Bioprinted soft tissue-reinforced scaffolds

Abstract

The present disclosure encompasses systems, compositions, and methods for in vivo use, including for the reinforcement of soft tissue in an individual. The systems, compositions, and methods may utilize three-dimensionally printed scaffolds that include at least a polymer scaffold and an extracellular matrix component, including those contained on the scaffold. The polymer scaffold may include a particular unit cell structure in a particular design and pattern of alternating configurations of unit cell structures.

Description

[Technical Field]

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 376,658, filed September 22, 2022, which is incorporated herein by reference in its entirety. [Background technology]

[0002] The present disclosure relates at least to the fields of chemistry, biology, biocompatible structures, wound care, and medicine, including compositions and materials used to form bio-scaffold structures that can be utilized in individuals, such as for the reinforcement and / or regeneration of soft tissue. There are a variety of materials available to provide tissue reinforcement and / or fill in excised tissue to reconstruct the original shape of soft tissue. Summary of the Invention [Means for solving the problem]

[0003] Embodiments of the present disclosure include systems, methods, and compositions related to soft tissue regeneration, reinforcement, and / or repair. In various embodiments, the present disclosure relates to specific structures for soft tissue regeneration, reinforcement, and / or repair, which structures provide structural and therapeutic elements to facilitate such activities. In certain embodiments, the present disclosure relates to scaffolds configured to provide mechanical support to soft tissue while also delivering biomolecules that enhance at least soft tissue regeneration and repair, and in certain cases, the scaffolds elicit minimal or no immunogenic response in recipient individuals. In certain embodiments, the present disclosure provides scaffold compositions fabricated from materials that minimize an immunogenic response in the host while providing a structural framework for tissue regrowth. In embodiments, the scaffold provides dual benefit to the recipient individual by providing (1) a physical structure composed of a defined unit cell structure to provide support, but further composed of a suitable polymer to impart adequate strength and flexibility for in vivo use, and (2) a therapeutic component as a coating (and / or within the physical structure) to allow enhanced cell and / or tissue growth and / or infiltration at the soft tissue site in need. In some embodiments, the scaffold acts as a delivery component to deliver the therapeutic component. In certain embodiments, the scaffold utilizes a specific pattern to replicate native mechanical tissue properties that other synthetic scaffolds cannot. In embodiments, three-dimensional (3D) printing generates the scaffold.

[0004] Certain embodiments provide scaffolds comprised of one or more biodegradable polymers and one or more extracellular matrix materials, the scaffolds being comprised of rows of repeating unit cell structures or unit patterns of a particular design. In embodiments, the unit cell structure or unit pattern design comprises particular shapes, including shapes that are generally capital "I" structures. In certain embodiments, the scaffolds comprise rows of capital "I" unit cell structures or unit patterns in a vertically alternating configuration.

[0005] Embodiments of the present disclosure provide an artificial support structure comprising one or more biodegradable polymers and one or more extracellular matrix materials, further comprising a plurality of unit patterns, each comprising a plurality of filaments arranged continuously, symmetrically, and regularly thereon, each unit pattern constructed with closed-shaped edges, thus forming pores therein, and the unit patterns connected, thus having intersections with each other, the number of intersections being equal to the number of edges passing through the intersections. In certain embodiments, the one or more extracellular matrix materials comprise collagen I. In certain embodiments, at least one unit pattern has a diameter of about 200 microns to about 3.5 mm. In certain aspects, at least one unit pattern has a diameter of about 1.5 mm to about 3 mm or about 1.782 mm to about 2.97 mm. In certain embodiments, the biodegradable polymer material may further comprise one or more extracellular matrix materials, such as collagen I.

[0006] In certain embodiments, the plurality of connected unit patterns forms a substantially planar sheet. The plurality of connected unit patterns can, in certain aspects, form a three-dimensional macrostructure, and the artificial support structure, in various embodiments, has a thickness of about 0.5 mm to about 1.5 mm, about 0.7 mm to about 1.3 mm, or about 0.9 mm to about 1.1 mm. In some cases, the artificial support structure comprises, consists of, or consists essentially of 1 to 5 layers, and the layers can have a thickness of about 0.10 mm to about 0.3 mm, about 0.15 mm to about 0.25 mm, or about 0.18 mm to about 0.22 mm. In some embodiments, one or more filaments in the plurality of filaments have a diameter of less than about 550, 500, or 400 microns.

[0007] In some embodiments, four unit patterns are connected to one another with four intersections and four edges that pass through or intersect the four intersections, and the space enclosed by the four unit patterns has the same or similar shape as each of the unit patterns. In certain embodiments, each unit pattern is the capital letter "I" of the English alphabet, and in some embodiments, the short edges of the closed shape of each unit pattern have the same length as each other, and the long edges of the closed shape of each unit pattern have the same length as each other, and the space enclosed by the four unit patterns has the same shape as each of the unit patterns. In certain cases, the ratio of the lengths of the short edges to the long edges of the closed shape is 1:3.

[0008] In various embodiments, the artificial support structure has an ultimate tensile strength of about 4 MPa to about 5 MPa, about 4.05 MPa to about 4.7 MPa, or about 4.12 MPa to about 4.50 MPa. In some embodiments, the artificial support structure has a modulus of elasticity of about 2.8 MPa to about 4.2 MPa, about 3.00 MPa to about 4.10 MPa, or about 3.06 MPa to about 4.00 MPa. In specific embodiments, the artificial support structure has a suture retention strength of about 20 N to about 26 N, about 21 N to about 25 N, or about 22.03 N to about 24.27 N. In specific embodiments, the artificial support structure has a burst strength of about 140 N to about 170 N, about 145 N to about 163 N, or about 147.14 N to about 161.26 N. In various embodiments, the artificial support structure has a tear resistance of about 18N to about 26N, about 19N to about 25N, or about 19.87N to about 24.92N.

[0009] Embodiments of the present disclosure include an artificial support structure comprising one or more biodegradable polymers and one or more extracellular matrix materials (such as collagen I), wherein the support structure further comprises a plurality of unit patterns, each comprising a plurality of filaments arranged to form symmetrical rows or columns, each unit pattern constructed with a closed edge, thus forming pores therein, and the columns or columns in which the plurality of unit patterns are repeated have Eulerian paths. In certain embodiments, at least one unit pattern has a diameter of about 200 microns to about 3.5 mm, about 1.5 mm to about 3 mm, or about 1.782 mm to about 2.97 mm. In certain embodiments, the biodegradable polymer material further comprises one or more extracellular matrix materials, such as collagen I.

[0010] In certain embodiments, the plurality of connected unit patterns form a substantially planar sheet, e.g., the plurality of connected unit patterns form a three-dimensional macrostructure. In certain aspects, the artificial support structure has a thickness of about 0.5 mm to about 1.5 mm, about 0.7 mm to about 1.3 mm, or about 0.9 mm to about 1.1 mm, in various embodiments. In some cases, the artificial support structure comprises 1 to 5 layers, and the layers may have a thickness of about 0.10 mm to about 0.3 mm, about 0.15 mm to about 0.25 mm, or about 0.18 mm to about 0.22 mm. In some embodiments, one or more filaments in the plurality of filaments have a diameter of less than about 550, 500, or 400 microns.

[0011] In various embodiments, columns or rows in which multiple unit patterns are repeatedly arranged are connected so that the multiple unit patterns have intersections with the multiple unit patterns in adjacent columns or rows. In certain embodiments, the number of intersections between the multiple unit patterns is the same as the number of edges passing through the intersections. In a specific case, four adjacent unit patterns are connected so that they have four intersections with each other and four edges passing through the four intersections, and the space enclosed by the four unit patterns has the same or similar shape as each unit pattern. In a specific embodiment, each unit pattern is the capital letter "I" of the English alphabet. In various embodiments, the short edges of the closed shape of each unit pattern have the same length as each other, and the long edges of the closed shape have the same length as each other, and the space enclosed by the four unit patterns has the same shape as each unit pattern. In a specific case, the ratio of the lengths of the short edges to the long edges in the closed shape is 1:3. In a specific embodiment, the ratio of the lengths of the short edges to the long edges in the closed shape is 1:3. In various embodiments, the plurality of unit patterns in a row or column are repeatedly arranged such that the plurality of unit patterns are at an angle of 45° or 135° relative to the row or column, and in some embodiments, a portion of the edges of the plurality of unit patterns are regularly arranged to form the edge of the prosthetic support.

