates comprising βTCP (e.g., Master Graft Strip, Vitoss Foam Pack, chronOS Strip, Vitoss Micromorsels, LifeInk500, Hyperelastic Bone, bioactive glass, βTCP powder, βTCP spray-dried powder, hydroxyapatite powder, hydroxyapatite-coated bone screws, βTCP granules, hydroxyapatite granules, and REBOSSIS). In some embodiments, any of the targeting polypeptides and / or chimeric polypeptides described herein can be bound to silicon nitride or a substrate comprising silicon nitride.

[0098] Also provided herein is a composition comprising any of the targeting polypeptides and / or chimeric polypeptides described herein.In some embodiments, the composition further comprises a substrate comprising βTCP (e.g., Mastergraft Strip, Vitoss Foam Pack, chronOS Strip, Vitoss Micromorsels, LifeInk500, Hyperelastic Bone, bioactive glass, βTCP powder, βTCP spray-dried powder, hydroxyapatite powder, hydroxyapatite-coated bone screw, βTCP granules, hydroxyapatite granules, and REBOSSIS).In some embodiments, the composition further comprises a substrate comprising silicon nitride.

[0099] Also provided herein are kits containing any of these compositions. Also provided are methods for promoting bone or cartilage formation in a subject, methods for replacing and / or repairing bone or cartilage in a subject, and methods for treating fractures or bone loss in a subject, comprising administering any of the compositions described herein to the subject.

[0100] Non-limiting aspects of these polypeptides, compositions, kits, and methods are described below and can be used in any combination without limitation. Additional aspects of these polypeptides, compositions, kits, and methods are known in the art.

[0101] Chimeric Polypeptides In one aspect, provided herein are chimeric polypeptides comprising a targeting polypeptide (e.g., a polypeptide capable of binding to a carrier material) and a therapeutic agent. As used herein, the term "chimeric polypeptide" is interchangeable with "fusion protein," "polypeptide composition," and the like. In some examples, the therapeutic agent comprises one or more of the peptides of Table B, or a functional portion thereof. In some examples, the chimeric polypeptide comprises a targeting polypeptide comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to one or more of SEQ ID NOs: 1-43 or 401-422. In some embodiments, the targeting polypeptide comprises Formula I. In some embodiments, the targeting polypeptide comprises two or more targeting polypeptides. In some embodiments, the two or more targeting polypeptides are no more than about 50, 45, 40, 35, 30, 25, 20, 15, or 10 targeting polypeptides. In some embodiments, the two or more targeting polypeptides are about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, or 30 targeting polypeptides. In some embodiments, the two or more targeting polypeptides are about 2 to about 10 targeting polypeptides. In some embodiments, the two or more targeting polypeptides are about 5 targeting polypeptides.

[0102] In some examples, the targeting polypeptide of the chimeric polypeptide comprises Formula I: A0B0C0D0E0F0G0H0I0J0K0L0 (Formula I) (SEQ ID NO: 35), where A0 is V, L, I, G, S, T, or A, B0 is I, L, V, Q, T, S, G, or A, C0 is G, A, V, or S, D0 is E, D, L, or G, E0 is S, T, PT, E, or D, F0 is T or S, G0 is H, T, or S, H0 is H or T, I0 is R, S, K, P, or H, J0 is P, S, R, or K, K0 is W, F, S, P, V, A, or G, and L0 is absent, S, T, G, or A.

[0103] Non-limiting examples of targeting polypeptides that may be present in any of the chimeric polypeptides described herein are listed in Table A below.

[0104] [Table 1-1]

[0105] [Table 1-2]

[0106] [Table 2-1]

[0107] [Table 2-2]

[0108] [Table 2-3]

[0109] [Table 2-4]

[0110] [Table 2-5]

[0111] [Table 2-6]

[0112] [Table 2-7]

[0113] [Table 2-8]

[0114] [Table 2-9]

[0115] [Table 2-10]

[0116] [Table 2-11]

[0117] In some embodiments, any of the chimeric polypeptides described herein comprises one or more targeting polypeptides. In some embodiments, the chimeric polypeptide comprises 1 to about 10 targeting polypeptides. For example, the chimeric polypeptide comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 targeting polypeptides. In some embodiments, the targeting polypeptide comprises one or more polypeptides that are bound to a carrier material. In some embodiments, the one or more polypeptides are about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 polypeptides. In some embodiments, the targeting polypeptide comprises about 10 to about 100, about 10 to about 90, about 10 to about 80, about 10 to about 70, about 10 to about 60, about 10 to about 50, about 10 to about 40, about 10 to about 30, about 20 to about 100, about 20 to about 90, about 20 to about 80, about 20 to about 70, about 20 to about 60, about 20 to about 50, about 20 to about 40, or about 30 to about 80 amino acids.

[0118] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 1. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0119] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO:2. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0120] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO:3. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0121] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO:4. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0122] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO:5. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0123] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO:6. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0124] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 7. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0125] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 8. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0126] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO:9. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0127] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 10. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0128] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 11. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0129] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 12. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0130] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 13. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0131] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 14. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0132] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 15. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0133] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 16. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0134] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 17. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0135] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 18. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0136] In some embodiments, the chimeric polypeptide comprises an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NO: 19. In some embodiments, the chimeric polypeptide comprises one or more therapeutic agents of Table B, or a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a therapeutic agent of Table B. As a non-limiting example, a therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Also provided in some embodiments are methods of treating organ and / or tissue defects comprising administering the chimeric polypeptides and / or compositions to a subject in need thereof.

