Bone formation compositions and methods of use

Abstract

The present disclosure provides compositions and methods treating spinal conditions using interbody lumbar fusion. The compositions comprise β-TCP as a ceramic scaffold and a chimeric recombinant BMP -2 (tBMP-2), which has a portion of BMP-2 fused to several β-TCP binding peptides. The β-TCP and tBMP-2 are associated non-covalently. The method may be used with interbody cages, wherein the interbody cage comprises titanium, polyetheretherketone (PEEK), polyetherketoneketone (PEKK), carbon fiber, grafted or synthetic bone, or any combination thereof. The surgical procedures can be selected from Transforaminal Lumbar Interbody Fusion (TLIF), Lateral Lumbar Interbody Fusion (LLIF), Posterior Lumbar Interbody Fusion (PLIF), Anterior Lumbar Interbody Fusion (ALIF), Oblique Lateral Interbody Fusion (OLIF), and Extreme Lateral Interbody Fusion (XLIF), Interspinous Process Fusion (ILIF), Anterior Cervical Discectomy and Fusion (ACDF), Posterior Spinal Fusion (PSF), Posterolateral Spinal Fusion (PLF) facet fusion, interspinous fusion, Sacroiliac Joint Fusion, or Kyphoplasty.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application Serial No. 63 / 549,401, filed February 2, 2024, which is incorporated by reference herein in its entirety. SEQUENCE LISTING This application contains a Sequence Listing, which is submitted herewith in XML format, and is hereby incorporated by reference in its entirety. The XML copy, created on January 31, 2025, is named 50222-714_601.xml and is 629,840 bytes in size. STATEMENT AS TO FEDERALLY SPONSORED RESEARCH This invention was made with government support under Contract number W81XWH-20-1-0305 and W81XWH-22-1-0875 awarded by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense. The government has certain rights in the invention. BACKGROUND Degenerative spinal conditions have a tremendous global impact on lost productivity and diminished quality of life. When a spinal fusion surgical procedure is performed to reduce pain and motion at the affected spinal segment, bone graft material is implanted in the disc space or along the posterior aspects of the spine to assist the fusion process. The gold standard of grafting material is autograft from the iliac crest, despite the risk for pain and other adverse events associated with the harvest procedure. SUMMARY Autograft replacement commonly incorporates an osteoinductive growth factor, bone morphogenetic protein 2 (BMP-2). However, use of BMP-2 in spinal fusion procedures can lead to adverse events such as inflammation and postoperative radiculitis, bone resorption and heterotopic bone formation. In some aspects, provided herein are variants of BMP-2 that bind specifically to a ceramic component of a scaffold. The BMP-2 and scaffold combination device provides a distinct advantage in that it may limit off target effects such as heterotopic bone growth and provide more precise localization of new bone formation within the desired area, thus enabling medical practitioners to use a lower dose of BMP-2 and / or achieve a desired effect for a sustained duration. Non-limiting example scaffolds include ceramic components such as calcium phosphate, and specifically, beta-tricalcium phosphate (bTCP). A non-limiting method of use includes interbody fusion, where the BMP-2 and scaffold are optionally administered with an interbody cage. Provided herein is an example method of treating the spine in a subject in need thereof, the method comprising implanting a device in a cavity of the subject in a spinal procedure, wherein the device comprises a recombinant BMP-2 comprising a binding peptide, and a ceramic scaffold; and wherein the spinal procedure is a lumbar interbody fusion procedure selected from Transforaminal Lumbar Interbody Fusion (TLIF), Lateral Lumbar Interbody Fusion (LLIF), Posterior Lumbar Interbody Fusion (PLIF), Anterior Lumbar Interbody Fusion (ALIF), Oblique Lateral Interbody Fusion (OLIF), and Extreme Lateral Interbody Fusion (XLIF). In some embodiments, the subject has a degenerative disc disease, iatrogenic injury to the spine, congenital spinal condition or deformity, scoliosis, spondylolisthesis, spinal stenosis, fractured vertebra, trauma to the spine, infection of the spine, or tumor of the spine. Also provided herein is an example method for treating the spine in a subject in need thereof, the method comprising implanting a device in a cavity of the subject in a spinal procedure, wherein the device comprises a recombinant BMP-2 comprising a binding peptide, and a ceramic scaffold; and wherein the spinal procedure is Interspinous Process Fusion (ILIF), Anterior Cervical Discectomy and Fusion (ACDF), Posterior Spinal Fusion (PSF), Posterolateral Spinal Fusion (PLF) facet fusion, interspinous fusion, Sacroiliac Joint Fusion, or Kyphoplasty. In some embodiments, the subject has a degenerative disc disease, iatrogenic injury to the spine, congenital spinal condition or deformity, scoliosis, spondylolisthesis, spinal stenosis, fractured vertebra, trauma to the spine, infection of the spine, or tumor of the spine. Also provided herein is a method for treating a condition of the spine in a subject in need thereof, the method comprising implanting a device in a cavity of the subject during a spinal procedure, wherein the device comprises a ceramic scaffold and a recombinant BMP-2 comprising a binding peptide; wherein the condition of the spine is degenerative disc disease, iatrogenic injury to the spine, congenital spinal condition or deformity, scoliosis, spondylolisthesis, spinal stenosis, fractured vertebra, trauma to the spine, infection of the spine, or tumor of the spine. In any of the methods herein, in some embodiments, the recombinant BMP-2 is non-covalently bonded to the ceramic scaffold. In any of the methods herein, in some embodiments, the treating results in improved spinal stability, reduced back pain, increased mobility, or reduced deformation of the spine, or a combination of two or more thereof. In any of the methods herein, in some embodiments, about 0.08 mg to about 8 mg BMP-2 / cc of the cavity is implanted in the subject, and / or wherein about 0.08 mg to about 8 mg BMP- 2 / cc of the ceramic scaffold is implanted in the subject. In any of the methods herein, in some embodiments, about 0.4 mg to about 4 mg BMP-2 / cc of the cavity is implanted in the subject, and / or wherein about 0.4 mg to about 4 mg BMP-2 / cc of the ceramic scaffold is implanted in the subject. In any of the methods herein, in some embodiments, about 0.8 mg to about 2 mg BMP-2 / cc of the cavity is implanted in the subject, and / or wherein about 0.8 mg to about 2 mg BMP-2 / cc of the ceramic scaffold is implanted in the subject. In any of the methods herein, in some embodiments, about 0.8 mg BMP-2 / cc of the cavity is implanted in the subject, and / or wherein about 0.8 mg BMP-2 / cc of the ceramic scaffold is implanted in the subject. In any of the methods herein, in some embodiments, about 2 mg BMP-2 / cc of the cavity is implanted in the subject, and / or wherein about 2 mg BMP-2 / cc of the ceramic scaffold is implanted in the subject. In any of the methods herein, in some embodiments, the ceramic scaffold comprises tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, or a combination thereof. In any of the methods herein, in some embodiments, the binding peptide comprises one or more peptides of Table 1 or Table 2. In any of the methods herein, in some embodiments, the recombinant BMP-2 comprises SEQ ID NO: 434 or 435, or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 434 or 435. In any of the methods herein, in some embodiments, the subject does not require a secondary surgical intervention within 24 months of the implanting. In any of the methods herein, in some embodiments, after implanting, the neurological status of the subject is maintained or improved. In any of the methods herein, in some embodiments, the subject’s Oswestry Disability Index is decreased after the implanting. In any of the methods herein, in some embodiments, the subject’s pain is reduced after the implanting, wherein the pain is optionally reduced within 24 months after implanting as compared to before the implanting. In any of the methods herein, in some embodiments, the subject has bone fusion as assessed by radiographic fusion assessment, optionally as assessed by CT (computed tomography). In some embodiments, the device further comprises an interbody cage, anterior cage, posterior cage, expandable cage, corpectomy cage, biodegradable cage, artificial disc, or a grafted cage. In some embodiments, the interbody cage comprises titanium, polyetheretherketone (PEEK), polyetherketoneketone (PEKK), carbon fiber, grafted or synthetic bone, or any combination thereof. In some embodiments, the subject has the presence of bridging bone, optionally as assessed by CT (computed tomography). In some embodiments, the spinal procedure is a non-interbody procedure. The details of one or more embodiments of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the disclosure will be apparent from the description and drawings, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A is an example composition comprising a calcium phosphate scaffold coated with a BMP-2 FIG. IB is an example surgical approach showing the placement of a composition (e.g., of FIG. 1A) with an interbody cage into a subject. FIG. 2 demonstrates implantation of an interbody cage with a composition (e.g., of FIG. 1 A) for single level lumbar interbody fusion of sheep. FIG. 3 shows CT scans demonstrating lumbar fusion of sheep over a period of 26 weeks following implantation of lumbar interbody devices containing either iliac crest bone grafts (ICBG), low dose (0.8 mg / cc) tBMP-2 bone grafts, or high dose (2.0 mg / cc) tBMP-2 bone grafts. FIG. 4 shows the average fusion scores based on the CT scans and FIG. 5 shows the mean bone development within the available lumbar void. FIG. 6 shows 26-week histology obtained in the ICBG, low tBMP-2, and high tBMP-2 groups, demonstrating the bridging of bone. FIG. 7A shows 26-week histology demonstrating marrow formation, bone formation, and osteoblast and graft fibers within ICBG treated sheep, while FIG. 7B shows 26-week histology demonstrating marrow formation, bone formation, and osteoblast and graft fibers within tBMP-2 treated sheep. FIG. 8 are microCT and H&E histology images from all treatment groups of the rabbit posterolateral fusion study described in Example 7: from the top, left, going clockwise: Group 1, Group 2, Group 4, and Group 3. FIG. 9A is an image representing the surgical approach and placement (FIG. 9B) of a device within a PEEK interbody device. DETAILED DESCRIPTION Various compositions, such as growth factors, scaffolds, and devices comprising the growth factors and scaffolds are provided herein. The device may comprise a scaffold coated with a growth factor, e.g., a tetherable growth factor for a desired therapeutic effect, such as promotion of bone growth after implantation of the device. The compositions may be used for the treatment of degenerative diseases of the lumbosacral spine. In particular, the compositions may be used for, for example, but not limited to, an interbody fusion. Methods of Treatment In one aspect, provided is a method of administering to a subject a composition herein, e.g., a bone morphogenetic protein-2 (BMP-2) and / or scaffold. In some methods, the subject is treated with a device composition comprising the BMP-2 and the scaffold. In some instances, the subject treated with the composition is in need of a bone graft, optionally with an interbody cage. In some instances, the composition is effective for spinal fusion. In some embodiments, provided herein is a method of promoting spinal health, reducing spinal pain, or increasing spinal stability in a subject in need thereof, or any combination thereof, the method comprising administering to the subject a composition comprising a BMP-2 and a scaffold, wherein the BMP-2 is non-covalently bonded to the scaffold. In some embodiments, the BMP-2 / scaffold combined device is implanted between two or more vertebrae, or between one or more vertebra and the sacrum, i.e., in a spinal fusion procedure. In some embodiments, the BMP-2 / scaffold surrounds or is placed adjacent or lateral (e.g., anterior, posterior) to one or more vertebrae. In some embodiments, the BMP-2 / scaffold is placed anteriorly, and external to an interbody cage, in order to fill the disc space between two vertebrae. In some embodiments, method comprises implanting a BMP-2 / scaffold device adjacent to a spinal fusion surgery site. In some embodiments, the method comprises implanting a BMP-2 / scaffold device in a non-interbody spinal fusion surgery site. In some embodiments, the non-interbody spinal fusion is a noninterbody lumbar spine fusion, including but not limited to posterior spinal fusion (PSF) and / or posterolateral spinal fusion (PLF). In some embodiments, the non-interbody spinal fusion is a facet fusion, interspinous fusion, or a sacroiliac joint fusion. In some embodiments, method comprises administering a BMP-2 / scaffold device optionally housed within an interbody cage. In some embodiments, the BMP-2 / scaffold device is affixed to an interbody cage. In some embodiments, the method comprises placing a BMP-2 / scaffold device in the form of an amorphous and / or filamentous device within the space between vertebrae or between a vertebra and the sacrum. In some embodiments, (e.g., in patients surgically treated via an ALIF (anterior lumbar interbody fusion) surgery), the method comprises implanting a BMP-2 / scaffold device in the subject, within an intervertebral space, optionally within an implanted interbody cage. In some embodiments, the method further comprises filling the disc space around the interbody cage with autologous bone graft or allograft (such as commercially available allograft products comprising only demineralized bone matrix and / or mineralized allograft chips, without any other components). In some embodiments, the BMP-2 scaffold may be admixed with the autologous, allograft or other commercial bone grafts in any ratio for placement in any of such locations. In some embodiments, the method further comprises filling the disc space around the optional interbody cage with a BMP-2 / scaffold composition. In some embodiments, the method comprises implanting a BMP-2 / scaffold device in the subject, within an intervertebral space, within an implanted interbody cage, and also filling the space around the interbody cage. In some embodiments, the