[0012] In various embodiments, the artificial support structure has an ultimate tensile strength of about 4 MPa to about 5 MPa, about 4.05 MPa to about 4.7 MPa, or about 4.12 MPa to about 4.50 MPa. In some embodiments, the artificial support structure has a modulus of elasticity of about 2.8 MPa to about 4.2 MPa, about 3.00 MPa to about 4.10 MPa, or about 3.06 MPa to about 4.00 MPa. In specific embodiments, the artificial support structure has a suture retention strength of about 20 N to about 26 N, about 21 N to about 25 N, or about 22.03 N to about 24.27 N. In specific embodiments, the artificial support structure has a burst strength of about 140 N to about 170 N, about 145 N to about 163 N, or about 147.14 N to about 161.26 N. In various embodiments, the artificial support structure has a tear resistance of about 18N to about 26N, about 19N to about 25N, or about 19.87N to about 24.92N.

[0013] Embodiments of the present disclosure include a scaffold comprising a patterned polymeric substrate having thereon a coating of one or more extracellular matrix (ECM) materials, the pattern of the polymeric substrate comprising a series of adjacent rows of unit cell structures, each generally shaped like the letter "I," the unit cell structures aligned within the rows of the patterned polymeric substrate in a perpendicularly alternating pattern of unit cell structures. In certain embodiments, the series of unit cell structures is further defined as comprising a pore shaped as a centerline, the centerline being longer than two lines of substantially equal length each perpendicular to opposite ends of the centerline, the alternating pattern being configured such that each end of the pore centerline is approximately perpendicular to the centerline of a pore of an adjacent unit cell structure. The scaffold is configured as one or more sheets, and in some embodiments, the sheets each include a first planar side and a second planar side, and in certain aspects, the scaffold includes 1, 2, 3, 4, or 5 sheets, or at least 1, 2, 3, 4, or 5 sheets, or no more than 1, 2, 3, 4, or 5 sheets. In some embodiments, the multiple sheets are configured such that the planar side of one sheet is adjacent to the planar side of another sheet.

[0014] In some embodiments, the scaffold generally comprises one or more defined shapes, such as a line, a curve, a circle, a square, a crescent, a triangle, a rectangle, an oval, a trapezoid, a bowl, etc., or in certain cases, the scaffold comprises markings for one or more of the defined shapes.

[0015] In various embodiments, the polymer substrate comprises polycaprolactone, polydioxanone, or a combination thereof. The one or more ECM materials, in certain cases, comprise a single type of collagen or a combination of one or more types of collagen, and in some cases, the collagen is derived from tendon, rat tail, bovine, porcine, or recombinant. In certain embodiments, the combination of one or more types of collagen comprises type I collagen and type III collagen, and in some cases, the collagen is telocollagen derived from bovine tendon, rat tail tendon, or recombinant.

[0016] In certain embodiments, the scaffold includes a coating included on a first side of the sheet, a second side of the sheet, or both the first and second sides of the sheet. The coating, in certain embodiments, fills the pores of a plurality of unit cell structures of the scaffold, fills the pores of a majority of the unit cell structures of the scaffold, or fills the pores of substantially all of the unit cell structures of the scaffold. The coating, in at least some cases, does not fill the pores of a majority of the unit cell structures of the scaffold, or does not fill the pores of substantially all of the unit cell structures of the scaffold. In certain embodiments, the thickness of the scaffold is 1 mm or less.

[0017] In various embodiments, the scaffold comprises one or more therapeutic agents, which in some embodiments comprise one or more growth factors, one or more cytokines, one or more chemokines, one or more drugs, or combinations thereof.

[0018] Embodiments of the present disclosure include methods of producing any of the scaffolds encompassed herein, the methods comprising: (a) three-dimensionally printing a patterned polymer substrate; (b) applying one or more ECM materials to the substrate; (c) subjecting the substrate to one or more crosslinkers; (d) optionally washing the substrate; and (e) subjecting the substrate to a temperature condition of less than 15°C, where optionally, the one or more ECM materials and one or more crosslinkers are mixed together before being applied to the substrate. The polymer substrate, in some cases, is comprised of polycaprolactone, polydioxanone, or a combination thereof. In certain embodiments, applying comprises immersing the substrate in a solution of the coating, placing the substrate on a solution of the coating, and / or spraying, dripping, and / or placing the coating onto the substrate. Applying can be carried out for, for example, 1 to 24 hours, 5 to 24 hours, 5 to 20 hours, 8 to 20 hours, 8 to 15 hours, or 9 to 11 hours. In certain embodiments, the one or more cross-linking agents are selected from the group consisting of 1,4-butanediol diglycidyl ether (BDDE), hexamethylene diisocyanate (HDMI), glutaraldehyde (GA), genipin, and combinations thereof. In certain cases, (c) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours. In embodiments, washing is with water, and (d) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours in certain aspects. In some embodiments, (e) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours. In at least some cases, following (e), the produced scaffold is subjected to drying.The method may further include applying one or more therapeutic agents to the scaffold in certain cases, such as in the polymer, the coating, or both the polymer and the coating, and / or in certain aspects, applied to at least a portion of the exterior of the scaffold. The degradation of the patterned polymer substrate may, in certain embodiments, be tunable based on the concentration of the crosslinker. The method may, in certain embodiments, include washing the substrate after subjecting the substrate to one or more crosslinkers. The scaffold, in certain embodiments, is generated in a defined shape, such as configured based on mandrel forming or as a 3D-printed pre-programmed macrostructure.

[0019] Embodiments of the present disclosure include methods of reinforcing soft tissue in an individual in need thereof, comprising applying an effective amount of any of the scaffolds encompassed herein to one or more soft tissue sites of the individual. In certain embodiments, the soft tissue may include muscle, tendon, ligament, fascia, fat, skin, nerve, blood vessel, or a combination thereof. In certain aspects, the soft tissue includes an injury, a surgical site, a congenital deformity, diseased tissue, or a combination thereof. In certain embodiments, the soft tissue is soft tissue of the breast, stomach, abdomen, groin, leg, arm, hand, face, pelvis, uterus, vagina, penis, cervix, brain, nose, ear, eyelid, heart, kidney, liver, bladder, prostate, larynx, trachea, or a combination thereof. In certain cases, the soft tissue includes breast tissue for breast reconstruction, breast reduction, or breast augmentation, or the soft tissue includes a hernia. In certain embodiments, applying comprises attaching the scaffold to the individual's soft tissue and / or tissue adjacent to the individual's soft tissue. Attaching is optionally further defined as the use of sutures, staples, or surgical adhesives to attach the scaffold to the individual's soft tissue and / or tissue adjacent to the individual's soft tissue, where the sutures in certain embodiments are purse string sutures, running sutures, interrupted sutures, buried sutures, deep sutures, or subcutaneous sutures. The sutures of the sutures may be absorbable or non-absorbable.

[0020] Embodiments of the present disclosure include a flexible sheet comprising one or more biodegradable polymers and one or more ECM materials, the sheet comprising a plurality of patterned unit cell structures, the plurality of patterned unit cell structures aligned in adjacent rows of a series of vertically alternating unit cell structures, each of the series of vertically alternating unit cell structures generally comprising a shaped pore having a centerline, the centerline being longer than two substantially equal-length lines each perpendicular to opposite ends of the centerline, and the alternating pattern being configured such that each end of the pore centerline is approximately perpendicular to the centerline of a pore of an adjacent unit cell structure. The unit cell structures, in certain embodiments, are comprised of one or more biodegradable polymers, and the sheet comprises a coating of one or more ECM materials. In certain embodiments, the flexible sheet is further defined as a unit cell structure comprising a coating of one or more ECM materials. The pores are optionally filled with the coating, and the one or more ECM materials comprise type I collagen. The sheet, in certain cases, is contained in suitable packaging and, in certain embodiments, is sterile.

[0021] Any embodiment discussed in this specification can be implemented with respect to any method or composition of the present disclosure, and vice versa, and it is contemplated that different embodiments may be combined. Furthermore, the compositions of the present disclosure may be used to achieve the methods of the present disclosure. The claims of the original application are intended to encompass claims that are multiple dependent on any filed claim or combination of filed claims. The present disclosure is not limited to these exemplary embodiments and applications, nor is it limited to the manner in which the exemplary embodiments and applications operate or are described herein. Furthermore, the figures may show simplified or partial views, and the dimensions of elements in the figures may be exaggerated or otherwise not to precise scale.