[0137] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 501. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 501. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0138] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 502. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 502. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0139] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 503. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 503. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0140] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 504. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 504. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0141] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 505. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 505. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0142] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 506. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 506. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0143] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 507. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 507. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0144] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 508, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 508. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0145] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 509, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 509. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0146] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 510, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 510. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0147] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 511, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 511. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0148] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 512, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 512. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0149] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 513, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 513. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0150] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 514, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 514. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0151] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 515, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 515. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0152] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 516, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 516. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0153] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 517, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 517. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0154] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 518, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 518. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0155] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 519, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 519. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0156] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 520, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 520. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0157] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 521, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 521. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0158] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 522, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 522. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0159] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 523, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 523. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0160] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 524, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 524. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0161] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 525, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 525. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0162] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 526, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 526. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0163] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 527, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 527. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0164] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 528, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 528. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0165] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 529, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 529. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0166] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 530, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 530. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0167] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 531, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 531. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0168] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 532, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 532. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0169] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 533, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 533. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0170] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 534, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 534. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0171] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 535, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 535. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0172] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 536, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 536. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0173] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 537, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 537. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0174] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 538, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 538. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0175] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 539, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 539. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0176] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 540, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 540. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0177] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 541, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 541. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0178] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 542, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 542. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0179] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 543, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 543. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0180] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 544, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 544. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0181] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 545, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 545. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0182] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 546, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 546. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0183] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 547, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 547. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0184] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 548, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 548. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0185] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 549, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 549. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0186] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 550, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 550. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0187] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 551, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 551. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0188] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 552, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 552. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0189] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 553, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 553. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0190] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 554, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 554. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0191] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 555, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 555. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0192] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 556, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 556. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0193] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 557, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 557. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0194] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 558, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 558. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0195] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 559, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 559. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0196] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 560, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 560. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0197] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 561, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 561. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0198] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 562, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 562. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0199] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 563, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 563. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0200] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 564, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 564. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0201] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 565, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 565. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0202] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 566, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 566. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0203] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 567, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 567. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0204] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 568, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 568. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0205] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 569, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 569. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0206] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 570, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 570. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0207] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 571, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 571. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0208] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 572, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 572. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0209] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 573, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 573. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0210] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 574, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 574. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0211] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 575, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 575. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0212] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 576, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 576. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0213] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 577, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 577. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0214] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 578, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 578. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0215] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 579, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 579. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0216] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 580, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 580. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0217] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 581, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 581. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0218] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 582, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 582. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0219] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 583, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 583. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0220] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 584, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 584. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0221] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 585, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 585. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0222] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 586, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 586. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0223] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 587, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 587. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0224] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 588, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 588. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0225] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 589, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 589. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0226] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 590, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 590. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0227] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 591, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 591. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0228] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 592, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 592. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0229] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 593, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 593. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0230] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 594, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 594. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0231] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 595, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 595. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0232] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 596, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 596. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0233] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 597, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 597. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0234] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 598, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 598. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0235] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 599, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 599. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0236] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 600, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 600. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0237] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 601, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 601. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0238] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 602, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 602. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0239] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 603, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 603. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0240] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 604, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 604. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0241] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 605, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 605. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0242] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 606, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 606. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0243] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 607, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 607. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0244] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 608, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 608. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0245] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 609, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 609. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0246] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 610, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 610. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0247] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 611, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 611. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0248] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 612, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 612. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0249] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 613, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 613. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0250] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 614, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 614. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0251] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 615, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 615. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0252] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 616, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 616. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0253] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 617, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 617. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0254] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 618, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 618. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0255] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 619, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 619. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0256] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 620, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 620. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0257] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 621, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 621. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0258] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 622, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 622. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0259] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 623, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 623. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0260] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 624, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 624. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0261] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 625, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 625. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0262] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 626, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 626. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0263] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 627, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 627. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0264] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 628, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 628. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0265] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 629, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 629. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0266] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 630, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 630. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0267] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 631, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 631. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0268] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 632, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 632. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0269] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 633, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 633. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0270] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 634, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 634. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0271] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 635, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 635. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0272] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 636, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 636. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0273] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 637, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 637. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0274] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 638, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 638. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0275] In some embodiments, the chimeric polypeptide comprises a sequence at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 639, wherein the chimeric polypeptide comprises X. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 639. In some aspects, compositions comprising the chimeric polypeptide and a carrier material, e.g., a carrier material provided herein, are also provided. Non-limiting exemplary carrier materials may include one or more of the following: tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), e.g., silicate, vanadate, and related ceramic minerals, and chelated divalent metal ions. In some aspects, methods of treating organ and / or tissue defects are also provided, comprising administering the chimeric polypeptide and / or composition to a subject in need thereof.

[0276] In some embodiments, the chimeric polypeptide further comprises a linker sequence between the two targeting polypeptides, hi some embodiments, the chimeric polypeptide further comprises a linker sequence between the targeting polypeptide and the therapeutic agent.

[0277] In some embodiments, the chimeric polypeptide comprises a signal sequence at its N-terminus. In some embodiments, the chimeric polypeptide comprises a tag sequence (e.g., a poly-His tag, chitin-binding protein (CBP), maltose-binding protein (MBP), strep-tag, glutathione-S-transferase (GST), thioredoxin, or Fc region). Additional examples of tags are known in the art.

[0278] In some embodiments, the chimeric polypeptide comprises a lead sequence at its N-terminus that can aid in expression of the polypeptide. As a non-limiting example, the lead sequence comprises MPIGS (SEQ ID NO: 704).