method comprises implanting a BMP-2 / scaffold device in the subject, only within an interbody fusion cage, to support bone healing inside the intervertebral space. In some embodiments, e.g., wherein the subject is undergoing surgery for ALIF or LLIF, the BMP-2 / scaffold composition herein is primarily or exclusively placed within an interbody cage. In some embodiments, the method comprises performing an ALIF procedure using an anterior approach by making an incision in the abdomen. In some embodiments, the method comprises performing an LLIF procedure by making one or more incisions on the patient’s side. In some embodiments, the method comprises accessing the disc space anteriorly, laterally or anteriolaterally and removing disc material (including the cartilaginous endplates) to access bleeding bone. In some embodiments, the method optionally comprises inserting an interbody cage into the disc space. In some embodiments, the method further comprises inserting posterior rod and screw instrumentation for stabilization, e.g., through an additional posterior access. In some embodiments, the method comprises hydrating the BMP-2 / scaffold composition with water, saline, or blood before implantation, e.g., as described in Example 7. For example, the volume used to hydrate the BMP-2 / scaffold composition is proportional to the mass of the scaffold being implanted. Non-limiting examples include 0.5 to 10 mL volume hydrate (e.g., saline, blood, water) per volume in cc of space. In some embodiments, the subject is in need of a spinal fusion. In some embodiments, provided herein is a method of promoting or enhancing recovery and / or regrowth following a spinal fusion surgery, the method comprising administering to the spine or spinal fusion surgery site a composition comprising a BMP-2 and a scaffold (e.g., a calcium phosphate scaffold). In some embodiments, the spinal fusion is a lumbar interbody fusion. In some embodiments, provided herein is a method of promoting or enhancing recovery and / or regrowth following a Transforaminal Lumbar Interbody Fusion (TLIF), Lateral Lumbar Interbody Fusion (LLIF), Posterior Lumbar Interbody Fusion (PLIF), Anterior Lumbar Interbody Fusion (ALIF), Oblique Lateral Interbody Fusion (OLIF), Extreme Lateral Interbody Fusion (XLIF), Interspinous Process Fusion or Interlaminar Lumbar Instrumented Fusion (ILIF), Anterior Cervical Discectomy and Fusion (ACDF), Posterior Spinal Fusion (PSF), Posterolateral Spinal Fusion (PLF) facet fusion, interspinous fusion, or Sacroiliac Joint Fusion, the method comprising implanting a BMP- 2 / scaffold device provided herein during the surgical procedure, in the space between the fused bones. In some embodiments, the method comprises administering a BMP-2 / scaffold device herein to a subject in need thereof, wherein the subject undergoes a corpectomy or a hemicorpectomy. In some embodiments, the method comprises administering a BMP-2 / scaffold device herein to a subject in need thereof, wherein the subject undergoes corpectomy or hemicorpectomy after tumor resection. In some embodiments, the method comprises administering a BMP-2 / scaffold device herein to a subject in need thereof, wherein the subject has received treatment for cancer or tumor of the spine. In some embodiments, the method comprises administering a BMP-2 / scaffold device herein to a subject in need thereof, wherein the subject has sustained a spinal fracture, and / or undergone a surgical procedure to repair a spinal fracture. An example method comprises treating a fracture, via kyphoplasty with a BM-2 / scaffold device herein. For example, in some embodiments, provided herein is a method of promoting spinal health, reducing spinal pain, or increasing spinal stability in a subject in need thereof, the method comprising administering to the subject a composition comprising a BMP-2 and a scaffold, wherein the subject has received treatment for a fractured or surgically resected spine or vertebra. In some embodiments, the subject has received treatment for vertebral compression fractures, pars fractures or spondylolysis, bone cysts, tumors, osteoporosis, or traumatic force. In some embodiments, the method comprises administering a composition herein to a subject in need thereof, wherein the subject has sustained or received surgery of the spine in treatment of compression fractures, burst fractures, flexion-distraction fractures, fracture-dislocation. In some embodiments, the method comprises administering a BMP-2 / scaffold composition herein in a subject during a unilateral, single-level, single interbody cage, TLIF procedure (from L2-S1 with posterior supplemental fixation). In example embodiments, the composition herein is positioned within the interbody cage (e.g., a BMP-2 and / or device herein). In some embodiments, the multi-level spinal fusion (e.g., ALIF, ILIF, LLIF, PLIF, OLIF, TLIF, XLIF) involves any number of vertebrae and / or the sacroiliac bone. In some embodiments, the multi-level spinal fusion involves two, three, four, five, six, or seven vertebrae. In some embodiments, the multilevel fusion is a three- or four-level spinal fusion (e.g., ALIF, LLIF, PLIF, OLIF, TLIF, XLIF). In some embodiments, the subject undergoes a single-level spinal fusion. In some embodiments, the spinal fusion is a lumbar interbody spinal fusion. In some embodiments, the spinal fusion is a non-interbody fusion. In some embodiments, the spinal fusion is a cervical or thoracic region spinal fusion. In some embodiments, the BMP-2 / scaffold device is implanted in a subject in need thereof in a cavity in the spine. For example, in some embodiments, the cavity refers to the space between two vertebrae, or between a vertebra and sacroiliac bone. In some embodiments, the cavity is a gap, crack, fissure, intervertebral space, disc space, or the like. In some embodiments, the dosage of the composition herein is described in reference to a volume of the cavity to be filled. For example, in some embodiments, a dosage is provided herein as a mass of BMP-2 (mg) per cubic centimeter of space to be filled (e.g., the cavity, or a portion thereof - for example, in instances wherein the cavity is filled with an interbody cage, the volume is approximately that of the cavity minus the cage). In some embodiments, the composition is administered at 0.8 mg BMP-2 / cc scaffold. In some embodiments, the composition is administered at 2 mg BMP-2 / cc scaffold. In some embodiments, the composition is administered at 0.8 mg BMP-2 / cc cavity. In some embodiments, the composition is administered at 2 mg BMP-2 / cc cavity. In some embodiments, the composition is administered at 0.8 mg BMP-2 / cc of an interbody fusion cage space. In some embodiments, the composition is administered at 0.8 mg BMP-2 / cc of an interbody fusion cage space. In some embodiments, the BMP-2 is administered at a dose of about 0.05 to about 10 mg per cubic centimeter of space to be filled (i.e., disc space). In some embodiments, the BMP-2 is administered at a dose of about 0.08 to about 8 mg per cubic centimeter of space to be filled. In some embodiments, the BMP-2 is administered at a dose of about 0.1 to about 7 mg per cubic centimeter of space to be filled. In some embodiments, the BMP-2 is administered at a dose of about 0.2 to about 5 mg per cubic centimeter of space to be filled. In some embodiments, the BMP-2 is administered at a dose of about 0.5 to about 3 mg per cubic centimeter of space to be filled. In some embodiments, the BMP-2 is administered at a dose of about 0.6 to about 2.5 mg per cubic centimeter of space to be filled. In some embodiments, the BMP-2 is administered at a dose of about 0.8 to about 2.0 mg per cubic centimeter of space to be filled. In some embodiments, the BMP-2 is administered at a dose of 0.7 mg / cc to 0.9 mg / cc. In some embodiments, the BMP-2 is administered at a dose of about 0.8 mg / cc. In some embodiments, the BMP-2 is administered at a dose of about 2.0 mg / cc. In some embodiments, the BMP-2 is administered at a dose of 0.3 mg / cc, 0.4 mg / cc, 0.5 mg / cc, 0.6 mg / cc, 0.7 mg / cc, 0.8 mg / cc, 0.9 mg / cc, 1.0 mg / cc, 1.1 mg / cc, 1.2 mg / cc, 1.3 mg / cc, 1.4 mg / cc, 1.5 mg / cc, 1.6 mg / cc, 1.7 mg / cc, 1.8 mg / cc, 1.9 mg / cc, 2.0 mg / cc, 2.1 mg / cc, 2.2 mg / cc, 2.3 mg / cc, 2.4 mg / cc, 2.5 mg / cc, 2.6 mg / cc, 2.7 mg / cc, 2.8 mg / cc, 2.9 mg / cc, or 3.0 mg / cc. In some embodiments, provided herein is a method of providing supportive care for an anterior spinal fusion procedure (e.g., ALIF, LLIF, or OLIF), wherein the method comprises accessing a spinal disc space through a retroperitoneal space, and placing a single, similarly sized cage packed with a BMP-2 / scaffold composition disclosed herein. In some embodiments, provided herein is a method of providing supportive care for a posterior spinal fusion procedure (e.g., TLIF, or PLIF), wherein the method comprises accessing an anterior portion of a spinal disc space and placing one or more cages packed with a composition disclosed herein (e.g., BMP-2 / scaffold) in the anterior portion of the disc space or diagonally across the disc space. In some embodiments, the composition further comprises a bone graft or bone graft product. In some embodiments, the cage further comprises demineralized bone matrix and / or mineralized allograft chips. Subjects In some embodiments, the subject has back pain. In some embodiments, the subject has back pain due to injury, degenerative disc disease, cancer, surgery, inflammation, misalignment, scoliosis, osteoporosis, joint decay, or the like. In some embodiments, the subject has degenerative disc disease, cancer, scoliosis, or osteoporosis. In some embodiments, the subject has degenerative disc disease. In some embodiments, the subject has scoliosis. In some embodiments, the subject is undergoing spinal fusion or spine surgery to stabilize or fill a backjoint. In some embodiments, the subject has lumbar degeneration (e.g., lumbar degenerative disc disease). In some embodiments, the subject has cervical degeneration. In some embodiments, the subject has thoracic degeneration. In some embodiments, the subject has sacroiliac joint degeneration. In some embodiments, the subject has received a single level lumbar spinal fusion between L2 and SI. In some embodiments, the subject is skeletally mature and is diagnosed with degenerative disc disease (DDD) requiring fusion at a single lumbar level. The lumbar degeneration may be symptomatic, e.g., back and / or radicular pain with or without foraminal or recess stenosis. The symptoms may be confirmed by patient history, physical examinations, or radiographic imaging (Xray, CT, MRI), or a combination thereof. The subject may have no more than Grade 2 Spondylolisthesis. The subject may have instability as defined by > / -3mm translation or > / -5° angulation. The subject may have osteophyte formation of facet joints or vertebral endplates. The subject may have decreased disc height, e.g., on average by >2mm, which may be dependent upon the spinal level. The subject may have scarring / thickening of ligamentum flavum, annulus fibrosis, or facet joint capsule, or a combination thereof. The subject may have a herniated nucleus pulposus. The subject may have facet joint degeneration / changes. The subject may have vacuum phenomenon. The subject may have a preoperative ODI score >35 at pre-op / baseline. The subject may have preoperative back and / or leg pain score of >4 (out of 10). The subject may have failed >6 months non-operative / conservative treatment (e.g., physical therapy, bracing, traction, medication, TENS, and / or spinal injections). In some cases, the subject does not have osteoporosis as defined as a T score < / - 2.5 from a DEXA scan. In some embodiments, the subject does not require spinal fusion surgical procedure (ALIF, LLIF, or TLIF) at more than one level (non-fusion surgery at the non-index levels, including discectomy and / or single level foraminotomy or laminectomy). In some embodiments, the subject has not had a prior spinal fusion surgical procedure at the involved or adjacent spinal levels. In some embodiments, the subject has not had a prior non-fusion stabilizing surgery, e.g., interlaminar devices, dynamic stabilization, or disc replacements. In some embodiments, the subject had a prior non-fusion surgery at the target levels, including discectomy and / or single level foraminotomy or laminectomy. In some embodiments, the subject does not have greater than a Grade 2 Spondylolisthesis. In some embodiments, the subject is not currently treated with an internal or external bone growth stimulator. In some embodiments, the subject does not have osteoporosis to a degree that spinal instrumentation is contraindicated. In some embodiments, the subject does not have a history of a traumatic vertebral fracture. In some embodiments, the subject is not morbidly obese, as defined by a Body Mass Index (BMI) >40. In some embodiments, the subject does not have an overt or active bacterial infection, either local or systemic. In some embodiments, the subject does not use, or has not used within 30 days of treatment, tobacco or nicotine. In some embodiments, the subject does not use, or has not used within 30 days of treatment steroids (e.g., cortisone). In some embodiments, the subject does not have a comorbidity precluding the subject from being a surgical candidate. In some embodiments, the subject does not have a systemic disease, e.g., Lupus disease, Reiter's disease, Rheumatoid disease, AIDS, HIV, hepatitis, or autoimmune disease that requires immunosuppressive therapy, including biologies, for systemic inflammation. In some embodiments, the subject does not have a history of malignancy, radiotherapy, or chemotherapy for any malignancy within the last 5 years. A history of malignancy may include multiple exostoses syndrome (also known as multiple osteochondromas syndrome). In some embodiments, the subject does not have an inherited condition associated with bumps of cartilage on the bones. In some embodiments, the subject does not have an increased risk of chondrosarcoma. In some embodiments, the subject has not undergone any transplant surgery. In some embodiments, the subject is not on immunosuppressant therapy. In some embodiments, the subject does not have a history of any endocrine or metabolic disorder known to affect osteogenesis (e.g.: Paget's disease, renal osteodystrophy, Ehler-Danlos syndrome, or osteogenesis imperfecta). In some embodiments, the subject does not have insulin dependent diabetes. In some embodiments, the subject does not have an HbAlc value of greater than 