[0022] Other objects, features, and advantages of the present invention will become apparent from the following Detailed Description. It should be understood, however, that the Detailed Description and the specific examples, while indicating particular embodiments of the present disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this Detailed Description. [Brief explanation of the drawings]

[0023] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The present disclosure may be better understood by reference to one or more of these drawings in combination with the Detailed Description presented herein. [Figure 1A] 10 illustrates an embodiment of a plurality of unit patterns. [Figure 1B] A close-up of an example of multiple unit patterns configured on a 3D printed scaffold. [Figure 1C] Top view of an example scaffold prior to deposition of the extracellular matrix coating. [Figure 1D] One illustration of an example scaffold prior to deposition of the extracellular matrix coating. [Figure 1E] Side view of an example scaffold prior to deposition of the extracellular matrix coating. [Figure 1F] Side view of example scaffolding to demonstrate scale. [Figure 2] Microscopic images of Polyglactin 910 mesh* and PCL Soft Tissue Reinforcement Scaffold (STRS)** at 0 and 6 weeks (*: longitudinal direction, **: pattern P). [Figure 3A] Ultimate Tensile Strength (UTS) of Polyglactin 910 mesh over time (longitudinal direction). [Figure 3B] Young's modulus (YM) of polyglactin 910 mesh over time (longitudinal direction). [Figure 4A] UTS of PCL STRS over time. [Figure 4B] YM of PCL STRS over time. [Figure 5] Enzymatic degradation test results (BDDE x%: collagen matrix with x% BDDE). [Figure 6] UTS graph comparing STRS of the present disclosure with TnR mesh and ADM control (MegaDerm). [Figure 7] Comparison of cell infiltration in ADM versus STRS. [Figure 8] Graph showing control of degradation by adjusting crosslinker concentration. [Figure 9] An example of the STRS manufacturing process. [Figure 10] An example of freeze-drying conditions for one or more actions in the STRS manufacturing process. The "9999" item in the SVP refers to maintaining a constant temperature (different from room temperature) until the sample is collected. [Figure 11] UTS graph comparing different STRS fabricated with either PCL or PDO at a specific line width compared to MegaDerm. [Figure 12] STRS and MegaDerm bubble charts. DETAILED DESCRIPTION OF THE INVENTION

[0024] Unless otherwise defined, scientific and technical terms used in connection with the teachings set forth herein shall have the meanings commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0025] This specification describes exemplary embodiments and applications of the present disclosure. However, the present disclosure is not limited to these exemplary embodiments and applications or to the manner in which the exemplary embodiments and applications operate or are described herein. Other embodiments, features, objects, and advantages of the present teachings will be apparent from the detailed description and accompanying drawings, as well as the claims. Additionally, the figures may depict simplified or partial views, and the dimensions of elements in the figures may be exaggerated or otherwise not to scale. The division of chapters herein is merely for ease of review and does not limit any combination of elements described.

[0026] I. Definition Examples The words "a" or "an" when used in conjunction with the term "comprising" can mean "one," but can also mean "one or more," "at least one," and "one or more."

[0027] Throughout this application, the term "about" is used to indicate that a value includes the inherent variation of error of the measuring or quantification method.

[0028] It is contemplated that any method or composition described herein can be practiced with respect to any other method or composition described herein, and that different embodiments may be combined.

[0029] As used herein, "bioink" may refer to any bioactive, bioprintable, natural or artificially derived material that can be deposited as filaments, fibers, fibrils, droplets, gels / hydrogels, or slurries during an additive manufacturing process and utilized to mimic the extracellular matrix environment and support the adhesion, proliferation, and differentiation of living cells. In certain cases, bioinks may provide materials that facilitate soft tissue reinforcement.

[0030] As used herein, "extracellular," as used with respect to, for example, "extracellular material," "extracellular structure," "extracellular matrix," "extracellular construct," and "extracellular component," can refer to a characteristic that exists outside a cell and can refer to synthetic or natural materials. Examples of materials that are extracellular include synthetic and natural polymers; metabolic products; ions; various proteins and non-protein substances (e.g., DNA, RNA, lipids, microbial products), such as collagen, proteoglycans, hormones, growth factors, cytokines, chemokines; and other substances, such as digestive enzymes (e.g., trypsin and pepsin), extracellular proteinases (e.g., matrix metalloproteinases, a disintegrin and metalloproteinase with thrombospondin motifs), and the like. These include various enzymes, including anti-inflammatory cytokines (ADAMTS), cathepsins, and antioxidant enzymes (e.g., extracellular superoxide dismutase); proteolytic products; extracellular matrix proteins (e.g., elastin, glycosaminoglycans (GAGs), laminin, fibronectin, etc.), selected cell populations, small molecules and small molecule inhibitors, antibiotics, antimicrobial agents, nanoparticles, mesoporous silica, silk fibroin, enzyme degradation sites; antifibrotic agents, such as anti-transforming growth factor beta (anti-TGF-β) and anti-tumor necrosis factor alpha (anti-TNF-α); proangiogenic agents, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF); and factors that affect adipogenesis and proliferation, such as insulin-like growth factor 1 (IGF-1) and dexamethasone.

[0031] The term "pore" as used herein may refer to an opening in a scaffold. A pore may or may not be a particular shape. The shape of a pore may not be circular or square, but may generally be the shape of the letter "I." A pore may include the shape of a centerline, with two shorter perpendicular lines on either side of the centerline.

[0032] As used herein, the term "resorbable" may refer to the ability of a device to undergo biodegradation (chemical degradation by biological agents) and the degradation products being removed by cellular activity in a biological environment.

[0033] As used herein, "scaffold" may refer to a biocompatible and bioresorbable structure used in tissue engineering that can be implanted within the body to provide support and / or promote cell adhesion and tissue regeneration, such as for diseased tissue or wound repair. The scaffold may include a repeating defined unit pattern in adjacent rows. The scaffold may be used in areas of soft tissue, including, for example, regeneration and / or reinforcement of cartilage, skin, organs, muscles, tendons, ligaments, fascia, fat, skin, nerves, blood vessels, or combinations thereof. The scaffold may be utilized in soft tissues of the breast, stomach, abdomen, groin, legs, arms, hands, face, pelvis, uterus, vagina, penis, cervix, brain, nose, ears, eyelids, heart, kidneys, liver, bladder, prostate, larynx, trachea, or combinations thereof. The term "artificial support structure" may be used interchangeably with the term "scaffold" herein.

[0034] As used herein, the terms "unit pattern" and "unit cell structure" may be used interchangeably and may refer to a repeating shape having a defined outline bordered by defined pores. The outline and pores may be generally the same shape. A unit cell structure may be a structure having the overall shape of the letter "I."

[0035] II. Scaffolding and its Use A variety of material options exist for providing tissue reinforcement or fill for excised tissue to reconstruct the natural shape of soft tissue, including areas from which excised tissue was harvested. Examples of materials include acellular dermal matrix (ADM) bioscaffolds derived from decellularized human, bovine, or porcine dermis; fat or other grafted tissue fillers; synthetic polymer-based scaffolds; or combinations thereof. However, certain materials have several drawbacks, including, for example, eliciting adverse immunogenic responses in recipients (e.g., due to ADM); lack of support, protection, and reinforcement for the dermal layer to maintain shape or support; and lack of the ability to provide a robust cellular infiltration / remodeling response after implantation.

[0036] Certain biological scaffolds may not provide a composition of extracellular matrix proteins that facilitates cell ingrowth into the biological scaffold, and therefore, such scaffolds may not enhance tissue regeneration that can aid in patient recovery. In certain embodiments, the compositions of the present disclosure utilize a combination of a 3D printed polymer scaffold and animal-derived collagen in a specific pattern as an improvement over other synthetic scaffolds by providing natural mechanical tissue properties that other synthetic scaffolds lack.

[0037] Disclosed herein are compositions, methods, and materials related to implantable acellular scaffolds containing natural extracellular matrix (ECM) proteins that can elicit a robust regenerative response while minimizing an undesirable immunogenic response from the host. Such scaffolds can provide support to wounds or fill voids after surgery, in addition to enhancing host cell ingrowth, regeneration, and repair.

[0038] The present disclosure relates to three-dimensional printing of various macroscopic scaffold shapes based on bioprinting constructs, including at least flat sheets and / or 3D scaffold structures. The scaffold compositions can provide cushioning and structural support, supplemental support, protection, reinforcement, and coverage for other tissues within any soft tissue, including muscle, tendon, ligament, fascia, fat, skin, nerve, blood vessel, or combinations thereof. The soft tissue can be located anywhere within the body, and the scaffold can be configured to stimulate host cell remodeling.

[0039] The scaffold can be biodegradable or resorbable. It can be utilized to support, repair, lift, and reinforce defects where weaknesses or voids exist in the soft tissue (or where both weaknesses and voids exist) requiring the addition of material. The scaffold can, for example, facilitate the repair of defects requiring the addition of reinforcing, regenerating, and / or bridging materials to achieve a desired surgical outcome.