[0279] Non-limiting exemplary embodiments of chimeric polypeptides are provided herein. (1) In a first embodiment, the chimeric polypeptide comprises a targeting polypeptide. (2) The chimeric polypeptide of embodiment 1, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 1. (3) The chimeric polypeptide of embodiment 1, wherein the targeting polypeptide comprises SEQ ID NO: 1. (4) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 2. (5) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 2. (6) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 3. (7) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 3. (8) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 4. (9) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 4. (10) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 5. (11) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 5. (12) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 6. (13) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 6. (14) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 7. (15) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 7.(16) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 8. (17) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 8. (18) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 9. (19) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 9. (20) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 10. (21) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 10. (22) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 11. (23) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 11. (24) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 12. (25) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 12. (26) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 13. (27) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 13. (28) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 14. (29) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 14.(30) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 15. (31) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 15. (32) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 16. (33) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 16. (34) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 17. (35) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 17. (36) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 18. (37) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 18. (38) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 19. (39) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 19. (40) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 20. (41) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 20. (42) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 21. (43) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 21.(44) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 22. (45) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 22. (46) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 23. (47) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 23. (48) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 24. (49) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 24. (50) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 25. (51) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 25. (52) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 26. (53) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 26. (54) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 27. (55) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 27. (56) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 28. (57) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 28.(58) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 29. (59) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 29. (60) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 30. (61) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 30. (62) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 31. (63) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 31. (64) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. (65) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 32. (66) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 33. (67) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 33. (68) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 34. (69) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 34. (70) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 35. (71) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 35.(72) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 36. (73) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 36. (74) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 37. (75) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 37. (76) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 38. (77) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 38. Polypeptide. (78) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 39. (79) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 39. (80) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 40. (81) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 40. (82) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 41. (83) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 41. (84) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 42. (85) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 42. (86) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 43. (87) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 43. (88) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 401. (89) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 401. (90) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 402. (91) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 402.(92) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 403. (93) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 403. (94) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 404. (95) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 404. (96) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 405. (97) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 405. (98) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 406. (99) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 406. (100) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 407. (101) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 407. (102) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 408. (103) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 408. (104) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 409. (105) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 409.(106) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 410. (107) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 410. (108) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 411. (109) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 411. (110) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 412. (111) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 412. (112) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 413. (113) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 413. (114) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 414. (115) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 414. (116) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 415. (117) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 415. (118) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 416. (119) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 416.(120) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 417. (121) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 417. (122) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 418. (123) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 418. (124) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 419. (125) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 419. (126) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 420. (127) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 420. (128) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 421. (129) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 421. (130) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 422. (131) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises SEQ ID NO: 422. (132) The chimeric polypeptide of any preceding embodiment, wherein the targeting polypeptide comprises Formula I. (133) The chimeric polypeptide of any preceding embodiment, wherein the chimeric polypeptide comprises a therapeutic agent. (134) The chimeric polypeptide of embodiment 133, wherein the therapeutic agent comprises a mammalian growth factor. (135) The chimeric polypeptide of embodiment 133 or embodiment 134, wherein the therapeutic agent comprises a bone morphogenetic protein (BMP).(136) The chimeric polypeptide of embodiment 135, wherein the BMP comprises BMP-2. (137) The chimeric polypeptide of embodiment 135, wherein the BMP2 comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. (138) The chimeric polypeptide of embodiment 135, wherein the BMP comprises SEQ ID NO: 32. (139) The chimeric polypeptide of embodiment 133 or embodiment 134, wherein the therapeutic agent comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a sequence set forth in Table B. (140) The chimeric polypeptide of embodiment 133 or embodiment 134, wherein the therapeutic agent comprises two or more therapeutic sequences, each therapeutic sequence comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a sequence set forth in Table B. (141) The chimeric polypeptide of embodiment 140, wherein the two or more therapeutic sequences are 2, 3, 4, or 5 therapeutic sequences. (142) The chimeric polypeptide of embodiment 140, wherein two or more is 2 to about 10. (143) The chimeric polypeptide of any preceding embodiment, comprising a linker. (144) The chimeric polypeptide of embodiment 143, wherein the linker comprises GSEG (SEQ ID NO: 702). (145) The chimeric polypeptide of embodiment 143 or embodiment 144, wherein the linker comprises SEGG (SEQ ID NO: 703). (146) The chimeric polypeptide of any one of embodiments 143-145, wherein the linker comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 701, or wherein the linker comprises SEQ ID NO: 701. (147) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 501, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 501. (148) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 502, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 502.(149) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 503, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 503. (150) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 504, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 504. (151) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 505. (152) The chimeric polypeptide of any preceding embodiment, wherein the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 506, or wherein the chimeric polypeptide comprises SEQ ID NO: 506. (153) The chimeric polypeptide of any preceding embodiment, wherein the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 507, or wherein the chimeric polypeptide comprises SEQ ID NO: 507. (154) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 508, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 508. (155) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 509, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 509. (156) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 510, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 510. (157) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 511, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 511. (158) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 512, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 512.(159) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 513, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 513. (160) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 514, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 514. (161) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 515, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 515. (162) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 516, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 516. (163) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 517, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 517. (164) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 518, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 518. (165) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 519, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 519. (166) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 520, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 520.(167) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 521, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 521. (168) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 522, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 522. (169) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 523, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 523. (170) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 524, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 524. (171) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 525, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 525. (172) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 526, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 526. (173) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 527, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 527. (174) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 528, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 528.(175) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 529, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 529. (176) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 530, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 530. (177) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 531, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 531. (178) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 532, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 532. (179) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 533, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 533. (180) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 534, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 534. (181) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 535, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 535. (182) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 536, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 536.(183) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 537, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 537. (184) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 538, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 538. (185) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 539, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 539. (186) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 540, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 540. (187) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 541, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 541. (188) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 542, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 542. (189) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 543, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 543. (190) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 544, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 544.