7. In some embodiments, the subject does not have insulin dependent diabetes or an HbAlc of greater than 7.0. In some embodiments, the subject does not have a history of exposure to any recombinant proteins or peptides used for bone formation. In some embodiments, the subject does not have hypersensitivity or allergy to a BMP, tricalcium phosphate, and / or instrumentation materials (including but not limited to titanium, titanium alloy, PEEK). In some embodiments, the subject does not have a history of any allergy resulting in anaphylaxis. In some embodiments, the subject is not currently taking any drug known to interfere with bone / soft tissue healing. In some embodiments, the subject does not require: a secondary surgical intervention within 24 months of administration. In some embodiments, after administration the neurological status of the subject is maintained or improved. In some embodiments, the subject’s Oswestry Disability Index is decreased after administration. In some embodiments, the subject’s pain is reduced after the administration (e.g., 24 months after administration as compared to before administration). In some embodiments, the subject has bone fusion as assessed by radiographic fusion assessment (e.g., CT). In some embodiments, the subject has the presence of bridging bone (e.g., as assessed by CT). In some embodiments, the subject exhibits an outcome measurement as provided in Example 4. In some embodiments, the subject meets an inclusion criteria of Example 4. In some embodiments, the subject does not meet an exclusion criteria of Example 4. Compositions In one aspect, provided herein are compositions comprising a scaffold that may be delivered (e.g., implanted) into a subject. The compositions may be positioned within an optional interbody cage. In some embodiments, the compositions comprise a BMP-2 tethered to the scaffold. In some embodiments, the BMP-2 is non-covalently tethered to the scaffold. In some embodiments, the BMP-2 comprises binding peptides that bind to (tether to) a ceramic scaffold. In some embodiments, the BMP-2 comprises one or more calcium binding peptides tethered to a calcium-containing scaffold. In some embodiments, the BMP-2 is chelated to the scaffold. In some embodiments, the BMP-2 is bonded to the scaffold (e.g., via ceramic bond(s), non-covalent bond(s), chelation interaction(s), hydrogen bond(s), ionic bond(s), or covalent bond(s)). In some embodiments, the BMP-2 is bonded to the scaffold via a calcium-binding peptide / calcium interaction. In some embodiments, the BMP-2 is bonded to a calcium coating on a calcium-coated scaffold. Non-limiting example compositions are shown in FIGS. 1A and IB. FIGS. 1A and IB show an example embodiment of a composition comprising a tethered BMP-2 and a scaffold within an interbody cage (in some embodiments, collectively referred to as an interbody fusion device). The composition may comprise a scaffold described herein. For example, a scaffold comprising a calcium containing compound, such as calcium phosphate. In some embodiments, the composition comprises a BMP-2 implant without a cage. In some embodiments, the BMP-2 is an amorphous or moldable implant. In some embodiments, the BMP-2 is a rigid implant. In some embodiments, the BMP-2 is non-covalently bound to a support or scaffold. In some embodiments, the BMP-2 is bound to a support or scaffold through the interaction of one or more binding peptide domains with the scaffold. In some embodiments, the scaffold comprises calcium phosphate. In some embodiments, the calcium phosphate (CaP) scaffold is a filamentous or cotton-like scaffold. In some embodiments, the calcium phosphate (CaP) scaffold is a 3D printed scaffold. In some embodiments, the calcium phosphate (CaP) scaffold is a sponge-like scaffold. In some embodiments, the calcium phosphate (CaP) scaffold comprises porous nanostructures. In some embodiments the CaP is present as a coating onto another implant. In some embodiments, the calcium phosphate (CaP) scaffold comprises P-tri-calcium phosphate (P-TCP), i.e., CasOsP?. In some embodiments, the composition comprises BMP-2 non-covalently affixed to a scaffold, wherein the scaffold is provided in combination with a medical tool used in spinal surgery. For example, in some embodiments, provided herein is a BMP-2 affixed to a scaffold, wherein the scaffold is implanted in combination with (i.e., within 24 hours of) a spinal screw, spinal rod, spinal plate, spinal cage, spinal wedge, or other spinal implant or fastener. In some embodiments, the composition comprises a BMP-2, a scaffold, and a means for stabilizing a spinal fusion (e.g., a cage, screw, rod, plate, bag, disc, wedge, etc.). In some embodiments, the composition comprises a BMP-2, a calcium phosphate scaffold (e.g., P TCP), and a spinal fusion implant or fastener. In some embodiments, the spinal fusion implant or fastener is a pedicle screw and / or a rod system that is cleared by the United States Food and Drug Administration, or any other international regulatory body. Scaffolds In one aspect, provided herein are scaffolds that may be delivered to a subject, for example, in a method described herein. For instance, the scaffolds may be delivered to the subject within an optional interbody cage as part of an interbody fusion device. Alternatively, the scaffolds may be delivered to the subject without an interbody cage. The scaffolds may be part of a device further comprising a BMP-2. As a non-limiting example, the BMP-2 is bound to the scaffold. The scaffold or device may generate bone in the subject. In some embodiments, a scaffold herein comprises a calcium containing compound. Nonlimiting exemplary scaffold materials include calcium phosphate (e.g., tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate), hydroxyapatite, fluorapatite, bone (e.g., demineralized bone), glasses (bioglasses) such as silicates, vanadates, and related ceramic minerals, and chelated divalent metal ions. Specific example scaffolds include, without limitation, Mastergraft strip, Vitoss Foam Pack, chronOS Strip, Vitoss Micromorsels, LifeInk500, Hyperelastic Bone, bioactive glass, P TCP powder, P TCP spray dried powder, hydroxyapatite powder, hydroxyapatite-coated bone screw, P TCP granules, hydroxyapatite granules, 3D printed scaffolds, and ReBOSSIS. Scaffolds herein may be of any form, including, without limitation, a granular form, a porous form, a powder, a putty (e.g., a moldable putty), a paste, fiber form, a coating on a solid surface (e.g., a coating on a medical device), and any combination thereof. In some embodiments, the scaffold is a fiber. The fiber may be an electrospun fiber. In some embodiments, the fiber comprises a calcium containing compound and a bioabsorbable polymer. Example fibers include about 0-40 wt% bioabsorabable and 60-100% calcium containing compound. The calcium containing compound may comprise calcium phosphate, e.g, betatricalcium phosphate. The calcium containing compound may comprise calcium phosphate and silicon-doped vaterite (SiV). The bioabsorbable polymer may be PLGA. In some embodiments, the fiber comprises about 20-40% bioabsorbable polymer and about 60-80% calcium containing compound. In some embodiments, the fiber comprises about 30% bioabsorbable polymer and about 70% calcium containing compound. The scaffolds may be a variety of different shapes (e.g., a cross, a ladder, a sphere, an ellipsoid, a square, a triangular pyramid, a rod, a cone, a torus, or a wedge, or any combination thereof) and sizes (e.g., largest average diameter of about 1 mm to about 10 cm). In some embodiments, the scaffold is porous (e.g., about 90% to about 99% porous when dry (no hydration)). Interbody Fusion Device In some embodiments, the composition comprises a BMP-2 and a scaffold within an implantable cage. An implantable cage may be a static cage, or an expandable cage. The implantable cage may be an interbody cage. In some embodiments, the BMP-2 and scaffold are provided within, around, or otherwise affixed to an anterior cage, a posterior cage, an interbody cage, an expandable cage, a corpectomy cage, a biodegradable cage, an artificial disc, or a grafted cage. In some embodiments, the cage is a metal cage such as a titanium cage. A cage may come in a variety of sizes, including but not limited to disc-shaped, screw-shaped, wedge-shaped, plateshaped, cylindrical, rectangular, banana-shaped, mesh, trapezoidal, threaded, etc. In some embodiments, the cage is a polymeric cage comprising polyetheretherketone (PEEK). In some embodiments, the cage is a biocompatible cage comprising 3D-printed bone or bone-like material. In some embodiments, provided herein is a device comprising a composition herein and an interbody cage. In some embodiments, the cage is used to stabilize the disk space at the time of the spinal fusion procedure. The shape and dimensions of the device may be appropriate for the procedure and the patient’s anatomy. The materials of the cage may include titanium, polyetheretherketone (PEEK), polyetherketoneketone (PEKK), carbon fiber, grafted or synthetic bone, cartilage, or any combination thereof. In some embodiments, the cage is a 3D printed using a porous material or design. For example, in some embodiments, the cage is a 3D printed porous titanium cage. In some embodiments, the cage is a 3D printed carbon fiber cage. In some embodiments, the cage is a PEEK polymer cage. The PEEK cages are generally biocompatible, radiolucent, and have modulus of elasticity similar to the bone. The interbody cage may provide disc space distraction and temporary stabilization while fusion occurs. Non-limiting examples include Medtronic's CAPSTONE® and CAPSTONE PTC® Spinal Systems ((K073291, K133205), Globus Medical's SUSTAIN-0 spacers (K130478, K143578) and DePuy Spine's CONDUIT Interbody Platform / EIT Cellular Titanium (K170503, K201605). Additional examples of compatible cages include the Pulsar™ Expandable TLIF / PLIF Implant, PROCAYMAN™ Expandable PLIF Peek Cage, Procida PLIF 3D Printed Titanium Cage, Ustica TLIF 3D Printed Titanium Cage, Alligator Expandable PLIF cage, AccuLIF® Expandable Lumbar interbody devices, including AccuLIF TL and AccuLIF PL, AIRO CAGE Expandable Interbody Device, ARIA Expandable PLIF Cage, ALTERA® articulating expandable TLIF spacer, BERKUDA® X expandable cage, CALIBER® expandable lumbar fusion device, Concorde Lift Expandable Cage, Catalyft™ PL40 expandable titanium interbod, Crea PLIF Expandable Cage, Capella-X Expandable Cage, DIONYS™ PLEC Posterior Lumbar Expandable Cage, Elite™ Expandable Interbody Fusion System, ELEVATE™ Spinal System, eZspand™, eFuse® expandable interbody cages, dualX™ Dual Expanding Interbody Fusion System, Explorer® TO Expandable Interbody System, FlareHawk9™ multidirectional expandable lumbar fusion device, FlareHawk7™ multidirectional expandable lumbar fusion device, FORZA® XP Expandable Spacer System, FLXfitl5™ expandable, articulated interbody fusion device (IBFD), Half Dome X Posterior Lumbar Interbody Spacer System, IO™ Expandable Lumbar Interbody Fusion System, KLIMT™ Expandable Lumbar Interbody Fusion Cage, L-VARLOCK® lumbar cage, LorX® Expandable PLIF Peek Cage, Luna 360 Interbody Fusion System, Luna XD, Leva® PX Interbody Device, The Leva™ Interbody Device expandable titanium implant, The Lucent XP Expandable Interbody device, The Omega XP Expandable Lumbar Interbody Device, LATIS® expandable lumbar interbody fusion spacer, Monaco 3D printed expandable TLIF / PLIF Interbody Device, MOJAVE™ PL 3D Expandable Interbody System, MLX, Pylon, Pronaos, PROLIFT® Expandable Spacer System, PROLIFT® Micro Expandable Spacer System, PROLIFT® Wedge Implant System, RODIN™ expandable titanium lumbar interbody fusion implants, RISE® titanium expandable lumbar fusion device, RISE® IntraLIF® expandable lumbar interbody spacer, SABLE™ expandable posterior lumbar interbody spacer, Spinal Jaxx expandable lumbar fusion device, SPineology® OptiMesh® Expandable Interbody Fusion System, StaXx® IB Expandable Interbody Device, TRAN-C expandable interbody cage, TLX® 15, 20 expandable implant, TiBOW Expandable Spacer System, or Twist Duo: Expandable & Modular Cage. In some embodiments, the interbody cage is aNuVasive CoRoent XL or NuVasive COHERE PEEK cage. In some embodiments, the interbody cage is a Stryker Cascadia or Medtronic Titan Endoskeleton titanium cage. In some embodiments, the interbody cage is a Spinal Elements Magnum+ or SeaSpine Nanometalene titanium-coated PEEK cage. In some embodiments, the interbody cage is a PEEK cage selected from Stryker Aleutian Curved PEEK, Globus Medical Sustain - O PEEK, and Orthofix Forza PEEK. In some embodiments, the interbody cage is a titanium cage selected from Stryker Cascadia Titanium, Stryker Juliet Titanium, and Depuy Spine CONDUIT Titanium. In some embodiments, the interbody cage is a titanium-coated PEEK cage, Medtronic CAPSTONE PTC. In some embodiments, provided herein is an interbody cage comprising a BMP-2 and scaffold composition disclosed herein, wherein the interbody cage has a heigh of about 5 to about 20 mm and / or an internal volume of about 0.1 to about 20.0 cc. In some embodiments, provided herein is an interbody cage comprising a BMP-2 and scaffold composition disclosed herein, wherein the interbody cage has a heigh of about 7 to about 15 mm and / or an internal volume of about 1.0 to about 10.0 cc. In some embodiments, the interbody cage is an ALIF or LLIF interbody cage. In some embodiments, the interbody cage is a 510(k)-cleared ALIF or LLIF interbody cage. In some embodiments, the composition herein is implanted in an ALIF / LLIF interbody cage comprising a BMP-2 and scaffold composition disclosed herein, wherein the ALIF / LLIF interbody cage has a heigh of about 8 to about 14 mm and / or an internal volume of about 1.0 to about 8.0 cc. In some embodiments, the interbody cage is a TLIF interbody cage. In some embodiments, the interbody cage is an ALIF or LLIF interbody cage. In some embodiments, the interbody cage is a 510(k)-cleared TLIF interbody cage. In some embodiments, the composition herein is implanted in a TLIF interbody cage comprising a BMP-2 and scaffold composition disclosed herein, wherein the TLIF interbody cage has a heigh of about 6 to about 16 mm, and / or a width of about 8 to about 12 mm, and / or a length of about 22 to about 36 mm, and / or an internal volume of about 0.2 to about 2.2 cc. BMP-2 In some embodiments, the BMP-2 is a mature peptide of BMP-2 (e.g., does not comprise a signal sequence). In some embodiments, the BMP-2 is a functional portion of a native human BMP-2. 