[0040] In various embodiments, the scaffold composition may minimize host immunogenic responses, given that the scaffold may contain user-selected or desired components. Unlike current acellular dermal matrix (ADM) products, which can trigger a "graft-versus-host response," the various scaffold compositions encompassed herein allow for control of the components, enabling standardization of clinical outcomes within and between patients. The scaffold provides increased support and reinforcement compared to other available products, and the scaffold may provide controlled and enhanced elasticity and tensile strength relative to products currently available in the art. Utilizing 3D printing and this specific pattern / material combination has the potential to replicate natural mechanical tissue properties not possible with other synthetic scaffolds.

[0041] The present disclosure relates to printable scaffold compositions that mimic acellular matrix products but possess inherent printability into 2D and 3D shapes and the ability to support tissue and / or organ growth. The scaffold compositions described herein are improved because, at a minimum, they minimize concerns about donor availability, provide reproducibility, mitigate increased costs, eliminate concerns about tissue quality, variability, and potential for contamination, and provide a product with minimal immunogenicity. The scaffold (including unit cell pattern and material) can also be tailored to impart different mechanical properties as required by the end user depending on clinical need, which cannot be done with other synthetic scaffolds or allograft / xenograft tissues. The scaffold may also be configured for permanent use within the body.

[0042] The scaffolds encompassed herein can provide the necessary porosity to allow cell infiltration, provide a niche large enough for cells to attach, and ultimately direct cell fate toward a remodeling / regenerative phenotype. Furthermore, from a mechanical / structural perspective, the scaffolds contain multiple specific unit cell structures, the arrangement of which within the scaffold structure provides the appropriate mechanical strength and elasticity for the scaffold to be physiologically relevant and useful as a support matrix. These characteristics can be provided by the scaffold structure using the extracellular material compositions disclosed herein, such as, for example, an extracellular material composition comprising collagen I, thereby providing the necessary structural integrity and healing properties.

[0043] The unit cell structural configuration of the scaffold imparts specific physical properties to the scaffold, and the construct may have an engineered microarchitecture (e.g., controlling properties such as porosity, fiber diameter, spacing, matrix height, fiber orientation, etc.) and a consistent surface topography throughout that provides a suitable scaffold for robust wound healing, regeneration, infiltration, and / or remodeling responses.

[0044] Additionally, the constructs may provide, for example, cushioning and structural and mechanical support for other tissues, supplemental support, protection, reinforcement, and coverage within soft tissues, while stimulating host cell remodeling.

[0045] A. Scaffold Materials Scaffold compositions are provided that may include one or more biodegradable polymers, one or more extracellular matrix materials, and, optionally, other components such as one or more therapeutic agents. The unique combination of biodegradable polymers and extracellular matrix materials together provides a suitable support matrix for remodeling and a fertile environment for cell infiltration. The combination of polymer and biological construct material also provides a robust scaffold for the addition of other molecular moieties, in various embodiments.

[0046] The scaffold may comprise natural and / or synthetic polymers, including any polymer that provides mechanical stability and may have a consistent degradation profile, allowing for greater predictability for individuals receiving the scaffold. The scaffold composition may comprise any suitable natural or synthetic polymer, or a combination or blend thereof. Synthetic polymers may be biodegradable and may include, for example, polycaprolactone (PCL), poly(p-dioxanone) (PDO), combinations thereof, or any other type of polymer.

[0047] Deposition of the polymer of the unit cell structure can be performed, for example, by a bioprinter using components such as, for example, a nozzle or syringe. These components can be, for example, pneumatic, piston, or screw-driven. For example, a pneumatically driven syringe can deposit liquefied polymer in successive layers to generate a construct that will eventually be crosslinked.

[0048] Synthetic polymers can be deposited by 3D printers as bioinks. Bioinks may or may not contain bioactive molecules. Compared to traditional polymer-based compositions, certain bioinks containing bioactive molecules in addition to polymers may need to be deposited under gentler conditions than the polymer-based composition. This may be due to the relatively more delicate nature of the bioink structure (e.g., higher water content, amorphous structure, etc.). Therefore, bioprinting process parameters such as printing pressure or nozzle / syringe diameter can be considered when reducing shear stress for some bioinks to prevent damaged or lysed cells, which can affect cell viability in the bioink. Other parameters that can be considered and controlled accordingly include, for example, printing temperature (e.g., lower than for polymer-based compositions), uniformity of diameter of the filaments that make up the unit cell, angle of filament interaction, bleed-through of filaments at intersections, and maintaining shape fidelity after printing but before crosslinking with the polymer-based composition. In either case, the polymer may be deposited, for example, as a droplet or a stream, utilizing defined process parameters to ensure scaffold fabrication while maintaining the structural integrity of the deposited composition.

[0049] Each unit cell of the scaffold structure may include a polymer or blend of polymers and may include an ECM material coating that may or may not include collagen. It is understood that the extracellular material of the scaffold structure, which may include PCL and / or PDO and / or another dissolvable or liquefiable polymer, may help provide structural integrity and function to the scaffold structure and the unit cells that make up the structure.

[0050] The extracellular matrix components of the scaffold may include one or more of collagen (e.g., collagen 1 (Col-1), and optionally other types of collagen), extracellular matrix proteins (e.g., laminin, fibronectin, elastin, glycosaminoglycans, or combinations thereof), growth factors, cytokines, selected cell populations, small molecules, small molecule inhibitors, antibiotics, antimicrobial agents, nanoparticles, mesoporous silica, silk fibroin, and enzymatic degradation sites.

[0051] The scaffold may, in certain embodiments, include an ECM material coating in place of a collagen coating, a collagen coating, or a combined collagen / ECM material coating.

[0052] B. Scaffolding Shape and Structure The present disclosure relates generally to scaffold structures that may include unit cells. More specifically, there is a need for porous extracellular structures and / or scaffold structures having a porous architecture suitable for promoting cell infiltration, tissue regeneration, and minimizing the risk of adverse immune responses in and / or pathogen contamination of a patient.

[0053] The scaffold of the present disclosure includes multiple unit parts of defined shapes and structures. The scaffold may be composed of multiple unit cell structures arranged or constructed in a regular or defined pattern. The scaffold may be composed of multiple unit patterns, which may also be referred to as unit cell structures, each containing multiple filaments arranged continuously, symmetrically, and regularly. Each unit pattern may be constructed from edges or contours of closed shapes that form holes inside. Multiple unit patterns within a scaffold may be connected to each other with intersections, and the number of intersections may be the same as the number of edges passing through the intersections (FIG. 1A). As shown in FIG. 1A, for a unit pattern 100, the number of intersections 101 is the same as the number of edges / lines 102 at a particular intersection 101.

[0054] A scaffold may be considered an artificial support structure comprising a plurality of unit patterns, each comprising a plurality of filaments, that are repeatedly arranged to establish symmetrical rows or columns. In such cases, each unit pattern may be comprised of a closed shaped edge that creates pores therein, and the columns or columns in which the plurality of unit patterns may be repeatedly arranged have an Eulerian path.

[0055] The scaffold may comprise a patterned polymeric substrate having a coating of one or more ECM materials, wherein the pattern of the polymeric substrate may include a series of adjacent rows of unit cell structures, each generally shaped like the letter "I." In such cases, the unit cell structures may be aligned within the rows of the patterned polymeric substrate in a vertically alternating pattern of unit cell structures. The series of unit cell structures may be further defined as including a pore shaped as a centerline, the centerline being longer than two substantially equal-length lines each perpendicular to opposite ends of the centerline, and the alternating pattern within the scaffold may be configured such that each edge of the pore centerline is approximately perpendicular to the centerline of a pore of an adjacent unit cell structure.

[0056] Figure 1B shows a magnified image of an example bioprinted scaffold prior to the deposition of one or more ECM materials thereon. The filaments that make up the outline of the I-shaped unit cell structure can be deposited by a 3D printer using a specific line width. Figures 1C and 1D provide different angles of an image of an entire sheet of scaffold with the same unit cell structure configuration as Figure 1B. A given row or column within the scaffold may or may not be approximately diagonal to the edge of the scaffold structure. Figures 1E and 1F provide different angle images of the side of a sheet of scaffold. The thickness of the scaffold can be predetermined by the deposition of the 3D-printed polymer.