(191) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 545, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 545. (192) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 546, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 546. (193) The chimeric polypeptide of any preceding embodiment, wherein the chimeric polypeptide comprises SEQ ID NO: 546. (193) The chimeric polypeptide of any preceding embodiment, wherein the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 547, wherein the sequence comprises X, or wherein the chimeric polypeptide comprises SEQ ID NO: 547. (194) The chimeric polypeptide of any preceding embodiment, wherein the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 548, wherein the sequence comprises X, or wherein the chimeric polypeptide comprises SEQ ID NO: 548. (195) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 549, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 549. (196) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 550, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 550. (197) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 551, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 551. (198) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 552, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 552. (199) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 553, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 553.(200) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 554, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 554. (201) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 555, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 555. (202) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 556, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 556. (203) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 557, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 557. (204) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 558, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 558. (205) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 559, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 559. (206) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 560, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 560. (207) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 561, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 561.(208) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 562, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 562. (209) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 563, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 563. (210) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 564, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 564. (211) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 565, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 565. (212) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 566, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 566. (213) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 567, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 567. (214) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 568, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 568. (215) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 569, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 569.(216) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 570, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 570. (217) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 571, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 571. (218) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 572, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 572. (219) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 573, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 573. (220) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 574, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 574. (221) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 575, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 575. (222) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 576, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 577. (223) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 578, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 579.(224) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 580, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 580. (225) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 581, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 581. (226) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 582, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 582. (227) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 583, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 583. (228) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 584, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 584. (229) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 585, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 585. (230) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 586, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 586. (231) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 587, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 587.(232) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 588, wherein the sequence comprises X; alternatively, the chimeric polypeptide comprises SEQ ID NO: 588. (233) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 589, wherein the sequence comprises X. Alternatively, the chimeric polypeptide comprises SEQ ID NO: 589. (234) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 590, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 590. (235) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 591, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 591. (236) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 592, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 592. (237) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 593, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 593. (238) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 594, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 594. (239) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 595, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 595. (240) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 596, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 596.(241) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 597, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 597. (242) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 598, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 598. (243) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 599, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 599. (244) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 600, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 600. (245) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 601, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 601. (246) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 602, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 602. (247) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 603, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 603. (248) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 604, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 604.(249) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 605, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 605. (250) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 606, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 606. (251) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 607, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 607. (252) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 608, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 608. (253) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 609, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 609. (254) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 610, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 610. (255) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 611, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 611. (256) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 612, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 612.(257) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 613, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 613. (258) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 614, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 614. (259) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 615, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 615. (260) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 616, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 616. (261) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 617, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 617. (262) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 618, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 618. (263) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 619, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 619. (264) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 620, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 620.(265) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 621, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 621. (266) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 622, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 622. (267) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 623, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 623. (268) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 624, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 624. (269) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 625, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 625. (270) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 626, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 626. (271) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 627, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 627. (272) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 628, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 628.(273) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 629, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 629. (274) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 630, wherein the sequence comprises X. Alternatively, the chimeric polypeptide comprises SEQ ID NO: 630. (275) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 631, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 631. (276) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 632, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 632. (277) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 633, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 633. (278) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 634, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 634. (279) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 635, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 635. (280) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 636, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 636. (281) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 637, wherein the sequence comprises X, or alternatively, the chimeric polypeptide comprises SEQ ID NO: 637.(282) The chimeric polypeptide of any preceding embodiment, comprising a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 638, wherein the sequence comprises X, or wherein the chimeric polypeptide comprises SEQ ID NO: 638. (283) A composition comprising the chimeric polypeptide of any preceding embodiment. (284) The composition of embodiment 283, further comprising a carrier material. (285) The composition of embodiment 284, wherein the targeting polypeptide is bound to a carrier material. (286) The composition of embodiment 284 or embodiment 285, wherein the carrier material comprises calcium phosphate. (287) The composition of embodiment 286, wherein the calcium phosphate comprises tricalcium phosphate. (288) The composition of embodiment 287, wherein the tricalcium phosphate comprises β-tricalcium phosphate. (289) The composition of any one of embodiments 284-288, wherein the carrier material comprises hydroxyapatite. (290) The composition of any one of embodiments 284-289, wherein the carrier material comprises alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicate, vanadate, and related ceramic minerals, or chelated divalent metal ions, or any combination thereof. (291) The composition of any one of embodiments 284-290, wherein the carrier material comprises fibers, powders, pastes, meshes, sponges, or scaffolds, or combinations thereof. (292) A method of treating a subject in need thereof, the method comprising delivering to the subject the chimeric polypeptide of any one of embodiments 1-282. (293) A method of treating a subject in need thereof, the method comprising delivering to the subject the composition of any one of embodiments 283-291. (294) The method of embodiment 292 or embodiment 293, wherein the chimeric polypeptide is used to treat a bone defect in a subject. (295) The method of embodiment 292 or embodiment 293, wherein the chimeric polypeptide is used to treat a cartilage defect in a subject. (296) The method of embodiment 292 or embodiment 293, wherein the chimeric polypeptide is used to treat a soft tissue defect in a subject. (297) The method of embodiment 292 or embodiment 293, wherein the chimeric polypeptide is used to treat a tendon defect in a subject.(298) The method of embodiment 292 or embodiment 293, wherein the chimeric polypeptide is used to treat a fascial defect in a subject. (299) The method of embodiment 292 or embodiment 293, wherein the chimeric polypeptide is used to treat a ligament defect in a subject. (300) The method of embodiment 292 or embodiment 293, wherein the chimeric polypeptide is used to treat an organ defect in a subject. (301) The method of embodiment 292 or embodiment 293, wherein the chimeric polypeptide is used to treat a bone-tendon tissue defect in a subject. (302) The method of embodiment 292 or embodiment 293, wherein the chimeric polypeptide is used to treat a skin defect in a subject. (303) The method of embodiment 292 or embodiment 293, wherein the chimeric polypeptide is used to treat an osteochondral defect in a subject. (304) The method of embodiment 292 or embodiment 293, wherein the method is performed for spinal fusion of a subject. (305) The method of embodiment 304, wherein the spinal fusion comprises posterior lumbar fusion (PLF). (306) The method of embodiment 304, wherein the spinal fusion comprises interbody fusion. (307) The method of embodiment 292 or embodiment 293, wherein the method is performed for bone trauma repair. (308) The method of embodiment 292 or embodiment 293, wherein the method is performed for dental repair. (309) The method of embodiment 292 or embodiment 293, wherein the method is performed for craniomaxillofacial repair. (310) The method of embodiment 292 or embodiment 293, wherein the method is performed for ankle fusion. (311) The method of embodiment 292 or embodiment 293, wherein the method is performed for vertebroplasty. (312) The method of embodiment 292 or embodiment 293, wherein the method is performed for balloon osteoplasty. (313) The method of embodiment 292 or embodiment 293, wherein the method is performed for craniomaxillary scaphoid fracture. (314) The method of embodiment 292 or embodiment 293, wherein the method is performed for tendon-osseous repair. (315) The method of embodiment 292 or embodiment 293, wherein the method is performed for treating osteoporosis. (316) The method of embodiment 292 or embodiment 293, wherein the method is performed for treating avascular necrosis.(317) The method of embodiment 292 or embodiment 293, wherein the method is performed to treat a congenital skeletal malformation. (318) The method of embodiment 292 or embodiment 293, wherein the method is performed for rib reconstruction. (319) The method of embodiment 292 or embodiment 293, wherein the method is performed for subchondral bone repair. (320) The method of embodiment 292 or embodiment 293, wherein the method is performed for cartilage repair. (321) The method of embodiment 292 or embodiment 293, wherein the method is performed on hair follicles (BMP-2 is involved in hair follicle development). (322) The method of any one of embodiments 292-321, wherein the subject is a mammal. (323) The method of any one of embodiments 292-321, wherein the subject is a human. (324) The method of any one of embodiments 292-321, wherein the subject is a mammal other than a human. (325) The method of embodiment 324, wherein the method is used in veterinary applications. (326) The method of any one of embodiments 292-325, wherein delivery comprises surgical implantation into the subject.