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 : QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNS TNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR (SEQ ID NO: 442). In some embodiments, the BMP-2 comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 442. In some embodiments, the BMP-2 comprises a sequence at least about 90% identical to SEQ ID NO: 442. In some embodiments, the BMP-2 comprises SEQ ID NO: 442. In certain embodiments, use of BMP-2 herein includes a BMP-2 molecule comprising BMP-2 (e.g., of SEQ ID NO: 442) and one or more binding proteins. The BMP-2 may also be referred to as a BMP-2 fusion protein or recombinant BMP-2 protein. In some embodiments, the BMP-2 is a non-human BMP-2. The non-human BMP-2 may be homologous to a human BMP-2. In some embodiments, a non-human BMP-2 is homologous to a human BMP-2 if the non-human BMP-2 is at least about 80% identical to the human BMP-2 as determined using the NCBI Blast alignment algorithm as of the date of this filing. In some cases, the coverage is at least about 90%. In some embodiments, a non-human BMP-2 is homologous to a human BMP-2 if the non-human BMP-2 is at least about 80% positive as compared to the human BMP-2 as determined using the NCBI Blast alignment algorithm as of the date of this filing. In some cases, the coverage is at least about 90%. In some embodiments, a nonhuman BMP-2 is homologous to a human BMP-2if the non-human BMP-2 aligned with the human BMP-2 using the NCBI Blast as of the date of this filing has an E value of less than about IE-40, at least about IE-50, IE-60, IE-70, or IE-10, with a query cover of at least about 90%. Targeting moieties In some embodiments, the composition herein (e.g., BMP-2, device) comprises a targeting moiety that tethers the BMP-2 to the scaffold. In some embodiments, the targeting moiety is connected to the BMP-2, and the moiety non-covalently binds to the scaffold. As a non-limiting example, the targeting moiety is covalently connected to the BMP-2 via a peptide bond. For instance, targeting moiety comprises a targeting peptide, and the targeting peptide is linked to the BMP-2 via a peptide bond. In some embodiments herein, a targeting moiety is referred to as a binding peptide, or vice versa. In some embodiments, the targeting moiety has an affinity for the scaffold, or a component of the scaffold, e.g., to a ceramic material of the scaffold such as calcium phosphate. In some embodiments, the dissociation constant (KD) for binding between the targeting moiety and the scaffold or component thereof is: (i) at least about 1 fM, at least about 10 fM, at least about 100 fM, or at least about 1 pM; and (ii) less than about 100 pM, less than about 90 pM, less than about 80 pM, less than about 70 pM, less than about 60 pM, less than about 50 pM, less than about 40 pM, less than about 30 pM, less than about 20 pM, less than about 10 pM, less than about 5 pM, less than about 1 pM, or less than about 100 pM. For example, the targeting moiety may bind to beta-tricalcium phosphate with an affinity of about 100 fM to about 100 pM, about 1 pM to about 100 pM, about 10 pM to about 100 pM, about 100 pM to about 100 pM, or about 1 pM to about 100 pM. In some embodiments, the targeting moiety comprises one or more targeting peptides that each bind to the scaffold. In some embodiments, the targeting peptide binds to the ceramic material of the scaffold. For example, the targeting peptide binds to calcium phosphate (e.g., tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate), hydroxyapatite, fluorapatite, bone (e.g., demineralized bone), glasses (bioglasses) such as silicates, vanadates, and related ceramic minerals, or chelated divalent metal ions, or a combination thereof. In some embodiments, the targeting peptide comprises two or more targeting peptides. In some embodiments, two or more targeting peptides is no more than about 50, 45, 40, 35, 30, 25, 20, 15, or 10 targeting peptides. In some embodiments, two or more targeting peptides is about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, or 30 targeting peptides. In some embodiments, two or more targeting peptides is about 2 to about 10 targeting peptides. In some embodiments, two or more targeting peptides is about 5 targeting peptides. In some embodiments, the targeting peptide 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 peptide 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 peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 3. In some embodiments, the targeting peptide 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 peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 5. In some embodiments, the targeting peptide 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 peptide 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 peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 8. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 9. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 10. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 11. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 12. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 13. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 14. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 15. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 16. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 17. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 18. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 19. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 20. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 21. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 22. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 23. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 24. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 25. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 26. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 27. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 28. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 29. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 30. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 31. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 32. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 33. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 34. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 35. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 36. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 37. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 38. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 39. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 40. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 41. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 42. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 43. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 44. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 45. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 46. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 47. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 48. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 49. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 50. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 51. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 52. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 53. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 54. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 55. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 56. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 57. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 58. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 59. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 60. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 61. Table 1. Targeting Peptides Sequence SEQ ID NO: LLADTTHHRPWT 1 VIGESTHHRPWS 2 LIADSTHHSPWT 3 ILAESTHHKPWT 4 ILAETTHHRPWS 5 IIGESSHHKPFT 6 GLGDTTHHRPWG 7 VLGDTTHHKPWT 8 IVADSTHHRPWT 9 STADTSHHRPS 10 TSGGESTHHRPS 11 TSGGESSHHKPS 12 TGSGDSSHHRPS 13 GSSGESTHHKPST 14 VGADSTHHRPVT 15 GAADTTHHRPVT 16 AGADTTHHRPVT 17 GGADTTHHRPAT 18 GGADTTHHRPGT 19 LLADTTHHRPWTVIGESTHHRPWS 20 LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFT 21 LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWT 22 LLADTTHHRPWTILAESTHHKPWT 23 LLADTTHHRPWTILAESTHHKPWTLLADTTHHRPWTILAESTHHKPWTLLADTTHHRPW T 24 LLADTTHHRPWTGLGDTTHHRPWG 25 LLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRPWT 26 LLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRP WT 27 LLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRPWTGLGDTTHHRPWGLLADTTHHRP WTGLGDTTHHRPWGLLADTTHHRPWT 28 STADTSHHRPSTSGGESTHHRPSTSGGESSHHKPSTGSGDSSHHRPSGSSGESTHHKPST 29 VGADSTHHRPVTGAADTTHHRPVTAGADTTHHRPVTGGADTTHHRPATGGADTTHHRP GT 30 STADTSHHRPSLLADTTHHRPWTTSGGESTHHRPSVGADSTHHRPVTTSGGESSHHKPSG AADTTHHRPVTTGSGDSSHHRPSGSSGESTHHKPSTGGADTTHHRPAT 31 AAADTTHHRPWT 32 AAADTTHHRPWTAAADTTHHRPWTAAADTTHHRPWTAAADTTHHRPWTAAADTTHH RPWT 33 LLADAAHHRPWTLLADAAHHRPWTLLADAAHHRPWTLLADAAHHRPWTLLADAAHH RPWT 34 LLADTTAARPWTLLADTTAARPWTLLADTTAARPWTLLADTTAARPWTLLADTTAARP WT 35 LLADTTHHRPWTLLADTTHHRPWT 36 LLADTTHHRPWTLLADTTHHRPWTLLADTTHHRPWT 37 LLADTTHHRPWTLLADTTHHRPWTLLADTTHHRPWTLLADTTHHRPWTLLADTTHHRP WT 38 STSGSTVIGESTHHRPWSLIADSTHHSPWTILAESTHHKPWTILAETTHHRPWSIIGESSHH KPFTGLGDTTHHRPWGVLGDTTHHKPWTIVADSTHHRPWTGQVLPTTTPSSPSTTSGS 39 LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWG 40 VIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWT 41 (X1)(X2), wherein XI comprises SEQ ID NO: 1 and X2 comprises one or more of SEQ ID NOS: 1-41. 42 (X1)(X2), wherein XI comprises SEQ ID NO: 2 and X2 comprises one or more of SEQ ID NOS: 1-41. 43 (X1)(X2), wherein XI comprises SEQ ID NO: 4 and X2 comprises one or more of SEQ ID NOS: 1-41. 44 (X1)(X2), wherein XI comprises SEQ ID NO: 6 and X2 comprises one or more of SEQ ID NOS: 1-41. 45 (X1)(X2), wherein XI comprises SEQ ID NO: 7 and X2 comprises one or more of SEQ ID NOS: 1-41. 46 (X1)(X2), wherein XI comprises SEQ ID NO: 1 and X2 comprises one or more of SEQ ID NOS: 2, 4, 6, or 7. 47 (X1)(X2), wherein XI comprises SEQ ID NO: 2 and X2 comprises one or more of SEQ ID NOS: 1,4, 6, or 7. 48 (X1)(X2), wherein XI comprises SEQ ID NO: 4 and X2 comprises one or more of SEQ ID NOS: 1,2, 6, or 7. 49 (X1)(X2), wherein XI comprises SEQ ID NO: 6 and X2 comprises one or more of SEQ ID NOS: 1,4, 2, or 7. 50 (X1)(X2), wherein XI comprises SEQ ID NO: 7 and X2 comprises one or more of SEQ ID NOS: 1,4, 6, or 2. 51 (X1)(X2), wherein XI comprises SEQ ID NO: 1 and X2 comprises two or more of SEQ ID NOS: 2, 4, 6, or 7. 52 (X1)(X2), wherein XI comprises SEQ ID NO: 2 and X2 comprises two or more of SEQ ID NOS: 1,4, 6, or 7. 53 (X1)(X2), wherein XI comprises SEQ ID NO: 4 and X2 comprises two or more of SEQ ID NOS: 1,2,6, or 7. 54 (X1)(X2), wherein XI comprises SEQ ID NO: 6 and X2 comprises two or more of SEQ ID NOS: 1,4, 2, or 7. 55 (X1)(X2), wherein XI comprises SEQ ID NO: 7 and X2 comprises two or more of SEQ ID NOS: 1,4, 6, or 2. 56 (X1)(X2), wherein XI comprises SEQ ID NO: 1 and X2 comprises three or more of SEQ ID NOS: 2, 4, 6, or 7. 57 (X1)(X2), wherein XI comprises SEQ ID NO: 2 and X2 comprises three or more of SEQ ID NOS: 1,4, 6, or 7. 58 (X1)(X2), wherein XI comprises SEQ ID NO: 4 and X2 comprises three or more of SEQ ID NOS: 1,2, 6, or 7. 59 (X1)(X2), wherein XI comprises SEQ ID NO: 6 and X2 comprises three or more of SEQ ID NOS: 1,4, 2, or 7. 60 (X1)(X2), wherein XI comprises SEQ ID NO: 7 and X2 comprises three or more of SEQ ID NOS: 1,4, 6, or 2. 61 In some embodiments, a targeting peptide comprises one or more sequences of Table 1. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a sequence of Table 1. Table 2. Additional Targeting Peptides Sequence SEQ ID NO ACAPLMFSQC 62 ACHASLKHRC 63 ACLSTKTNIC 64 ACTTPSKHQC 65 AHFSPNLLLGG 66 AHSLKSITNHGL 67 AKQTVPV 68 AKTLMPSPFPRT 69 AMSQTMTAAIEK 70 ANPPLSL 71 ANPYHRH 72 APLSLSL 73 APYHPTIPASVHGGGK 74 ASAVGSLSIRWX 75 ASGPTNV 76 ASHNPKL 77 ASWVDSRQPSAA 78 ATFSPPL 79 ATWSHHLSSAGL 80 ATWSHHLSSAGLGGGS 81 CAHLSPHKC 82 CDIPWRNEC 83 CDPLRQHSC 84 CDSLGHWLC 85 CDYTTRHSC 86 CHGTLNPEC 87 CHHNLSWEC 88 CHIWTLASC 89 CHNTFSPRC 90 CIPLHASLC 91 CITTTSLSC 92 CKLTTCKDC 93 CKNHTTFWC 94 CLKLLSRSC 95 CLLKAHPSC 96 CLNQLKQAC 97 CLSTKTNIC 98 CMNFPSPHC 99 CNYPTLKSC 100 CPQLTVGQHRT 101 CPQSPTYTC 102 CPSSAIHTC 103 CPTSTARIC 104 CQASSFPSC 105 CQPYFWYRC 106 CQTLTPSIC 107 CSKLGHLWC 108 CSKTPERIX 109 CSNNNRMTC 110 CSPILSLSC 111 CSPTNFTRC 112 CSRPAMNVC 113 CSTKAYPNC 114 CSTSSCGSC 115 CSYWGHRDC 116 CTAHDANAC 117 CTANSEKTC 118 CTHPKASMC 119 CTKTINGKC 120 CTNMQSPLC 121 CTPFTKLPC 122 CTPTTDSIC 123 CTQQNGHPC 124 CTTPSKHQC 125 CTYNVAKPC 126 DKLHRLA 127 DLNYFTLSSKRE 128 DLPPTLHTTGSP 129 DMRQQRS 130 DQYWGLR 131 DSSNPIFWRPSS 132 DSSNPIFWRPSSGGGS 133 EFLGVPASLVNP 134 EPNHTRF 135 EPRRAVAAL 136 EPRRAVAEL 137 EPRREVAEL 138 EPRREVCEL 139 ESDLTHALHWLG 140 ESLKSIS 141 ETRTQLL 142 ETVCASS 143 ETYARPL 144 ETYQQPL 145 EVHSTDRYRSIP 146 FGLQPTGDIARR 147 FSMDDPERVRSP 148 FSPLHTSTYRPS 149 FTLPTIR 150 FVNLLGQ 151 GDFNSGHHTTTR 152 GGGAAAA 153 GIHVPWMPPVAF 154 GIHVPWMPPVAFGGGS 155 GPSNNLPWSNTP 156 GSAGLKYPLYKS 157 GSCPPKK 158 GSLFKAL 159 GTQTPQP 160 GTSRLFS 161 GVHKHFYSRWLG 162 HAPLTRSPAPNL 163 HAPVQPN 164 HGSLTTLXRYEP 165 HHFHLPKLRPPV 166 HHQRSPA 167 HHTWDTRIWQAF 168 HMLAQTF 169 HNVTTRTQRLMP 170 HPTTPIHMPNF 171 HQFISPEPFLIS 172 HQFPXSNLVWKP 173 HQWDHKY 174 HRDPXSXPSAXRP 175 HRLGHMS 176 HSACHASLKHRC 177 HSACKLTTCKDG 178 HSACLSTKTNIC 179 HSMPHMGTYLLT 180 HSTGPTR 181 HTLLSTT 182 HYPTVNF 183 IAHVPETRLAQM 184 IFSMGTALARPL 185 IGYPVLP 186 INFQFLKPSTTR 187 INKHPQQVSTLL 188 IQHQAKT 189 IRXLXIS 190 ISPSHSQAQADL 191 KAFDKHG 192 KATITGM 193 KEIPPIPLLAPS 194 KEIPPIPLLAPSGGGS 195 KIPKACCVPTELSAISMLYL 196 KIPKAS SVPTELSAIATLYL AAAAEPRRAVAAL 197 KIPKAS SVPTELSAISTLYL 198 KIPKAS SVPTELSAISTLYL AAAAEPRRAVAAL 199 KIPKAS SVPTELSAISTLYL AAAAEPRRAVAEL 200 KIPKAS SVPTELSAISTLYL AAAAEPRREVAEL 201 KIPKAS SVPTELSAISTLYL AAAAXPRRXVAXL 202 KIPKAS SVPTELSAISTLYL XPRRXVAXL 203 KLHASLA 204 KLSAWSF 205 KLTWQELYQLKYKGI 206 KLTWQELYQLKYKGIGGG AAAAEPRREVAEL 207 KMNHMPN 208 KPMQFVH 209 KTSSWAN 210 LASTTHV 211 LDYPIPQTVLHH 212 LFAAVPSTQFFR 213 LGFDPTSTRFYT 214 LGPGKAF 215 LKPFSGA 216 LLADTTHHRPWP 217 LLADTTHHRPWT 218 LLADTTHHRPWTGGGS 219 LLPLKFK 220 LPFQPPI 221 LPLTPLP 222 LPRDLHATPQQI 223 LPSIHNL 224 LPWAPNLPDSTA 225 LPWTEPSFWRTP 226 LPWTEPSFWRTPGGGS 227 LQKSPSL 228 LQPSQPQRFAPT 229 LRAFPSLPHTVT 230 LSAPMEY 231 LSKNPLL 232 LSLRASAATDFQ 233 LSPPMQLQPTYS 234 LTPTMFNMHGVL 235 LTQTLQY 236 MHNVSDSNDSAI 237 MKVHERS 238 MPQTLVLPRSLL 239 MQFTPAPSPSDH 240 MTSQTLR 241 MYPLPAP 242 NERQMEL 243 NFAMNLR 244 NITQLGS 245 NKPLSTL 246 NNVSQKWQQRLI 247 NNVSQKWQQRLIGGGS 