[0057] Degradation of the scaffold composition can occur over time after surgical implantation, and can occur partially or completely over at or about 6, 7, 8, 9, 10, 11, or 12 months. Degradation of the scaffold composition can occur partially or completely over 6-12, 6-11, 6-10, 6-9, 6-8, 6-7, 7-12, 7-11, 7-10, 7-9, 7-8, 8-12, 8-11, 8-10, 8-9, 9-12, 9-11, 9-10, 10-12, 10-11, or 11-12 months. Degradation of the scaffold composition can occur partially or completely over 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more years, or over about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more years. Degradation of the scaffold composition may occur over 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-10, 8-9, or 9-10 years. or over about 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 2 to 10, 2 to 9, 2 to 8, 2 to 7, 2 to 6, 2 to 5, 2 to 4, 2 to 3, 3 to 10, 3 to 9, 3 to 8, 3 to 7, 3 to 6, 3 to 5, 3 to 4, 4 to 10, 4 to 9, 4 to 8, 4 to 7, 4 to 6, 4 to 5, 5 to 10, 5 to 9, 5 to 8, 5 to 7, 5 to 6, 6 to 10, 6 to 9, 6 to 8, 6 to 7, 7 to 10, 7 to 9, 7 to 8, 8 to 10, 8 to 9, or 9 to 10 years. Integration of host cells into the porous scaffold can proceed throughout the degradation process, as the infiltrating cells will degrade the polymer and secrete their own extracellular matrix in an attempt to regenerate the tissue.The scaffold composition degradation profile is definable and predictable across manufacturing lots, which is an improvement over acellular dermal matrix constructs currently available in the art.

[0058] A plurality of connected unit cells within the scaffold structure may form a substantially planar sheet.

[0059] The artificial support structure or scaffold may include specific dimensions and / or mechanical properties that can impart natural mechanical tissue properties. The composition may have a specific thickness, such as about 0.5 mm to about 1.5 mm, about 0.7 mm to about 1.3 mm, or about 0.9 mm to about 1.1 mm. In some cases, a layer of the composition may have a thickness of about 0.10 mm to about 0.3 mm, about 0.15 mm to about 0.25 mm, or about 0.18 mm to about 0.22 mm. When multiple layers are utilized, the individual layers may or may not have the same thickness. For filaments of the composition, they may have a diameter of less than about 550, about 500, or about 400 microns.

[0060] The artificial support structure or scaffolding may have an ultimate tensile strength of about 4 MPa to about 5 MPa, about 4.05 MPa to about 4.7 MPa, or about 4.12 MPa to about 4.50 MPa. With regard to modulus of elasticity, any composition may have a modulus of elasticity of about 2.8 MPa to about 4.2 MPa, about 3.00 MPa to about 4.10 MPa, or about 3.06 MPa to about 4.00 MPa. The artificial support structure or scaffolding may be attached to soft tissue in any manner, including by suture, and the suture retention strength may be about 20 N to about 26 N, about 21 N to about 25 N, or about 22.03 N to about 24.27 N. Regarding additional mechanical properties, the artificial support structure may have a burst strength of about 140 N to about 170 N, about 145 N to about 163 N, or about 147.14 N to about 161.26 N, and / or a tear resistance of about 18 N to about 26 N, about 19 N to about 25 N, or about 19.87 N to about 24.92 N.

[0061] Scaffolds can be printed in a desired shape in advance of their need, such as being placed in a warehouse or sold commercially. In such cases, the surface of the scaffold can be 2D, and the printed scaffold can be 3D, a prefabricated shape, or customized to a specific patient's needs, such as a patient's specific wound or void requiring personalized adaptation. The shape of the scaffold can be based on a mandrel or a preprogrammed macrostructure to be 3D printed. The design of the scaffold shape can be generated using computer-aided manufacturing (CAM) software prior to manufacturing. The scaffold can be in the shape of a sheet, such as a square or rectangle, or can be a bowl or other 3D microstructure shape that fits the patient's anatomy. The sheet can be cut to a specific size and / or shape based on the patient's needs. The scaffold can be stored or sold commercially in any form, including sheet form or a printed 3D structure.

[0062] C. Additional Scaffold Components The scaffolds of the present disclosure can be manufactured such that their structure includes one or more therapeutic or other agents. The agents can be eluted from the scaffold as part of a coating on the scaffold, a combination thereof, or the like. The agents can be useful, for example, as therapeutic agents for tissue adjacent to the scaffold, tissue near the scaffold, etc., for wound healing, diseased tissue healing, etc. The scaffold can be configured to be resorbable (as described above) over a period of time, allowing for delivery of the agent over that period. The agent can be utilized for wound healing, scar prevention, fibrosis prevention, and / or long-term treatment for chronic or recurring medical conditions. Release of the agent from the scaffold can be modified, such as immediate release, sustained release, delayed release, or controlled release, in which the rate of agent release can be controlled.

[0063] Drugs can be provided on one or more external surfaces of the scaffold and / or incorporated within the scaffold. Drugs can be mixed with a precursor polymer solution and incorporated into the polymer matrix during fabrication, with release occurring upon polymer degradation. Drugs can be incorporated into the device by placing the device in a solution of drug and allowing the drug to adsorb to the device surface with release controlled by desorption rate. Drugs can be covalently grafted to functional groups on the device polymer chains. The covalently attached group can be selected to be a labile group, e.g., an ester group or a thio-β ester group, which will be cleaved in a physiological environment to release the drug. Drugs can be incorporated into the ECM coating.

[0064] The period of time during which the drug is eluted from the scaffold is substantially the same as the period of use of the scaffold, including the period during which at least a portion of the scaffold is resorbed by the body. Substantially all of the drug may be eluted from the scaffold before partial or complete resorption by the body, in which case a sufficient amount of drug will be available to provide adequate healing at the site of use.

[0065] The one or more therapeutic agents can be any type of therapeutic agent suitable for the individual receiving the composition for any purpose. The agent associated with the composition can be tailored to the individual's therapeutic needs. For example, an individual may require a specific agent as part of the composition based on the individual's medical condition, and a composition containing the agent is manufactured accordingly. An individual may require a specific agent as part of the composition based on the individual's medical condition, and a composition containing the desired agent can be already manufactured and obtained, such as when stored, commercially available, etc.

[0066] The therapeutic agent may be a bioactive molecule, growth factor, cytokine, chemokine, drug, hormone, antibiotic, analgesic, hemorheological agent, vasoconstrictor, anti-inflammatory agent, antifibrotic agent, wound healing agent, radioprotective material, antifungal agent, contraceptive, or any combination thereof. When the therapeutic agent is a growth factor, the growth factor may be epidermal growth factor, keratinocyte growth factor, transforming growth factor including TGF-α, TGF-β1, and TGF-β2, vascular endothelial growth factor, platelet-derived growth factor, blocking factor, scavenger, antagonist, differentiation factor, or agent that binds to a specific promoter. When the therapeutic agent is a cytokine, the cytokine may be interleukin-2 (IL-2), IL-7, IL-15, or a combination thereof. When the therapeutic agent is a chemokine, the chemokine may be any one or more of the chemokines in the following subclasses: CXCL-, CCL-, CX3-, and XCL-. Specific examples of chemokines include CXCL1, CXCL2, CXCL3, CXCL4, CXCL4L1, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL15, CXCL16, CXCL17, CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL10, CCL11, CCL12, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CX3CL1, XCL1, XCL2, or combinations thereof. When the therapeutic agent is a drug, the drug may be a small molecule, an antibody, a nucleic acid, a polypeptide, a carbohydrate, or a combination thereof. In certain cases where the therapeutic agent is a drug, the drug may be an analgesic, an anesthetic, an antibacterial, an antifungal, an antiviral, an anti-inflammatory, a hormone, a vitamin, a mineral, an immunological agent, or a mixture thereof.

[0067] The drug may be a hormone, antibiotic, analgesic, hemorheological agent, vasoconstrictor, anti-inflammatory agent, antifibrotic agent, wound healing agent, radiation protection material, antifungal agent, contraceptive, or any combination thereof. In certain cases, the drug is a drug such as AMD3100, tacrolimus, 2-octyl cyanoacrylate, Alevicyn, Artiss, becaplermin, betaine / polyhexanide, or cadexomer iodine. Collagenase, Dermabond, Eleton Cream, Episalvan, Evicel, fibrin sealant, Filsbes, topical hypochlorous acid, Rhodosorb, Nexobrid, Oleogel-S10, topical petrolatum and mineral oil, Prontosan, protease, Regranex Gel, Santil, Tachosil, Tisil VH, Tropazone, or a combination thereof. When the drug is a hormone, the hormone may be estrogen.

[0068] Optionally, the scaffold composition may include one or more growth factors, such as GM-CSF, NGF, SCF, TGF-β, EGF, VEGF, and the like, or any one or combination thereof.