[0280] To determine the KD value of any of the chimeric polypeptides described herein for targeting a carrier material, such as β-TCP, various different methods known in the art can be used. Non-limiting examples include electrophoretic mobility shift assays, filter binding assays, surface plasmon resonance, and biomolecular binding kinetic assays.

[0281] In some embodiments, the chimeric polypeptides provided herein are useful orthopedic materials and can be used as bone void fillers and for bone reconstruction. In some embodiments, the chimeric polypeptides described herein are osteoconductive and readily resorbable.

[0282] Linker In some instances, the adjacent pair of two targeting polypeptides are directly adjacent to each other. In some instances, the adjacent pair of two targeting polypeptides are separated by a linker sequence.

[0283] In some embodiments of the chimeric polypeptides provided herein comprising a targeting polypeptide and a therapeutic agent, the targeting polypeptide and the therapeutic agent are separated by a linker sequence. In some embodiments, a linker sequence is present between the two targeting polypeptides and / or between the targeting polypeptide and the therapeutic agent. In some examples, the therapeutic agent comprises a mammalian growth factor. For example, BMP-2 comprises SEQ ID NO: 32. In some examples, the targeting polypeptide comprises one or more sequences in Table B. In some embodiments of the chimeric polypeptides comprising a linker disposed between the targeting polypeptide and the therapeutic agent, the presence of the linker increases the solubility of the chimeric polypeptide compared to a chimeric polypeptide that does not comprise a linker. In some embodiments, the linker is optimized for sequence and / or length. In some embodiments, the chimeric polypeptide comprising a linker is more soluble compared to a chimeric polypeptide that does not comprise a linker. In some embodiments, the therapeutic agent in a chimeric polypeptide comprising a linker is more bioavailable than without the linker.

[0284] In some embodiments, the sequence comprises a sequence of about 5 to about 50 amino acids. In some embodiments, the linker is a flexible linker, and at least about 5 of the amino acids do not have a regular secondary structure. In some embodiments, the regular secondary structure comprises any helical structure, such as an alpha helix, a 3' helix, a π helix, a beta turn, an omega loop, and / or a beta sheet. In some embodiments, the linker comprises at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% glycine, alanine, and serine, glycine, alanine, glycine, serine, alanine, or glycine, alanine, and serine. In some embodiments, the linker comprises at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% combinations of alanine, serine, glycine, and threonine. In some embodiments, the linker comprises one, two, three, four, or five sequences having GSEG (SEQ ID NO: 702). In some embodiments, the linker comprises one, two, three, four, or five sequences having SEGG (SEQ ID NO: 703). In some embodiments, linkers comprising a majority of A, S, G, and T improve the solubility of the chimeric polypeptide. In some embodiments, linkers comprising a length of about 30 to about 45 amino acids improve the solubility of the chimeric polypeptide.

[0285] In some embodiments, the linker comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to ASGAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTG (SEQ ID NO: 701). In some embodiments, the linker comprises at least about 10, 15, 20, 25, or 30 contiguous amino acids of SEQ ID NO: 701. In some embodiments, the linker comprises a sequence at least about 90% identical to SEQ ID NO: 701. In some embodiments, the linker comprises SEQ ID NO: 701. In some embodiments, the linker sequence is positioned between the targeting polypeptide and the therapeutic agent. In some examples, the therapeutic agent comprises a mammalian growth factor. For example, BMP-2 comprises SEQ ID NO: 32. In some examples, the targeting polypeptide comprises one or more sequences of Table A.