248 NPDHPDIPQDVHGGGK 249 NPMIMNQ 250 NPQMQRS 251 NPRSQAT 252 NPYAPTIPQSVAGGGK 253 NPYHPTIPQSVH 254 NPYHPTIPQSVHGGGK 255 NSMIAHNKTRMH 256 NSMIAHNKTRMHGGGS 257 NSSMLGMLPSSF 258 NTSSSQGTQRLG 259 NTTTDIPSPSQF 260 NYPTLKS 261 NYSHLRVKLPTP 262 NYSHLRVKLPTPGGGS 263 PAKQKAH 264 PDIPLSR 265 PGQWPSSLTLYK 266 PHNPGKL 267 PIDAFFD 268 PLTQPSH 269 PPKDSRG 270 PPNMARA 271 PSMKHWR 272 PTNKPHT 273 PTTMTRW 274 PTTWGHL 275 PXGPXGPXGPXGPXGPXA PXGPXGPXGPXGPXGPXG 276 QHNFRGASSSAP 277 QIPQMRILHPYG 278 QIQKPPRTPPSL 279 QLTQTMWKDTTL 280 QNLPPERYSEAT 281 QNPRQIY 282 QNYLLPK 283 QPGLWPS 284 QRSWTLDSALSM 285 QRSWTLDSALSMGGGS 286 QSLSFAGPPAWQ 287 QSSYNPI 288 QTHARHQ 289 QTHSSLW 290 QTTMTPLWPSFS 291 RCMSEVISFNCP 292 RHTLPLH 293 RPHTITN 294 RSPYYNKWSSKF 295 RTPLQPLEDFRP 296 SAGHIHEAHRPL 297 SAISDHRAHRSH 298 SAKGRAD 299 SAKKVFS 300 SASGTPS 301 SEPTYWRPNMSG 302 SFAPDIKYPVPS 303 SFQSMSLMTLVV 304 SFWHHHSPRSPL 305 SGHQLLLNKMPN 306 SGHQLLLNKMPNGGGS 307 SIFAHQTPTHKN 308 SIPKMIPTESLL 309 SIPSHSIHSAKA 310 SIRTSMNPPNLL 311 SKTSSTS 312 SLLTPWL 313 SLPHYIDNPFRQ 314 SLSKANILHLYG 315 SLVTADASFTPS 316 SMAAKSS 317 SMVYGNRLPSAL 318 SMYDTHS 319 SPEMKPR 320 SPNFSWLPLGTT 321 SPNLPWSKLSAY 322 SPNNPRE 323 SPNNTRE 324 SPSLMARSSPYW 325 SQHSTQD 326 SQTLPYSNAPSP 327 SRTGAHH 328 SSHHHRH 329 SSPPRVY 330 SSSMAKM 331 SSTLKTFFGFPD 332 SSTLKTFFGFPDGGGS 333 SSTQAHPFAPQL 334 SSTQVQHTLLQT 335 SSVPGRP 336 SSYEYHA 337 STLASMR 338 STPNSYSLPQAR 339 STQAHPW 340 STSAKHW 341 STVVMQPPPRPA 342 SVFLPTRHSPDL 343 SVQTRPLFHSHF 344 SVSVGMKPSPRP 345 SVSVGMNAESXA 346 SVSVGMNAESYG 347 SVSVGTEAESXA 348 SWPLYSRDSGLG 349 SYIDSMVPSTQT 350 SYKTTDSDTSPL 351 SYSQMDPPRSLPGGGS 352 TAAASNLRAVPP 353 TAPLSHPPRPGA 354 TDHPPKA 355 TGLAKTA 356 TGLLPNSSGAGI 357 TGPPSRQPAPLH 358 TGPTSLS 359 THPVVFEDERLF 360 TIHSKPA 361 TKDWLPS 362 TLAFQTA 363 TLAPTFR 364 TLDKYTRLLSRY 365 TLGLPML 366 TLLRTQV 367 TLMTTPP 368 TLPSPLALLTVH 369 TLQRMGQ 370 TLSNGHRYLELL 371 TMGFTAPRFPHY 372 TMRNPITSLISV 373 TMRNPITSLISVGGGS 374 TMTNMAK 375 TPLSYLKGLVTV 376 TPLTSPSLVRPQ 377 TPSPKLLQVFQA 378 TPSTGLGMSPAV 379 TPVYSLKLGPWP 380 TQTWPQSSSHGL 381 TRFYDSL 382 TRLVPSRYYHHP 383 TSPIPQMRTVPP 384 TTKNFNK 385 TTLSPRT 386 TTNSSMTMQLQR 387 TTTLPVQPTLRN 388 TTTWTTTARWPL 389 TTYNSPP 390 TVAQMPPHWQLT 391 TVLGTFP 392 TWNSNSTQYGNR 393 TWTLPAMHPRPA 394 VHLTHGQ 395 VHPRPSL 396 VHTSLLQKHPLP 397 VLPNIYMTLSA 398 VMDFASPAHVLP 399 VNQEYWFFPRRP 400 VPPISXTFLFXSTXS 401 VPPLHPALSRXN 402 VSPFLSPTPLLF 403 VSRLGTPSMHPS 404 VVKSNGE 405 VYSSPLSQLPR 406 WLPPRTQ 407 WPANKLSTKSMY 408 WPFNHFPWWNVP 409 WPTYLNPSSLKA 410 WSAHIVPYSHKP 411 WWPNSLNWVPRP 412 WYPNHLA 413 XITXGAY 414 XPRRAVAAL 415 XPRRAVAXL 416 XPRRXVAXL 417 XXFPLXG 418 YATQHNWRLKHE 419 YCPMRLCTDC 420 YELQMPLTLPLN 421 YEPAAAE 422 YGKGFSPYFHVT 423 YPHYSLPGSSTL 424 YPIMSHTCCHGV 425 YPKALRN 426 YPSLLKMQPQFS 427 YQPRPFVTTSPM 428 YSAPLARSNVVM 429 YTRLSHNPYTLS 430 YTTHVLPFAPSS 431 YTWQTIREQYEM 432 In some embodiments, a targeting peptide comprises one or more sequences of Table 2. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a sequence of Table 2. Additional targeting peptides useful in the present disclosure include any one of SEQ ID NO: 1 to SEQ ID NO: 558 of US 7,572,766. In some embodiments, the targeting peptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to any one of SEQ ID NO: 1 to SEQ ID NO: 558 of US 7,572,766. In some embodiments, the device or kit comprises a chimeric polypeptide comprising the targeting peptide and a targeting moiety. In some cases, the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 433 (ASGAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTGQAKHKQRKRLKSSCKRHPL YVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKA CCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR). In some cases, the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical            to            SEQ            ID            NO:            434 (MPIGSLLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTH HKPWTASGAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTGQAKHKQRKRLKSSC KRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNS KIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR). In some cases, the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100%         identical         to         SEQ         ID         NO:         435 (LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPW TASGAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTGQAKHKQRKRLKSSCKRHPL YVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKA CCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR). In some cases, the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical            to            SEQ            ID            NO:            436 (VIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWTASGAGGSEGGG SEGGTSGATGAGTSTSGGGASTGGGTGQAKHKQRKRLKSSCKRHPLYVDFSDVGWND WIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISML YLDENEKVVLKNYQDMVVEGCGCR). In some cases, the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 437 (IIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWTASGAGGSEGGGSEGGTSGATGA GTSTSGGGASTGGGTGQAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAF YCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVL KNYQDMVVEGCGCR). In some cases, the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO: 438 (GLGDTTHHRPWGILAESTHHKPWTASGAGGSEGGGSEGGTSGATGAGTSTSGGGAST GGGTGQAKHKQRKRLKS SCKRHPLYVDF SD VGWNDWIVAPPGYHAF YCHGECPFPLA DHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEG CGCR). In some cases, the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%,   85%,   90%,   95%, or 100% identical to SEQ ID NO: 439 (ILAESTHHKPWTASGAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTGQAKHKQR KRLKS SCKRHPLYVDF SD VGWNDWIVAPPGYHAF YCHGECPFPLADHLNSTNHAIVQT LVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR). In some cases, the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID NO:      440 ((X)QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHL NSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGC R), wherein X comprises a targeting peptide and optionally a linker. For example, the targeting peptide comprises one or more of SEQ ID NOS: 1-41. In some cases, the chimeric polypeptide comprises a sequence at least about 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to SEQ ID                                  NO:                                  441 ((X)ASGAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTGQAKHKQRKRLKSSCKRH PLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIP KACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR), wherein X comprises a targeting peptide and optionally a linker. For example, the targeting peptide comprises one or more of SEQ ID NOS: 1-41. In some embodiments, a BMP-2 is not connected to a scaffold using a targeting moiety. For example, the BMP-2 may interact with the scaffold via non-covalent bonds. The BMP-2 may be connected to a scaffold by hydrogen bonding, ionic bonding, hydrophobic interactions, or van der Waals forces. The BMP-2 may also be connected to a scaffold using covalent bonds. Examples of methods for connecting using covalent bonds includes chemical linkers and spacers that are used for modifying active groups within proteins such as amines, thiols and carbohydrates. Device manufacture Further provided herein are methods of manufacturing a device comprising a scaffold (e.g., scaffold) and a BMP-2. Some methods comprise: (a) providing a first solution of a BMP-2 (e.g., a chimeric polypeptide comprising the BMP-2 and a targeting moiety), (b) providing a scaffold, and (c) combining (a) and (b). In some embodiments, the method further comprises (d) washing the scaffold of step (c) with a second solution, such as phosphate buffered saline (PBS). In some embodiments, the method further comprises drying the scaffold of step (c) or step (d). In some embodiments, the method further comprises positioning the scaffold and BMP-2 combination within an interbody cage. In some embodiments, the mass of the BMP-2 (e.g., a BMP-2 alone or a BMP-2 connected to a targeting moiety) per cubic centimeter of the scaffold in a device is between about 0.05 and 50 (mg / cc), e.g., about 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg / cc or any number therebetween. For example, the BMP-2 is about 0.5-1.5, 1.5-2.5, 0.8 or 2 mg per cubic centimeter device. One method of measuring the amount of therapeutic peptide bound to the scaffold includes: (1) measuring the mass of therapeutic peptide input in the first solution, (2) measuring the mass of the BMP-2 remaining in the first solution after combination with and removal from the scaffold, (3) measuring the mass of the BMP-2 in the second solution if a wash step is included, (4) summing (2) and (3); and subtracting the sum of (4) from (1). The terminology used herein is for the purpose of describing particular cases only and is not intended to be limiting. The singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. To the extent that the terms “including”, “includes”, “having”, “has”, “with”, or variants thereof are used in either the detailed description and / or the claims, such terms are intended to be inclusive in a manner similar to the term “comprising.” In some embodiments, the term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, “about” can mean within 1 or more than 1 standard deviation, per the practice in the given value. The term “subject” as used herein refers to any mammal. A subject therefore refers to, for example, mice, rats, dogs, cats, horses, cows, pigs, guinea pigs, rats, humans, monkeys, and the like. When 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), feline (e.g., a cat), equine (e.g., a horse), ovine, bovine, porcine, caprine, primate, e.g., a simian (e.g., a monkey (e.g., marmoset, baboon), or an ape (e.g., a gorilla, chimpanzee, orangutan, or 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 non-human mammal, especially mammals that are conventionally used as models for demonstrating therapeutic efficacy in humans (e.g., murine, lapine, porcine, canine, or primate animals) may be employed. In some embodiments, the term “therapeutically effective amount” refers to an amount of a polypeptide or composition effective to “treat” a disease, condition or disorder in a subject. In some cases, therapeutically effective amount of the polypeptide or composition reduces the severity of symptoms of the disease, condition or disorder. In some instances, the disease, condition or disorder comprises a defect in an organ or tissue. In some embodiments, “affinity” refers to the strength of the sum total of non-covalent interactions between a P-TCP binding sequence (or a chimeric polypeptide or polypeptide comprising a P-TCP binding sequence) and its binding partner (e.g., P-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®). Percent (%) sequence identity with respect to a reference polypeptide sequence is the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are known for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Appropriate parameters for aligning sequences are able to be determined, including algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For purposes herein, however, % amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc., and the source code has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc., South San Francisco, Calif., or may be compiled from the source code. The ALIGN-2 program should be compiled for use on a UNIX operating system, including digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary. In situations where ALIGN-2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the 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 will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. Unless specifically stated otherwise, all % amino acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program. Each of the embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible. A number of embodiments of the disclosure have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the disclosure. Additionally, while specific formulations for the inks are described, variations of the specific quantities of each ink ingredient are possible. Accordingly, other embodiments are within the scope of the following claims. EXAMPLES Example 1: Therapeutic Agent A chimeric polypeptide comprising a BMP therapeutic peptide connected to five betatricalcium phosphate binding peptides was expressed and purified using standard expression and purification methods. The chimeric polypeptide is referred to as tBMP-2 and has the following sequence: MPIGSLLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTH HKPWTASGAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTGQAKHKQRKRLKSSC KRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNS KIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR (SEQ ID NO: 434). Example 2: Device Manufacture A scaffold comprising beta-tricalcium phosphate was combined with the tBMP-2 therapeutic agent of Example 1 to create a device. Briefly, the scaffold was combined with tBMP- 2 in a binding solution and unbound tBMP-2 was washed off the scaffold. The resulting device comprised the scaffold with bound tBMP-2. The device was inserted into an interbody cage. Example 3: In Vivo Assessment of Interbody Fusion A device of Example 2 was tested in an animal model to demonstrate bone regeneration. A total of 64 sheep received a single level lumbar interbody fusion procedure through a lateral approach. Interbody fusion devices were filled with graft material (iliac crest bone graft or tBMP-2 at 0.8 or 2.0 mg / cc) prior to implantation. After implantation of the interbody device, bilateral posterior rod and pedicle screw instrumentation was implanted to stabilize the spine. PEEK interbody fusion devices (17mm x 10 mm x 6mm) were used in the main study cohort. Animals were sacrificed at 8, 16 and 26 weeks (N=6 per treatment per timepoint). A second cohort that received the same size titanium interbody fusion devices was sacrificed at 26 weeks only (N=3 per treatment). In life assessments included CT scans taken post-operatively and every four weeks through the 20- week time point. Graft preparation and surgical procedures are shown in FIG. 20. Blood was collected prior to implantation and at 8-, 16- and 26-weeks post implantation to assess hematological and biochemical parameters. At sacrifice, a final CT scan was performed, along with a comprehensive necropsy and organ and tissue sample collection for histopathology. Spinal segments were explanted and assessed by manual palpation, mCT imaging, mechanical testing and histological analysis of bone healing performance and local tissue effects consistent with ISO 10993-6. There was no evidence of systemic toxicity in any group, as determined by the clinical pathology (blood biochemistry and hematology) and gross morphology of the tissues at necropsy. Similarly, the local cell and tissue responses, based on ISO 10993-6, did not reveal any adverse reactions to the tBMP-2 bone graft. All animals were assessed as fused by manual palpation at 26 weeks. At 16-weeks, one animal in the ICBG group was assessed as not fused. At 8-weeks, two animals from the ICBG group and one each from the Low and High concentration tBMP-2 groups were not fused. Assessment of fusion based on CT scans showed increasing fusion scores over time as demonstrated in FIG. 3 and FIG. 4. The only statistical difference was greater fusion in animals treated with the Low Concentration tBMP-2 compared to ICBG at the 8-week timepoint. Fusion scores at 26 weeks were 3.8, 4 and 3.9 for Low Concentration tBMP-2, High Concentration tBMP-2 and ICBG, respectively. The radiographic fusion scores for Titanium interbody fusion devices were higher than PEEK for all graft materials only at the 4-week time point, likely due to beam hardening caused by the metal cage. An improvement in range of motion testing at 8 and 16 weeks was observed with tBMP-2, which was supported by the mCT and the histological data. Similarly, histology at 8 weeks demonstrated robust new bone formation for Low and High Dose tBMP-2 compared to ICBG, FIG. 5, while differences between groups were noted to lessen with time. Both dose levels of tBMP-2 facilitated fusion with a normal bone healing / remodeling response. Titanium and PEEK groups performed in a similar manner apart from the ability to confidently evaluate the fusions based on imaging. 