[0069] The scaffold composition may further comprise one or more cytokines, such as, for example, any one or combination of IL-1, IL-4, IL-5, IL-6, IL-9, IL-13, IL-18, IL-25, IFN-α, IFN-β, and the like.

[0070] Optionally, the scaffold may further comprise one or more antibiotics. Suitable antibiotics include macrolides (e.g., azithromycin, clarithromycin, and erythromycin), tetracyclines (e.g., doxycycline, tigecycline), fluoroquinolones (e.g., gemifloxacin, levofloxacin, ciprofloxacin, and moxifloxacin), cephalosporins (e.g., ceftriaxone, defotaxime, ceftazidime, cefepime), penicillins (e.g., ampicillin-sulbactam, piperacillin-tazobactam, and ticarcillin, including clavulanic acid), optionally with a β-lactamase inhibitor (e.g., sulbactam, tazobactam, and clavulanic acid). amoxicillin, amoxicillin with clavulanic acid, ampicillin, piperacillin, and ticarcillin), aminoglycosides (e.g., amikacin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, rhodostreptomycin, streptomycin, tobramycin, and apramycin), penems or carbapenems (e.g., doripenem, ertapenem, imipenem, and meropenem), monobactams (e.g., aztreonam), oxazolidinones (e.g., linezolid), vancomycin, glycopeptide antibiotics (e.g., telavancin), Mycobacterium tuberculosis antibiotics, and the like.

[0071] The scaffold composition may be formulated to contain antibacterial, antifungal agents (e.g., polyene antifungals such as amphotericin B; triazole antifungals such as itraconazole, ketoconazole, fluconazole, voriconazole, clotrimazole, isavuconazole, miconazole, and posaconazole; echinocandin antifungals such as caspofungin, micafungin, and anidulafungin; orotate dehydrogenase inhibitors such as F901318). The compositions may further comprise one or more antimicrobial agents, including an antifungal agent (e.g., oseltamivir, zanamivir, amantadine, rimantadine, ribavirin, ganciclovir, valganciclovir, foscavir, cytomegalovirus immune globulin, pleconaril, rupintrivir, palivizumab, motavizumab, cytarabine, docosanol, denotivir, cidofovir, and acyclovir), an antiparasitic agent, or a combination thereof.

[0072] The scaffold composition may further comprise one or more pro-angiogenic (e.g., VEGF, PlGF) bioactive molecules to promote angiogenesis in patients with or without compromised vasculature.

[0073] The scaffold composition may further comprise one or more anti-fibrotic molecules (anti-TGFβ, anti-TNF-α), such as to reduce fibrosis in the patient at the implant site.

[0074] The scaffold composition may further comprise one or more factors that affect adipogenesis and proliferation (eg, IGF-1, dexamethasone) to promote the growth of grafted adipocytes.

[0075] III.How to use The present disclosure includes scaffold compositions and methods for any type of tissue care, including the treatment of wounds, diseased tissue, or any type of medical condition affecting the location of soft tissue in vivo. The scaffold can be utilized by any person in need thereof, but the scaffold may be for a mammal, including a human, and the human may have soft tissue in need of the scaffold. The individual in need may have wounded soft tissue, diseased soft tissue, soft tissue requiring post-operative treatment, soft tissue requiring peri-operative treatment requiring gender reassignment surgery, and / or soft tissue where a medical condition has resulted in the need for soft tissue treatment. The wound may be internal or external and may result from trauma, disease, laceration, circulatory disorder, nerve disorder, surgical procedure, etc. Intra- or post-operative treatment may require the use of a scaffold from obstetric surgery or procedures, male-to-female gender reassignment surgery, breast reconstruction, hernia repair, etc. The scaffold may, in some cases, be used for reconstructive or cosmetic purposes.

[0076] Scaffolds may be obtained pre-fabricated or may be manufactured according to the needs of the scaffold. In either case, the type of need and / or size of the individual receiving the scaffold may be considered prior to the manufacture or selection of the device. The individual receiving the scaffold may be a child (up to 12 years of age), an adolescent (12-18 years of age), or an adult. Some or all of the scaffold may be designed or configured to be utilized for permanent use, while portions of the scaffold may be designed or configured to disappear or dissolve over time, including being resorbed by the body.

[0077] Degradation of some or all of the scaffold may or may not coincide with the timing of healing, for example, the tissue may be healed before resorption of some of the scaffold, or may not be completely healed before resorption of some of the scaffold, and then additional treatment may be utilized, if necessary.

[0078] Specific examples of uses of the device include use in intra-operative, post-operative, and / or post-radiation therapy settings, such as to facilitate wound healing or prevent scarring or obstruction. In any event, specific examples include at least post-radiation and / or surgery treatment, any type or degree of fibrosis and its treatment or prevention, post-operative treatment, physical damage or injury, tissue shortening and / or tightening due to surgery and / or radiation, cervical incompetence, vaginal / uterine prolapse, or a combination thereof.

[0079] The present disclosure provides a method for reinforcing soft tissue in an individual in need thereof, which may include applying an effective amount of a scaffold to one or more soft tissue sites of the individual. The soft tissue may include, for example, muscle, tendon, ligament, fascia, fat, skin, nerve, blood vessel, or a combination thereof. The soft tissue may include an injury, a surgical site, a congenital deformity, diseased tissue, or a combination thereof. In particular, the soft tissue may be soft tissue of the breast, stomach, abdomen, groin, leg, arm, hand, face, pelvis, uterus, vagina, penis, cervix, brain, nose, ear, eyelid, heart, kidney, liver, bladder, prostate, larynx, trachea, or a combination thereof. The soft tissue may include breast tissue for breast reconstruction, breast reduction, or breast augmentation.

[0080] The scaffold can be applied to the soft tissue of an individual in any suitable manner. Application can include attaching the scaffold to the soft tissue of an individual and / or attaching the scaffold to tissue adjacent to the soft tissue of an individual. Attaching can include the use of suturing, stapling, and / or surgical adhesive to attach the scaffold to the soft tissue of an individual and / or tissue adjacent to the soft tissue of an individual. The wound or void to be repaired (or both within the same tissue) can determine the type of attachment; if suturing is used, the suture can be, for example, a purse string suture, a running suture, an interrupted suture, a buried suture, a deep suture, or a subcutaneous suture. The suture for suturing can be absorbable or non-absorbable.

[0081] IV. Method of Manufacturing Fabrication of a scaffold can include, at least in part, a series of ordered actions. The method generally includes generating a scaffold by a bioprinter (synthetic polymers) separately from preparing one or more ECM materials (natural polymers, including those utilizing collagen, in at least some cases), which are then combined with a crosslinking agent. Following combination of the synthetic and natural polymers, the combination is subjected to an effective amount of crosslinking agent, followed by washing (optional), and then lyophilization.

[0082] Methods of producing scaffolds encompassed by the present disclosure may include (a) three-dimensionally printing a patterned polymer substrate; (b) applying one or more ECM materials to the substrate; (c) subjecting the substrate to one or more crosslinking agents; (d) optionally washing the substrate; and (e) subjecting the substrate to freeze-drying conditions, such as a temperature below 15°C, optionally where the one or more ECM materials and one or more crosslinking agents are mixed together before being applied to the substrate.

[0083] The scaffold can be bioprinted using a suitable synthetic biodegradable polymer, such as PCL, PDO, or a combination thereof. Bioprinting the polymer can produce a unit cell structure, generally formed as an "I"-shaped filament profile with similarly shaped pores, according to a specific pattern. The line width of the filament can be optimized and can be approximately 400 μm for PCL and approximately 500 μm for PDO. In a separate step, one or more ECM materials (again, natural polymers in some cases) can be prepared or obtained and mixed with an effective amount of a crosslinker (the one or more crosslinkers selected from the group consisting of 1,4-butanediol diglycidyl ether (BDDE), hexamethylene diisocyanate (HDMI), glutaraldehyde (GA), genipin, and combinations thereof) to produce a coating for the scaffold. Following this, the coating mixture to be applied onto the scaffold is applied to the scaffold in any suitable manner, such as by dipping the scaffold into a solution of the coating, placing the scaffold on a solution of the coating, spraying the coating onto the scaffold, dripping the scaffold onto the coating, or placing the coating on a substrate.