[0286] In some embodiments, the linker sequence comprises or consists of TGGSGEGGTGASTGGSAGTGGSGGTTSGEAGGSSGAG (SEQ ID NO: 33) or GSGATG (SEQ ID NO: 45). In some examples, the chimeric polypeptide comprises a linker having an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) sequence identity to SEQ ID NO: 33.

[0287] In some embodiments, the linker sequence comprises GSGS (SEQ ID NO: 705), GSGSGS (SEQ ID NO: 706), SGSG (SEQ ID NO: 707), SGSGSG (SEQ ID NO: 708), GSSG (SEQ ID NO: 709), SS, or GGGGS (SEQ ID NO: 710), or a combination thereof.

[0288] In some embodiments, the linker sequence may be from 1 to about 100 amino acids, from 1 to about 95 amino acids, from 1 to about 90 amino acids, from 1 to about 85 amino acids, from 1 to about 80 amino acids, from 1 to about 75 amino acids, from 1 to about 70 amino acids, from 1 to about 65 amino acids, from 1 to about 60 amino acids, from 1 to about 55 amino acids, from 1 to about 50 amino acids, from 1 to about 45 amino acids, from 1 to about 40 amino acids, from 1 to about 35 amino acids, from 1 to about 30 amino acids, from 1 to about 25 amino acids, or from 1 to about 35 amino acids. amino acids to about 20 amino acids, 1 amino acid to about 15 amino acids, 1 amino acid to about 10 amino acids, 1 amino acid to about 5 amino acids, about 5 amino acids to about 100 amino acids, about 5 amino acids to about 95 amino acids, about 5 amino acids to about 90 amino acids, about 5 amino acids to about 85 amino acids, about 5 amino acids to about 80 amino acids, about 5 amino acids to about 75 amino acids, about 5 amino acids to about 70 amino acids, about 5 amino acids to about 65 amino acids, about 5 amino acids to about 60 amino acids, about 5 amino acids to about 55 amino acids, about 5 amino acids to about 50 amino acids, about 5 amino acids to about 45 amino acids, about 5 amino acids to about 40 amino acids amino acids, about 5 to about 35 amino acids, about 5 to about 30 amino acids, about 5 to about 25 amino acids, about 5 to about 20 amino acids, about 5 to about 15 amino acids, about 5 to about 10 amino acids, about 10 to about 100 amino acids, about 10 to about 95 amino acids, about 10 to about 90 amino acids, about 10 to about 85 amino acids, about 10 to about 80 amino acids, about 10 to about 75 amino acids, about 10 to about 70 amino acids, about 10 to about 65 amino acids, about 10 to about 60 amino acids, about 10 to about 5 5 amino acids, about 10 to about 50 amino acids, about 10 to about 45 amino acids, about 10 to about 40 amino acids, about 10 to about 35 amino acids, about 10 to about 30 amino acids, about 10 to about 25 amino acids, about 10 to about 20 amino acids, about 10 to about 15 amino acids, about 20 to about 100 amino acids, about 20 to about 95 amino acids, about 20 to about 90 amino acids, about 20 to about 85 amino acids, about 20 to about 80 amino acids, about 20 to about 75 amino acids, about 20 to about 70 amino acids,It may be about 20 to about 65 amino acids, about 20 to about 60 amino acids, about 20 to about 55 amino acids, about 20 to about 50 amino acids, about 20 to about 45 amino acids, about 20 to about 40 amino acids, about 20 to about 35 amino acids, about 20 to about 30 amino acids, about 20 to about 25 amino acids, about 30 to about 100 amino acids, about 30 to about 95 amino acids, about 30 to about 90 amino acids, about 30 to about 85 amino acids, about 30 to about 80 amino acids, about 30 to about 75 amino acids, about 30 to about 70 amino acids, about 30 to about 65 amino acids, about 30 to about 60 amino acids, about 30 to about 55 amino acids, about 30 to about 50 amino acids, about 30 to about 45 amino acids, about 30 to about 40 amino acids, or about 30 to about 35 amino acids.

[0289] growth factors The targeting polypeptides described herein can be tethered to a mammalian growth factor. In some embodiments, a linker sequence (e.g., any of the linker sequences described herein or known in the art) is placed between the targeting polypeptide and the mammalian growth factor.

[0290] Mammalian growth factors can be osteoinductive molecules that can initiate or enhance the bone repair process. Bone morphogenetic proteins (BMPs) represent a distinct subset of the transforming growth factor-β (TGFbeta) family. Many of these BMPs (BMP-2, BMP-7, and BMP-14) improve the rate of bone healing in defects and nonunions.

[0291] Non-limiting examples of mammalian growth factors are described herein. In some examples, the mammalian growth factor is epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-1), fibroblast growth factor (FGF), fibroblast growth factor 2 (FGF2), fibroblast growth factor 18 (FGF18), transforming growth factor alpha (TGF-α), transforming growth factor beta (TGF-β), transforming growth factor beta-1 (TGF-β1), transforming growth factor beta 3 (TGF-β3), osteogenic protein 1 (OP-1), osteogenic protein 1 (OP-2), osteogenic protein 3 (OP-3), Bone morphogenetic protein 2 (BMP-2), bone morphogenetic protein 3 (BMP-3), bone morphogenetic protein 4 (BMP-4), bone morphogenetic protein 5 (BMP-5), bone morphogenetic protein 6 (BMP-6), bone morphogenetic protein 7 (BMP-7), bone morphogenetic protein 9 (BMP-9), bone morphogenetic protein 10 (BMP-10), bone morphogenetic protein 11 (BMP-11), bone morphogenetic protein 12 (BMP-12), bone morphogenetic protein 13 (BMP-13), bone morphogenetic protein 15 (BMP-15), dentin phosphoprotein (DPP), plant-related growth factor (Vgr), growth differentiation factor 1 (GDF-1), growth differentiation factor 3 (GDF-3), growth differentiation factor 5 (GDF-5), growth differentiation factor 6 (GDF-6), growth differentiation factor 7 (GDF-7), growth differentiation factor 8 (GDF8), growth differentiation factor 11 (GDF11), growth differentiation factor 15 (GDF15), vascular endothelial growth factor (VEGF), hyaluronic acid-binding protein (HABP), and collagen-binding protein (CBP), fibroblast growth factor 18 (FGF-18), keratinocyte growth factor (KGF), tumor necrosis f...