26-week histology was assessed, and the bridging of bone is demonstrated in FIG. 6. FIG. 7A demonstrates 26-week histology showing marrow formation, bone formation, osteoblasts, and graft fibers in ICBG and FIG. 7B demonstrates the same measures in the tBMP-2 group. This study demonstrates preclinical safety and efficacy of tBMP-2 grafts at two concentrations in a clinically relevant large animal model. Performance and safety of tBMP-2 was comparable to or better than the gold standard, ICBG, in all measures. The tBMP-2 performed better than ICBG for measures of spinal fusion at the early time points, indicative of faster bone growth following surgery. This study enables the selection tBMP-2 formulations for pilot human clinical investigation. tBMP-2 bone grafts with specific carrier binding of tBMP-2 shows promise for precise localization of bone formation and consistent spinal fusion. With the protein specifically bound to the carrier matrix, tBMP-2 bone grafts represents an advancement over current technologies by simplifying product preparation and limiting the risk of pain and adverse events associated with off target response. Example 4: Advanced Bone Graft Feasibility Study -Spinal Fusion The purpose of the clinical study is to assess the safety and effectiveness of a tBMP-2 bone graft as a replacement for the autograft standard of care bone graft within the interbody cage, as well as identify the tBMP-2 dose to be investigated in a future pivotal study. This study is a prospective, blinded, controlled, dose-randomized, multicenter, investigational study to evaluate the safety and effectiveness of the t-BMP-2 bone graft in singlelevel spinal fusion procedures (e.g., ALIF, LLIF, OLIF, or TLIF procedures) for the treatment of symptomatic degenerative diseases of the lumbosacral spine. Additional conditions include degenerative disc disease, degenerative spondylolisthesis, spinal stenosis, spine disease, lumbar radiculopathy, lumbar spinal stenosis, lumbar disc herniation, lumbar disc disease, lumbar spine degeneration, and lumbar spondylolisthesis. Patients undergoing elective single-level, single interbody cage TLIF, ALIF, LLIF, or OLIF, who have had at least 6 months of conservative care, met the inclusion criteria and none of the exclusion criteria, and sign the patient informed consent are screened for enrollment and treated consistent with current surgical standard of care except that the autograft bone graft component within the interbody cage will be packed with tBMP-2 bone grafts. Patients are randomized to receive tBMP-2 at one of two available concentrations (0.8 mg / cc or 2 mg / cc) with - 25-26 patients in each group, or the control group consisting of another -25-26 patients for a total of-75-80 patients. Standard lottery randomization is used with equal weight in each of the three groups. The investigational group uses the randomized concentration of tBMP-2 within the interbody cage and placement of autograft anterior (or laterally within the disc space) to the cage if desired by the investigator. Control subjects have autograft harvested from the local site and utilized both inside and anterior (or lateral) to the interbody cage with the option of banked mineralized frozen allograft to supplement if there is not enough local autograft available. Arm 1 Experimental: Low Dose composition (0.8 mg / cc tBMP-2 / scaffold) Participants will receive a Lumbar Interbody Fusion (ALIF, LLIF, OLIF, or TLIF) with Low Dose inside the interbody fusion cage with the availability of having local autograft placed anterior / lateral to the cage within the disc space. The composition is hydrated at the time of surgery with saline and placed into the interbody fusion cage. Arm 2 Experimental: High Dose composition (2 mg / cc tBMP-2 / scaffold) Participants will receive a Lumbar Interbody Fusion (ALIF, LLIF, OLIF, or TLIF) with High Dose inside the interbody fusion cage with the availability of having local autograft placed anterior / lateral to the cage within the disc space. The composition is hydrated at the time of surgery with saline and placed into the interbody fusion cage. Arm 3 Experimental: Control (Standard of Care - Autograft / Mineralized Autograft) Patients will follow standard of care Lumbar Interbody Fusion (ALIF, LLIF, OLIF, or TLIF) in which local autograft will be placed inside the interbody fusion cage with the availability of mineralized, frozen, banked, allograft to be placed anterior / lateral to the cage. For ALIF and LLIF, if local bone is not available, commercially available allograft products comprising only demineralized bone matrix and / or mineralized allograft chips, without any other components, will be utilized inside the interbody cage. No grafting material will be placed outside of the cage. For TLIF, Arm 3 will receive autograft harvested from local site and utilize both inside and outside the interbody cage with the option of banked mineralized allograft to supplement if there is not enough local autograft available. Outcome Measures Primary Outcome Measures : Rate of Subjects requiring Secondary Surgical Interventions within 24 months post-op. [ Time Frame: up to 24 months post op ] No secondary surgical interventions, due to fusion failure or non- union, including reoperation, supplemental fixation, removal, or revision of the Investigational Device within the study follow up timeframe of 24 months. Neurological Status assessed via Motor, Sensory, and Reflex physical exams with outcome measures of "normal", "abnormal" or "unknown". Success defined as maintenance or improvement compared to baseline assessment. [ Time Frame: Baseline compared to 24 months post op ] • Maintenance or improvement in neurological status affected by the index level at 24 months post-op as compared to baseline measures, as adjudicated by the Medical Monitor. Oswestry Disability Index - Measured on a scale of 0-100 points, 0 being least physically impaired for day to day activities and 100 being extremely difficult or impossible to perform day to day activities. [ Time Frame: Baseline compared to 24 months post op ] • Oswestry Disability Index will be compared at 24 months post-op to baseline measures based on a scale of 0-100 points (0 = not physically impaired for day to day activities; 100= severe impairment of day to day activities) Adjacent level progression of pathology will be assessed for any failures of this criteria and adjudicated by the Medical Monitor. Numeric Pain Rating Scale - Pain scale measured on a scale from 0 to 10 (0=no pain; 10 = pain as bad as it can be) compared at 24 months post op to baseline assessment. [ Time Frame: Baseline compared to 24 months post op ] • Assessment of the Numeric Pain Rating Scale (NPRS) for back and / or leg pain and defined on a scale of 0 to 10 (0 =no pain; 10 = pain as bad as it can be) Pain scores will be compared at 24 months to baseline values. Adjacent level progression of pathology will be assessed for any failures of this criteria and adjudicated by the Medical Monitor. Radiographic Fusion Assessment - assessed by CT at 6-, 12- and 24-months post op as bridging bone from endplate to endplate. [ Time Frame: Assessed at 24 months post op ] • Radiographic fusion as defined below within 24 months post-op: Presence of Bridging Bone (CT) in at least one of the following locations: Interbody space; or anterior, lateral, or posterior to interbody fusion device. Bridging bone is defined as continuous evidence of bridging bone, whether it be a thin line, or a thicker column of bone; AND No evidence of motion as defined by less than 3mm translational motion and less than 5° in angular motion at each treated level. No radiological evidence of bridging bone in adjacent levels. Secondary Outcome Measures : PROMIS short form, validated, quality of life questionnaire to assess subjects overall mental and general health through a series of 12 questions regarding depression, anxiety, and general health. [ Time Frame: 24 months post op ] • Assess the subject's health related overall quality of life through the PROMIS Short Form Questionnaire. Assessment for Immunogenic effects (e.g., anti BMP-2) caused by tBMP2 antibodies as detected in subject's blood serum through antibody assays. [ Time Frame: Pre-op to 24 months (if applicable) ] Assessment for Immunogenic effects (e.g., anti BMP-2) through BMP2 antibody and neutralizing antibody assays. Disc height assessment at the operative level as determined by plain Xray radiographs at each study timepoint. [ Time Frame: Pre-op, 6 weeks, 3 months, 6 months, 12 months, 24 months ] Disc height assessment at the operative level through radiographic analysis Inclusion Criteria: Male or Female age 18-80 (inclusive) at time of signing informed consent and skeletally mature (as determined by physician's assessment of AP lumbar Xray utilizing the Risser Classification method of the iliac crest growth plates) (See addendum 1 for a definitive reference on skeletal age); Subject is planning to undergo a unilateral, single-level, single interbody cage, ALIF / LLIF / TLIF procedure (from L2-S1 with posterior supplemental fixation) with a primary diagnosis of symptomatic lumbar degeneration including back and / or radicular pain with or without foraminal or recess stenosis confirmed by patient history, physical examinations, and radiographic imaging (Xray, CT, MRI) with no more than Grade 2 Spondylolisthesis with one or more of the following factors: Instability as defined by > / -3mm translation or > / -5° angulation; Osteophyte formation of facet joints or vertebral endplates; Decreased disc height, on average by >2mm, but dependent upon the spinal level; Scarring / thickening of ligamentum flavum, annulus fibrosis, or facet joint capsule; Herniated nucleus pulposus; facet joint degeneration / changes; and / or Vacuum phenomenon. Preoperative ODI score >35 at pre-op / baseline; Preoperative back and / or leg pain score of >4 (out of 10); Failed >6 months non-operative / conservative treatment (e.g., physical therapy, bracing, traction, medication, TENS, and / or spinal injections; Is willing and able to be present for routine follow up visits, comply with postoperative management program, and is able to understand and sign the informed consent form. Exclusion Criteria: Patient requires spinal fusion surgical procedure (ALIF / LLIF / TLIF) at more than one level (nonfusion surgery at the non-index levels, including discectomy and / or single level foraminotomy or laminectomy, is allowed) Prior spinal fusion surgical procedure at the involved or adjacent spinal levels, or non-fusion stabilizing surgeries, e.g., interlaminar devices, dynamic stabilization, or disc replacements. (Prior non-fusion surgery at the target levels, including discectomy and / or single level foraminotomy or laminectomy, is allowed.) Greater than Grade 2 Spondylolisthesis; Planned use of an internal or external bone growth stimulator; Osteoporosis to a degree that spinal instrumentation is contraindicated or a history of a traumatic vertebral fracture. All patients complete SCORE / MORE to assess the need for DEXA scan. If DEXA is required, patients with a T score < / - 2.5 will be excluded. A prior DEXA can be used if performed within 9 months pre-op; Morbidly obese, as defined by a Body Mass Index (BMI) >40; Overt or active bacterial infection, either local or systemic; The subject uses, or has used within 30 days of surgery, tobacco or nicotine or is prescribed steroids such as cortisone; (subjects will undergo a nicotine test during screening procedures utilizing a standard commercial cotinine urine dip test; Example: Easy@Home Nicotine Cotinine Urine Panel Dip Test Strips Kit- Sensitive (healthcare-manager.com) Comorbidities precluding subject from being a surgical candidate; Systemic disease including Lupus disease, Reiter's disease, Rheumatoid disease, AIDS, HIV, hepatitis, or autoimmune disease that requires immunosuppressive therapy, including biologies, for systemic inflammation. History of malignancy, radiotherapy, or chemotherapy for any malignancy within the last 5 years. History of malignancy may include multiple exostoses syndrome ((also known as multiple osteochondromas syndrome), an inherited condition associated with bumps of cartilage on the bones, has been associated with an increased risk of chondrosarcoma); individuals who have undergone any transplant surgery and are on immunosuppressant therapy. Has history of any endocrine or metabolic disorder known to affect osteogenesis (e.g.: Paget's disease, renal osteodystrophy, Ehler-Danlos syndrome, or osteogenesis imperfecta); Has insulin dependent diabetes and an A1C > 7.0; History of exposure to any recombinant proteins or peptides used for bone formation (i.e., Infuse Bone Graft, AUGMENT Bone Graft, GEM21S, i-FACTOR Peptide Enhanced Bone Graft, or PepGen P-15 Synthetic Bone Graft); Hypersensitivity or allergy to any components of the study treatments including, but not limited to, bone morphogenetic proteins (BMPs); tricalcium phosphate (TCP); PLGA polymer; and / or instrumentation materials (titanium, titanium alloy, PEEK). History of any allergy resulting in anaphylaxis; Is a prisoner; Is mentally incompetent. If questionable, obtain psychiatric consult; History of substance abuse (substance abuse defined by DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) code. Criteria for substance abuse defined in Addendum 2. Involved in litigation for spine injury or worker's compensation case; Treatment with an investigational therapy (drug, device, and / or biologic) within 120 days prior to implantation surgery, or such treatment is planned during the 24-month period following implantation of the study treatment; prior or planned use of rhBMP-2. Pregnant (or interested in becoming pregnant in the next 24 months) or nursing. Any condition that would interfere with the subject's ability to comply with study instructions or prohibit MRI / CT / Radiographic assessments that might confound the interpretation of the study or put the subject at risk. Patients with any positive pregnancy test. Tests will be administered at the surgical center prior to surgery. Patient currently taking any drug known to interfere with bone / soft tissue healing. See "Medication Protocol" section of the Investigator's Brochure. Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements. Example 5. Patient Report from Phase I / II Clinical Trial in Spinal Fusion Patients A patient with debilitating pain radiating from their back to their ankle was enrolled in a randomized trial involving 78 patients, in which the treatment arms comprise a spinal fusion surgery followed by intervertebral implantation of a tBMP-2 / scaffold device. Despite not knowing which option he received, the study’s first patient says participating in the clinical trial gave new hope, as he experienced a significant decrease in pain following surgery. The patient reported that the previously debilitating leg pain was gone immediately after the surgery, and reported positive X-rays and blood tests on follow-up. Example 6. Clinical Trial in ACDF Patients Study Design Anterior Cervical Discectomy and Fusion (ACDF) is a surgical treatment option for symptomatic degenerative cervical disk disease patients who fail conservative treatment. In this study, subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Following ACDF surgery, an interbody cage packed with tBMP-2 / scaffold and hydrated with saline is implanted in the intervertebral space between the fused vertebrae. As a control comparator, following ACDF surgery, control patients are implanted with an interbody cage packed with local bone graft or allograft bone material. Inclusion Criteria Age between 18 and 65; Radiographically determined discogenic origin to include at least one of the following characteristics: degenerated / dark disc on MRI, decreased disc height compared to adjacent levels on radiographic film, CT, or MRI and disc herniation on CT or MRI; Radicular symptoms by history and physical exam to include at least the following characteristics: Arm / shoulder pain, decreased flexes, decreased strength and abnormal sensation; Pain level arm / shoulder >4 on 0-10 VAS; Pain level neck >4 on 0-10 VAS; Neck disability Index >30; Involved discs between C3 and C7; Undergoing anterior cervical fusion at a single level; Failed to gain adequate relief from non-operative treatment; Able and willing to give consent to participate in study; Understand and read English at elementary level. Exclusion Criteria Systemic infection such as AIDS, HIV, and active hepatitis; Significant metabolic disease that in the surgeon's opinion might compromise bone growth such as osteoporosis or osteomalacia; Taking medication for the prevention of osteoporosis; Circulatory, cardiac, or pulmonary problems that could cause excessive surgical risk; Active malignancy, Nondiscogenic source of symptoms (e.g., tumor, etc.); Multiple level symptomatic degenerative disc disease; Previous cervical fusion; Previous cervical decompression at the same level, Acute cervical trauma or instability (i.e., subluxation > 3 mm on flexion / extension radiographic film); Undergoing treatment for tumor or bony traumatic injury to the cervical spine, Rheumatoid disease of the cervical spine, Myelopathy; Pregnant or planning to become pregnant in the next 2 years, Posterior cervical spine procedure scheduled; More than one level to be operated; Has a history of substance abuse (recreational drugs, alcohol); Is a prisoner; Is currently involved in a study of another investigational product for similar purpose; Has a disease process that would preclude accurate evaluation (e.g., neuromuscular disease, significant psychiatric disease). Primary Outcome Measures (i) Radiologic Fusion after 12 months: Successful fusion is based on roentgenographic examination showing evidence of bridging trabecular bone between the involved motion segments, translational motion <3mm, and angular motion <5 degrees. If there is a lack of evidence of fusion on 12 month plain x-ray examination, a CT-scan is performed and final determination of the fusion status is made using the CT reading. The criteria for fusion on CT scans are: trabecular bone formation patterns within the intervertebral disc space and bridging bone formation that crosses the interspace. (ii) Change in of the Overall Neck Disability Index (NDI) Score from Baseline after 12 months: The NDI consists of ten items addressing functional activities (personal care, lifting, reading, work, driving, sleeping, recreational activities), pain intensity, concentration and headache. For each item, there are six potential responses, describing increasing degrees of disability (no disability :;= 0 to total disability :=: 5). An overall NDI score, out of 100, is calculated by adding up the scores for each item and multiplying by two. A higher NDI score indicates greater disability. (iii) Neurologic Success: The neurological endpoint is a binary variable. Neurologic success is assessed in the motor, sensory and reflex domains specific for the cervical spine as follows: maintenance or improvement of motor function in the elbow flexors (i.e. biceps muscle), elbow extensors (i.e. triceps muscle) and wrist extensors of both arms; maintenance or improvement of sensory functi on of both arms, maintenance or improvement of reflexes of both arms as measured at biceps tendon, triceps tendon and brachioradialis (supinator) reflex AND absence of Babinski reflex (if not present prior to surgery). Worsening of neurological status (neurological failure) is defined as a permanent decline in the subject’s neurological status based on adjudication of accumulated neurological data by an independent blinded evaluator. (iv) Complications: Any adverse events within 12 months of surgery. Secondary' Outcome Measures (i) Mean Change in Pain at Neck Visual Analog Scale (VAS): The pain VAS is a continuous scale upon which the subject indicates their pain level ranging from "No pain at all" (0) to "Worst imaginable pain" (10). The change in pain is calculated by subtracting the 12 month score from the baseline score. (ii) Mean Change at Pain at Arm and Shoulder Visual Analog Scale (VAS): The pain VAS is a continuous scale upon which the subject indicates their pain level ranging from "No pain at all” (0) to "Worst imaginable pain" (10). The change in pain is calculated by subtracting the 12 month score from the baseline score. (iii) Success Rates Measured by Aggregated Modified Odom's Criteria: Subjects selected one of four categories: Excellent (Improvement Greater than or Equal to 80%, Deterioration Less than 10%), Good (Improvement Greater than or Equal to 70%, Deterioration Less than 15%), Fair (Improvement Greater than or Equal to 50%, Deterioration Less than 20%) or Poor (Improvement Less than 50%, Deterioration Greater than 20%). (iv) Mean Change in the Short Form 36 v2 (SF-36v2) Physical Composite Score (PCS): The SF-36 v2 (Medical Outcomes Trust, Boston, MA) is a multipurpose, patient-reported short-form health survey with 36 questions available in several languages. It yields two composite scores: one for physical health (Physical Composite Score - PCS) and one for mental health (Mental Composite Score - MCS) that are comprised of eight domains. The following domains make up the PCS: physical functioning, role-physical, bodily pain, general health. The PCS ranges from a score of 0 (lowest possible level of functioning) to a score of 100 (highest possible level of functioning). (v) Mean Change in the Short Form 36 v2 (SF-36v2) Mental Health Composite Score (MCS): The SF-36 v2 (Medical Outcomes Trust, Boston, MA) is a multipurpose, patient-reported short-form health survey with 36 questions available in several languages. It yields two composite scores: one for physical health (Physical Composite Score - PCS) and one for mental health (Mental Composite Score - MCS) that are comprised of eight domains. The following domains make up the MCS: vitality, social functioning, role-emotional, mental health. The MCS ranges from a score of 0 (lowest possible level of functioning) to a score of 100 (highest possible level of functioning), (vi) Kyphosis, evaluated in degrees, 12 months after surgery. Example 7. Rabbit Posterolateral Fusion Dosing Study A device of Example 2 was tested in a rabbit posterolateral fusion model. Posterolateral fusion involves the placement of bone graft along the posterior aspects of the spine spanning decorticated transverse processes. The rabbit model is uninstrumented, i.e., there is no posterior rod and screw instrumentation. The rabbit posterolateral fusion model is a validated animal model that is the subject of an ASTM standard guide (Boden 1995, ASTM F3207-17). The model is commonly used to assess the potential efficacy of bone grafting materials. Twelve male, skeletally mature, New Zealand White rabbits underwent single level posterolateral fusion at L5-L6 with the device as the bone grafting material. No iliac crest bone graft was used. Treatment groups differ in concentration of BMP-2 per gram of carrier and mass of carrier implanted. About 3cc of graft material on either side of the spine was implanted. The groups were as follows: Group 1: 6 mg BMP-2 / g scaffold; 1 g device per side of spine; 6 mg BMP-2 per side of spine, at a concentration of BMp-2 of 2.0 mg / cc; Group 2: 8.6 mg BMP-2 / g scaffold; 0.7 g device per side of spine; 6 mg BMP-2 per side of spine, at a concentration of BMp-2 of 2.0 mg / cc; Group 3:15 mg BMP-2 / g scaffold; 0.4 g device per side of spine; 6 mg BMP-2 per side of spine, at a concentration of BMp-2 of 2.0 mg / cc; and Group 4: 6 mg BMP-2 / g scaffold; 0.4 g device per side of spine; 2.4 mg BMP-2 per side of spine, at a concentration of BMp-2 of 2.0 mg / cc. The device was hydrated with peripheral blood drawn from the rabbit just prior to surgery. The volume used to hydrate the graft was proportional to the mass of the graft being implanted (2.5 mL / g). The transverse processes were decorticated, and the device was placed bilaterally such that it spanned the distance between the L5 and L6 transverse processes. Post-operative x-rays were taken to assess initial visualization of the implanted graft. Animals were euthanized at 8 weeks. Fusion was determined by manual palpation, x-ray, and pCT. All samples were processed and stained for decalcified histopathology and histomorphometric analysis. All animals tolerated the surgery well and recovered uneventfully. The location and shape of the implanted graft was visualized on post-operative x-rays for all treatment groups, with the higher density groups having greater radiopacity. At necropsy, the implant sites demonstrated normal healing. There were no apparent adverse effects such as inflammation or tissue necrosis. At 8 weeks, all spines were graded as fused based on manual palpation. Qualitatively, the size of the fusion masses correlated with the mass of the material implanted. Plain radiographs showed extension of the fusion masses cranially toward the L4-L5 spine segment in most animals. Comparison between post-op and 8-week x-rays showed that the extension of new bone formation corresponded to the initial placement of the graft material. The pCT images confirmed the results from manual palpation and plain x-ray, showing bridging bone bilaterally in all animals. The quality of bone in terms of maturity and structural development was similar between treatment groups, based on pCT. Histopathology showed no significant differences of new bone formation between the four implant groups. Regenerate bone contained incorporated polymer fibers, indicating that the new bone formation was limited to the implant mass. FIG. 8 shows representative sagittal reconstruction of microCT and H&E histology image from all treatment groups at 8 weeks showing normal bone bridging the transverse processes. Example 8. Sheep Lumbar Interbody Fusion Pilot Study A device of Example 2 was tested in a sheep lumbar interbody fusion model. The sheep model of lumbar interbody fusion is commonly used as a clinically relevant large animal model to support clinical investigations of human lumbar interbody fusion. While the size of the sheep disc space is smaller than human, the range of motion of the sheep lumbar spine is similar to humans, and the sheep disc space is suitable for implantation of interbody fusion devices loaded with bone grafting materials. In this study, a total of three sheep received lumbar interbody fusion at two consecutive levels using a modified TLIF surgical approach. The device was placed inside of an interbody fusion device (FIGS. 9A, 9B). The interbody fusion devices were PEEK cages (20 mm X 14 mm X 6mm) with an internal volume of ~0.5 cc. Each animal received the device at low (0.8 mg BMP-2 / cc defect) concentration in one level and the device at high (2.0 mg BMP-2 / cc defect) concentration in the adjacent level. Bilateral posterior rod and screw instrumentation was implanted after placement of the interbody devices. CTs scans were performed at 4, 8 and 12 weeks. Animals were sacrificed at 26 weeks and microCT scans were performed on explanted spine segments. Fusion was assessed based on microCT and manual palpation. MicroCT images were used to determine percent bone formation for comparison between groups. Histological evaluations were also performed on each specimen. This study demonstrates that both low and high concentrations of BMP2 were capable of inducing spinal fusion in the sheep interbody model.