[0084] The application of one or more ECM materials and / or one or more crosslinking agents can be carried out for any suitable period of time, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours. The application may be performed for 6-10, 6-8, 8-24, 8-20, 8-18, 8-16, 8-12, 8-10, 10-24, 10-18, 10-16, 10-12, 12-24, 12-18, 12-16, 16-24, 16-20, 16-18, 18-24, 18-20, or 20-24 hours. The application may crosslink one or more ECM materials to the polymer scaffold. The final concentration of ECM material in the applied solution may be about 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, or 1.5 w / v%. The final concentration of ECM material in solution can range from about 0.5-1.5, 0.5-1.2, 0.5-1, 0.5-0.07, 0.07-1.5, 0.07-1.2, 0.07-1, 1-1.5, 1-1.2, or 1.2-1.5 w / v%. The final concentration of crosslinker in the applied solution can be about 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.15, 0.16, 0.17, 0.18, 0.19, or 0.2 v / v%. The final concentration of the cross-linker in the solution can range from about 0.05-0.2, 0.05-0.15, 0.05-0.1, 0.07-0.2, 0.07-0.1, or 0.1-0.2 v / v%.

[0085] Once crosslinking is complete, excess coating solution can be washed from the scaffold substrate (e.g., in any type of water, including tertiary distilled water, salt-free distilled water, and salt-free ultrapure water). Washing can be performed 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more times, including 1-10, 1-8, 1-6, 1-4, 1-2, 2-10, 2-8, 2-6, 2-4, 4-10, 4-8, 4-6, 6-10, 6-8, or 8-10 times, to remove residual crosslinker contained in the scaffold. Residual crosslinker can cause toxicity in the human body, and up to 2 ppm of residual crosslinker can be present in the scaffold. Thus, the washing can be carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours. This can be carried out for 6-10, 6-8, 8-24, 8-20, 8-18, 8-16, 8-12, 8-10, 10-24, 10-18, 10-16, 10-12, 12-24, 12-18, 12-16, 16-24, 16-20, 16-18, 18-24, 18-20, or 20-24 hours. After washing, the scaffold is subjected to lyophilization, which can be carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours or more. Freeze-drying: 1-24, 1-18, 1-12, 1-10, 1-8, 1-6, 1-2, 2-24, 2-18, 2-16, 2-12, 2-10, 2-8, 2-6, 2-3, 4-24, 4-20, 4-18, 4-12, 4-10, 4-8, 4-6, 6-24, 6-20, 6-18, 6-12 , 6 to 10, 6 to 8, 8 to 24, 8 to 20, 8 to 18, 8 to 16, 8 to 12, 8 to 10, 10 to 24, 10 to 18, 10 to 16, 10 to 12, 12 to 24, 12 to 18, 12 to 16, 16 to 24, 16 to 20, 16 to 18, 18 to 24, 18 to 20, or 20 to 24 hours.The manufacturing process may include two freeze-drying processes, where the first freeze-drying process is carried out for the cross-linking process of the natural polymer and matrix formation, and the second freeze-drying process is carried out for re-drying of the scaffold after the residual cross-linking agent is removed.

[0086] One or more therapeutic agents may be utilized in the scaffold, such that the manufacturing method may include applying one or more therapeutic agents directly or indirectly to a portion or all of the scaffold. The one or more therapeutic agents may be present in the polymer, 3D printed with the polymer as it is being 3D printed, in the crosslinking solution, and / or with one or more ECM materials, a combination of being printed with the polymer and being in the crosslinking / ECM solution, and / or applied to at least a portion of the exterior of the scaffold after fabrication of the scaffold. The therapeutic agent may be fabricated with the scaffold, or may otherwise be placed on the scaffold in such a manner that it does not remain on or with the scaffold, but may become part of the surrounding environment to promote healing, cellular infiltration into the scaffold, cell migration to a wound or lesion site, cell or tissue regeneration, and the like. The manufacturing process takes into account the concentration of the therapeutic agent for the scaffold when considering the amount that will be therapeutically effective in the surrounding soft tissue.

[0087] The manufacturing of the scaffold can be designed so that the degradation of the scaffold can be adjusted based on at least the concentration of the crosslinker, the concentration of the natural polymer decellularized extracellular matrix (dECM) solution, the type of crosslinker used, or a combination thereof. For patient needs requiring or benefiting from a slower degradation rate, a higher concentration of crosslinker and / or a longer crosslinking period can be utilized during manufacturing. For patient needs not requiring a slower degradation rate, a lower concentration of crosslinker can be utilized. The crosslinker concentration for standard manufacturing practices can be approximately 0.1%.

[0088] The scaffold can be printed into a defined desired 2D or 3D shape, or each type can be used at a specific soft tissue site where it is needed. Examples of printed 2D shapes include, for example, lines, curves, circles, squares, crescents, triangles, rectangles, ellipses, and trapezoids. Examples of 3D shapes include spheres, pyramids, cubes, rectangular prisms, cylinders, cones, triangular prisms, bowls, or can be customized to fit the wound or void (or both) at the soft tissue site. In some cases for 2D shapes, the sheet can include one or more markings for one or more of the shapes.

[0089] After fabrication, the resulting scaffold can be sterilized and packaged to protect it from contamination by external microorganisms or infestation by organisms such as insects. The packaging can also eliminate the risk of stress or shock in a particular environment prior to use.

[0090] V. Kit Kits comprising a scaffold of the present disclosure or compositions for producing a scaffold of the present disclosure, such as PCL, PDO, both PCL and PDO, and one or more crosslinkers, are encompassed by the present disclosure.

[0091] The kit may include one or more components, any of which may be individually packaged or placed in a container, such as a package, tube, bottle, vial, syringe, or other suitable container means. The kit may include a scaffold or a composition for generating a scaffold, such as one sealed in a package containing a sterile environment, and the kit may also optionally include one or more therapeutic agents contained in a tube, bottle, vial, syringe, etc. In some cases, the one or more therapeutic agents in the kit are included in one or more compositions for generating a scaffold.

[0092] Individual therapeutic components can be provided in concentrated amounts in the kit, with components individually provided at the same concentration as when in solution with the other components. Concentrations of components can be provided, for example, at 1x, 2x, 5x, 10x, or 20x or more. Examples include, at least, hormones, antibiotics, analgesics, hemorheological agents, vasoconstrictors, anti-inflammatory agents, anti-fibrotic agents, wound healing agents, radiation protection materials, antifungals, contraceptives, or any combination thereof.

[0093] The kit may be configured to allow placement of a therapeutic agent on the scaffold at or prior to the time of healing. VI. Working Examples The following examples are included to demonstrate specific compositions and methods of the present disclosure. It should be recognized by those skilled in the art that the techniques disclosed in the following examples represent techniques discovered to work well in the practice of the methods and compositions of the present disclosure, and therefore can be considered to constitute specific modes for its practice. However, those skilled in the art will, in light of the present disclosure, understand that many changes can be made in the specific embodiments disclosed and still obtain like or similar results without departing from the spirit and scope of the subject matter of the present disclosure.

[0094] Example 1 Characterization of soft tissue reinforcement scaffolds The soft tissue reinforcement scaffold (which may be referred to as a STRS) may be characterized by the following studies.

[0095] The scaffold may maintain one or more desired mechanical properties better than a control for at least a particular period of time, such as at least about 4, 6, 8, 10, 12, 24, 36, or 48 hours, and including at least about 3, 4, 5, 6, or 7 days, and including at least about 1, 2, 3, or 4 weeks, and including at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months or more.

[0096] In one example of mechanical properties, hydrolysis can be characterized. Scaffolds were subjected to hydrolysis in PBS at 37°C for 6 weeks. In this study, mechanical properties such as ultimate tensile strength (UTS) and Young's modulus (YM) were observed, and microscopic images of degradation were taken at 0 and 6 weeks. The control group utilized was polyglactin 910 mesh (longitudinal), and the test scaffolds were polycaprolactone (PCL) STRS.

[0097] The microscopy results are provided in Figure 2. The PCL STRS structure retained its original shape at 6 weeks. However, the structure of the polyglactin 910 mesh did not maintain at the same time point. Figures 3A and 3B provide the degradation profile for the polyglactin 910 mesh, and Figures 4A and 4B provide the degradation profile for the PCL STRS structure. For the polyglactin 910 mesh, both UTS and YM could not be measured at 6 weeks and were therefore considered to be 0 (UTS, YM reduction rate (%) = 100). However, the PCL STRS maintained adequate UTS and YM for 6 weeks after the degradation experiment. Therefore, the PCL STRS could satisfy an example of a critical to quality (CTQ) criterion, confirming that PCL is a suitable material for fabricating STRS.