Claims

1. 1. A polypeptide composition comprising: a targeting polypeptide comprising a sequence at least 80% identical to SEQ ID NO:22 (LLADTTHHRPWT VIGESTHHRPWS IIGESSHHKPFT GLGDTTHHRPWG ILAESTHHKPWT); and a therapeutic polypeptide comprising a sequence at least 80% identical to a sequence selected from SEQ ID NOs:32, 46-71, 73-77, 79-101, 152, 168, 176, 268.

2. The polypeptide composition of claim 1, wherein the therapeutic polypeptide comprises a sequence at least 90% identical to a sequence selected from SEQ ID NOs: 32, 46-71, 73-77, 79-101, 152, 168, 176, and 268.

3. The polypeptide composition of claim 1, wherein the therapeutic polypeptide comprises a sequence selected from SEQ ID NOs: 32, 46-71, 73-77, 79-101, 152, 168, 176, and 268.

4. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 80%, 85%, 90%, or 95% identical to SEQ ID NO:

32.

5. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises SEQ ID NO:

32.

6. The polypeptide composition of claim 1 , wherein the targeting polypeptide comprises a sequence at least 90% or 95% identical to SEQ ID NO:

22.

7. The polypeptide composition of claim 1 , wherein the targeting polypeptide comprises SEQ ID NO:

22.

8. The polypeptide composition of claim 2 , wherein the targeting polypeptide comprises a sequence at least 90% or 95% identical to SEQ ID NO:

22.

9. The polypeptide composition of claim 2 , wherein the targeting polypeptide comprises SEQ ID NO:

22.

10. The polypeptide composition of claim 3 , wherein the targeting polypeptide comprises a sequence at least 90% or 95% identical to SEQ ID NO:

22.

11. The polypeptide composition of claim 3 , wherein the targeting polypeptide comprises SEQ ID NO:

22.

12. The polypeptide composition of claim 4, wherein the targeting polypeptide comprises a sequence at least 90% or 95% identical to SEQ ID NO:

22.

13. The polypeptide composition of claim 4, wherein the targeting polypeptide comprises SEQ ID NO:

22.

14. The polypeptide composition of claim 5 , wherein the targeting polypeptide comprises a sequence at least 90% or 95% identical to SEQ ID NO:

22.

15. The polypeptide composition of claim 5 , wherein the targeting polypeptide comprises SEQ ID NO:

22.

16. 1. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:551 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), wherein said polypeptide composition comprises X, wherein X comprises SEQ ID NO:22 (LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWT).

17. 17. The polypeptide composition of claim 16, comprising a sequence at least about 90% or 95% identical to SEQ ID NO:

551.

18. 1. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:639 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), wherein said polypeptide composition comprises X, wherein X comprises SEQ ID NO:2 (VIGESTHHRPWS).

19. 19. The polypeptide composition of claim 18, comprising a sequence at least about 90% or 95% identical to SEQ ID NO:

639.

20. 1. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:519 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), The polypeptide composition comprises X, wherein X comprises SEQ ID NO: 6 (IIGESSHHKPFT).

21. 21. The polypeptide composition of claim 20, comprising a sequence at least about 90% or 95% identical to SEQ ID NO:

519.

22. 1. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:521 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), The polypeptide composition comprises X, wherein X comprises SEQ ID NO: 7 (GLGDTTHHRPWG).

23. 23. The polypeptide composition of claim 22, comprising a sequence at least about 90% or 95% identical to SEQ ID NO:

521.

24. 1. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:515 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), wherein said polypeptide composition comprises X, wherein X comprises SEQ ID NO:4 (ILAESTHHKPWT).

25. 25. The polypeptide composition of claim 24, comprising a sequence at least about 90% or 95% identical to SEQ ID NO:

515.

26. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:

501.

27. 27. The polypeptide composition of claim 26, wherein the sequence is at least about 90% or 95% identical to SEQ ID NO:

501.

28. 27. The polypeptide composition of claim 26, wherein the sequence comprises SEQ ID NO:

501.

29. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:

507.

30. 30. The polypeptide composition of claim 29, wherein the sequence is at least about 90% or 95% identical to SEQ ID NO:

507.

31. 30. The polypeptide composition of claim 29, wherein the sequence comprises SEQ ID NO:

507.

32. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:

506.

33. 33. The polypeptide composition of claim 32, wherein the sequence is at least about 90% or 95% identical to SEQ ID NO:

506.

34. 33. The polypeptide composition of claim 32, wherein the sequence comprises SEQ ID NO:

506.

35. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:

505.

36. 36. The polypeptide composition of claim 35, wherein the sequence is at least about 90% or 95% identical to SEQ ID NO:

505.

37. 36. The polypeptide composition of claim 35, wherein the sequence comprises SEQ ID NO:

505.

38. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:

504.

39. 39. The polypeptide composition of claim 38, wherein the sequence is at least about 90% or 95% identical to SEQ ID NO:

504.

40. 39. The polypeptide composition of claim 38, wherein the sequence comprises SEQ ID NO:

504.

41. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:

503.

42. 42. The polypeptide composition of claim 41, wherein the sequence is at least about 90% or 95% identical to SEQ ID NO:

503.