Claims

1. A method of treating the spine in a subject in need thereof, the method comprising implanting a device in a cavity of the subject in a spinal procedure, wherein the device comprises a recombinant BMP-2 comprising a binding peptide, and a ceramic scaffold; and wherein the spinal procedure is a lumbar interbody fusion procedure selected from Transforaminal Lumbar Interbody Fusion (TLIF), Lateral Lumbar Interbody Fusion (LLIF), Posterior Lumbar Interbody Fusion (PLIF), Anterior Lumbar Interbody Fusion (ALIF), Oblique Lateral Interbody Fusion (OLIF), and Extreme Lateral Interbody Fusion (XLIF).

2. A method for treating the spine in a subject in need thereof, the method comprising implanting a device in a cavity of the subject in a spinal procedure, wherein the device comprises a recombinant BMP-2 comprising a binding peptide, and a ceramic scaffold; and wherein the spinal procedure is Interspinous Process Fusion (ILIF), Anterior Cervical Discectomy and Fusion (ACDF), Posterior Spinal Fusion (PSF), Posterolateral Spinal Fusion (PLF) facet fusion, interspinous fusion, Sacroiliac Joint Fusion, or Kyphoplasty.

3. A method for treating a condition of the spine in a subject in need thereof, the method comprising implanting a device in a cavity of the subject during a spinal procedure, wherein the device comprises a ceramic scaffold and a recombinant BMP-2 comprising a binding peptide; wherein the condition of the spine is degenerative disc disease, iatrogenic injury to the spine, congenital spinal condition or deformity, scoliosis, spondylolisthesis, spinal stenosis, fractured vertebra, trauma to the spine, infection of the spine, or tumor of the spine.

4. The method of claim 1 or claim 2, wherein the subject has a degenerative disc disease, iatrogenic injury to the spine, congenital spinal condition or deformity, scoliosis, spondylolisthesis, spinal stenosis, fractured vertebra, trauma to the spine, infection of the spine, or tumor of the spine.

5. The method of any one of claims 1-4, wherein the recombinant BMP-2 is non-covalently bonded to the ceramic scaffold.

6. The method of any one of claims 1-5, wherein the treating results in improved spinal stability, reduced back pain, increased mobility, or reduced deformation of the spine, or a combination of two or more thereof.

7. The method of any one of claims 1-6, wherein about 0.08 mg to about 8 mg BMP-2 / cc of the cavity is implanted in the subject, and / or wherein about 0.08 mg to about 8 mg BMP-2 / cc of the ceramic scaffold is implanted in the subject.

8. The method of any one of claims 1-7, wherein about 0.4 mg to about 4 mg BMP-2 / cc of the cavity is implanted in the subject, and / or wherein about 0.4 mg to about 4 mg BMP-2 / cc of the ceramic scaffold is implanted in the subject.

9. The method of any one of claims 1-8, wherein about 0.8 mg to about 2 mg BMP-2 / cc of the cavity is implanted in the subject, and / or wherein about 0.8 mg to about 2 mg BMP-2 / cc of the ceramic scaffold is implanted in the subject.

10. The method of any one of claims 1-9, wherein about 0.8 mg BMP-2 / cc of the cavity is implanted in the subject, and / or wherein about 0.8 mg BMP-2 / cc of the ceramic scaffold is implanted in the subject.

11. The method of any one of claims 1-9, wherein about 2 mg BMP-2 / cc of the cavity is implanted in the subject, and / or wherein about 2 mg BMP-2 / cc of the ceramic scaffold is implanted in the subject.

12. The method of any one of claims 1-11, wherein the ceramic scaffold comprises tricalcium phosphate, beta tricalcium phosphate, alpha tricalcium phosphate, or a combination thereof.

13. The method of any one of claims 1-12, wherein the binding peptide comprises one or more peptides of Table 1 or Table 2.

14. The method of any one of claims 1-12, wherein the recombinant BMP-2 comprises SEQ ID NO: 434 or 435, or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 434 or 435.

15. The method of any one of claims 1-14, wherein the device further comprises an interbody cage, anterior cage, posterior cage, expandable cage, corpectomy cage, biodegradable cage, artificial disc, or a grafted cage.

16. The method of claim 15, wherein the interbody cage comprises titanium, polyetheretherketone (PEEK), polyetherketoneketone (PEKK), carbon fiber, grafted or synthetic bone, or any combination thereof.

17. The method of any one of claims 1-16, wherein the subject has the presence of bridging bone, optionally as assessed by CT (computed tomography).

18. The method of any one of claims 2-16, wherein the spinal procedure is a non-interbody procedure.

19. The method of any one of claims 1-18, wherein the subject does not require a secondary surgical intervention within 24 months of the implanting.

20. The method of any one of claims 1-19, wherein after implanting, the neurological status of the subject is maintained or improved.

21. The method of any one of claims 1-20, wherein the subject’s Oswestry Disability Index is decreased after the implanting.

22. The method of any one of claims 1-21, wherein the subject’s pain is reduced after the implanting, wherein the pain is optionally reduced within 24 months after implanting as compared to before the implanting.

23. The method of any one of claims 1-22, wherein the subject has bone fusion as assessed by radiographic fusion assessment, optionally as assessed by CT (computed tomography).

Images