43. 42. The polypeptide composition of claim 41, wherein the sequence comprises SEQ ID NO:

503.

44. A polypeptide composition comprising a sequence at least about 80% identical to SEQ ID NO:

502.

45. 45. The polypeptide composition of claim 44, wherein the sequence is at least about 90% or 95% identical to SEQ ID NO:

502.

46. 45. The polypeptide composition of claim 44, wherein the sequence comprises SEQ ID NO:

502.

47. A polypeptide composition comprising a targeting polypeptide comprising a sequence at least 80% identical to SEQ ID NO: 22 (LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWT) and a therapeutic polypeptide comprising a bone morphogenetic protein (BMP).

48. 48. The polypeptide composition of claim 47, wherein the BMP is BMP-2.

49. A nucleic acid encoding a polypeptide composition according to any one of claims 1-48.

50. 50. A vector comprising the nucleic acid of claim 49.

51. A device comprising the polypeptide composition of any one of claims 1-48 and a carrier material.

52. 52. The device of claim 51, wherein the polypeptide composition is bound to a carrier material.

53. 53. The device of claim 51 or 52, wherein the carrier material comprises calcium phosphate.

54. 53. The device of claim 51 or 52, wherein the carrier material comprises hydroxyapatite.

55. 53. The device of claim 51 or 52, wherein the carrier material comprises alpha tricalcium phosphate, fluoroapatite, bone (e.g., demineralized bone), glass (bioglass), such as silicates, vanadates, and related ceramic minerals, or chelated divalent metal ions, or any combination thereof.

56. 10. A method of treating a subject in need thereof, said method comprising the step of delivering to said subject a polypeptide composition according to any one of claims 1-48 or a device according to any one of claims 51-55.

57. 57. The method of claim 56, wherein the polypeptide composition or device is delivered to treat a bone defect in a subject.

58. 58. The method of claim 57, wherein at least about 0.5 mg of the polypeptide composition per cc of defect volume is delivered to the subject.

59. 59. The method of claim 57 or 58, wherein about 0.5 mg to about 10 mg of the polypeptide composition per cc of defect volume is delivered to the subject.

60. 1. A method of delivering a therapeutic agent to an organ or tissue of a subject, the method comprising the steps of delivering to the organ or tissue a carrier material and a therapeutic agent, wherein the therapeutic agent is bound to the carrier material via a targeting polypeptide, the targeting polypeptide comprising: (a) a sequence at least 80% identical to SEQ ID NO: 22; (b) a sequence at least 80% identical to SEQ ID NO: 402; (c) a sequence at least 80% identical to SEQ ID NO: 401; (d) a sequence at least 80% identical to SEQ ID NO:413 ((X1)(X2)), wherein X1 comprises SEQ ID NO:1 and X2 comprises SEQ ID NO:2 and SEQ ID NO:6; (e) a sequence at least 80% identical to SEQ ID NO: 21; (f) a sequence at least 80% identical to SEQ ID NO:414 ((X1)(X2)), wherein X1 comprises SEQ ID NO:2 and X2 comprises SEQ ID NO:6 and SEQ ID NO:7; (g) a sequence at least 80% identical to SEQ ID NO:416 ((X1)(X2)), wherein X1 comprises SEQ ID NO:6 and X2 comprises SEQ ID NO:7 and SEQ ID NO:4; (h) a sequence at least 80% identical to SEQ ID NO: 408 ((X1)(X2)), wherein X1 comprises SEQ ID NO: 1 and X2 comprises SEQ ID NO: 2; (i) a sequence at least 80% identical to SEQ ID NO: 20; (j) a sequence at least 80% identical to SEQ ID NO: 409 ((X1)(X2)), wherein X1 comprises SEQ ID NO: 2 and X2 comprises SEQ ID NO: 6; (k) a sequence at least 80% identical to SEQ ID NO: 411 ((X1)(X2)), wherein X1 comprises SEQ ID NO: 6 and X2 comprises SEQ ID NO: 7; (l) a sequence at least 80% identical to SEQ ID NO: 412 ((X1)(X2)), wherein X1 comprises SEQ ID NO: 7 and X2 comprises SEQ ID NO: 4; (m) a sequence at least 80% identical to SEQ ID NO: 2 (VIGESTHHRPWS); (n) a sequence at least 80% identical to SEQ ID NO: 4 (ILAESTHHKPWT); (o) a sequence at least 80% identical to SEQ ID NO: 6 (IIGESSHHKPFT); (p) a sequence at least 80% identical to SEQ ID NO: 7 (GLGDTTHHRPWG), or (q) A method comprising any combination of two or more of (a) through (p).

61. 61. The method of claim 60, wherein the carrier material comprises calcium phosphate.

62. 62. The method of claim 60 or 61, wherein the targeting polypeptide is linked to a therapeutic agent.

63. The method of any one of claims 60-62, wherein the therapeutic agent comprises a growth factor.

64. The method of any one of claims 60-63, wherein the therapeutic agent comprises a BMP.

65. 65. The method of claim 64, wherein the BMP comprises BMP-2.

66. 64. The method of any one of claims 60-63, wherein the therapeutic agent comprises a sequence that is at least about 80% identical to SEQ ID NO:

32.

67. 64. The method of any one of claims 60-63, wherein the therapeutic agent comprises a sequence that is at least about 80% identical to any one of SEQ ID NOs: 46-71, 73-77, 79-101, 152, 168, 176, 268.

68. 68. The method of any one of claims 60-67, wherein the therapeutic agent is delivered to treat a bone defect in a subject.

69. 69. The method of claim 68, wherein at least about 0.5 mg of therapeutic agent is delivered per cc of defect volume.

70. 70. The method of claim 68 or 69, wherein about 0.5 mg to about 10 mg of therapeutic agent is delivered per cc of defect volume.

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