[0098] One example of a biological component of STRS, enzymatic degradation, was characterized. A non-crosslinked extracellular collagen matrix derived from pigs was used as a control for the enzymatic degradation test. The degradation period was compared between the non-crosslinked extracellular collagen matrix derived from pigs and collagen matrices produced with different concentrations of the crosslinker 1,4-butanediol diglycidyl ether (BDDE) using the same units of collagenase. Figure 5 shows the degradation profiles of the non-crosslinked extracellular collagen matrix derived from pigs and the native polymer matrix produced using different concentrations of BDDE. The enzymatic degradation test was performed using 100 U of collagenase, and the values ​​for the non-crosslinked extracellular collagen matrix derived from pigs are the average of two different lots. The total sample size for XCM was 9, and the sample size for each BDDE concentration was 5.

[0099] Comparing the degradation profiles, the matrix with 0.06% BDDE had a faster degradation profile than the non-crosslinked extracellular collagen matrix derived from pigs, and the matrix with 0.1% BDDE had a similar degradation profile to the non-crosslinked extracellular collagen matrix derived from pigs. Finally, the matrix with 0.2% BDDE had a slower biodegradation period than the non-crosslinked extracellular collagen matrix derived from pigs. Regarding the biodegradation period, 0.1% BDDE and 0.2% BDDE can be used as examples.

[0100] BDDE is a cytotoxic substance that can cause side effects in the human body. The amount of residual BDDE can be controlled to less than 2 ppm (the maximum allowable amount according to FDA standards) and used as little as possible for safety reasons. Furthermore, the cleaning process to meet the standards can vary depending on the initial BDDE concentration. Taking various factors into consideration, we selected 0.1% BDDE, which has the same degradation profile as a non-crosslinked extracellular collagen matrix derived from pigs, as an example, and set the number of washes for the STRS cleaning process to five.

[0101] Figure 6 provides a UTS graph comparing the test STRS with the commercially available products MegaDerm (L&C BIO) (acellular dermal matrix (ADM) control) and TnR Mesh (T&R Biofab). The test STRS has a claimed unit structure pattern (unit structures generally resembling an "I") and is compared to a product (TnR Mesh) with the same materials but a different pattern of unit structures. Clearly, the test STRS has a curve that more closely resembles the MegaDerm curve (ADM control) in the first 2 mm of the graph. This similarity of the curves indicates that the STRS product behaves more closely to the ADM control and, therefore, is easier to replace.

[0102] Example 2 cell infiltration STRS was compared with the ADM product in terms of its ability to be infiltrated by cell proliferation. In the case of the ADM product (a representative ADM sample is provided in the H&E staining image in Figure 7), cells were unable to infiltrate the product due to the detailed internal structure of the product itself. However, the STRS product was manufactured with a structure that allowed cells to infiltrate into the construct, and the image on the right side of Figure 7 for in vitro testing confirms this. This indicates that when the product is implanted into an individual, cells can easily infiltrate and self-organize.

[0103] Example 3 Control of Decomposition STRS products may contain natural polymers. In such cases, the degradation period of the natural polymers can be controlled by adjusting the concentration of the crosslinker. STRS products may have similar, higher, or lower degradation resistance compared to ADM, as confirmed by in vitro collagenase degradation testing (Figure 8). This suggests that the physical properties of the product can be adjusted according to the instructions for use of the product.

[0104] Example 4 Manufacturing of STRS A demonstration example of the overall STRS fabrication process is provided. The fabrication process is designed to consider performance factors such as tensile strength and strain, stability such as thermal stability and solvent resistance, and printability (with production printhead speed). Synthetic polymers were investigated according to each detailed factor. Testing of various synthetic polymers resulted in the selection of polycaprolactone and polydioxanone for further characterization. Various pattern design candidates were selected for STRS fabrication, some of which had similar UTS and SUTS values ​​and stress-strain curves similar to those of ADM. As a result of tensile testing using these polymers, a final pattern with a UTS value much lower than that of ADM was selected, which was a pattern with a generally "I"-shaped unit pattern. Following UTS analysis of multiple unit patterns as a function of various line widths, taking into account the scaffold texture, a UTS of 18 ea / cm for PCL was obtained.2 STRS with LW of about 500 μm at a pattern density of 25 ea / cm for PDO 2 A STRS having a LW of 400 μm can be used with a pattern density of 100 μm.

[0105] STRS were fabricated using the inlay method, containing multilayer scaffolds (0.2 mm scaffold × 5 sheets) of the PCL (Pattern P) and PDO (Pattern P) candidate scaffolds described above, respectively. This included tendon decellularized extracellular matrix (dECM) solution as the native polymer and BDDE as the crosslinker. An example of the overall STRS fabrication process is provided in Figure 9.

[0106] 1. Prepare Synthetic Polymer Scaffolds The scaffolds are prepared under the conditions described in the previous section.

[0107] 2. Prepare a mixture of natural polymer and crosslinker a) Tendon dECM is placed in 0.01N HCl at 1.2% w / v and allowed to swell for 4-5 hours at 4°C. b) The swollen tendon dECM is pulverized using a homogenizer. (The grinding conditions were 6000 rpm, and after grinding for 1 minute, the mixture was left on ice for 30 seconds to prevent the temperature from rising. This was repeated a total of 5 times.) c) Store the tendon dECM solution at 4°C prior to use and use within 24 hours. d) The 1.2% tendon dECM solution was diluted with 0.01N HCl containing BDDE to a final concentration of 1 w / v% tendon dECM solution and 0.1 v / v% BDDE. e) Centrifuge the mixture at 2000 rpm for 5 minutes at 4°C to remove any air bubbles in the mixture. f) The mixture is filtered through a 500 μm sieve to remove sub-visible particles. g) Repeat the centrifugation process described in No. 5 to remove air bubbles.

[0108] 3. Combination of natural and synthetic polymers The process involves integrating the prepared scaffold with a mixture of natural polymer and BDDE, as described below. a) Insert the membrane paper into the lower frame b) 5 ml of the prepared mixture is loaded onto the membrane paper. c) Positioning the scaffolds (5 individual sheets) on the loaded mixture. d) Using a scraper, spread the mixture underneath the multi-layer scaffold to fill all the pores of the scaffold. e) Placing membrane paper on top of the multilayer scaffold. f) Assemble the upper frame and remove the remaining mixture. To ensure a uniform thickness of the STRS, the upper frame should be firmly bonded to the lower frame.

[0109] 4. Crosslinking (freeze-drying process) The natural polymers are integrated with the synthetic polymers when crosslinked with BDDE. The natural polymers are crosslinked by the freeze-drying process. a) Samples prepared with a combination of natural and synthetic polymers are placed in a freeze dryer. b) Freeze-drying is carried out under suitable conditions. An example is provided in FIG. 5. Washing This process is for removing residual cross-linking agents after the cross-linking process of natural polymers. a) After freeze-drying is complete, the STRS is separated from the frame. b) Place the tray on the orbital shaker as shown on the right side of the diagram above and place the STRS in it. c) Add 100 ml of distilled water (DW) per STRS. (STRS were based on 75 x 75 mm. For larger sizes, the amount of DW should be adjusted accordingly.) d) Rotate at 30-50 rpm for 10 minutes at room temperature. e) Replace with fresh DW, for a total of 5 rotations and exchanges with fresh DW.

[0110] 6.Lyophilization a) Place the washed STRS into a frame or plasticware and place it into the freeze dryer. b) Lyophilization is carried out under suitable conditions (see, for example, Figure 10). The manufactured STRS product can be packaged and stored or used substantially immediately.

[0111] Example 5 Tensile testing of STRS manufactured from PCL vs. PDO STRS of PCL at a line width of 400 μm and STRS of PDO with a line width of 500 μm, each having a generally "I" shaped unit structure, were characterized for tensile strength.

[0112] Tensile tests were conducted on three types of STRS prototypes made from scaffolds with a line width of 500 μm PCL and 400 μm PDO, and the results can be seen in Table 1. As can be seen from the table, 4.40 MPa was measured for the PCL 500 μm, and each STRS had a lower value than previous synthetic polymer scaffolds. However, as can be seen from Table 2, which shows the results of the ADM tensile test, the PCL 500 μm had a higher strength than MegaDerm and slightly lower strength than XCM.

[0113] [Table 1]

[0114] [Table 2]

[0115] Figure 11 provides UTS images for STRS of different types and line widths compared to MegaDerm. The PCL STRS with a 400 μm line width more closely resembled the ADM control, MegaDerm. Figure 12 provides a bubble chart of STRS and MegaDerm, also reflecting that the PCL STRS with a 400 μm line width more closely resembled the ADM control. PCL STRS or PDO STRS may be further characterized using burst tests, tear tests, cell infiltration assays, etc.

[0116] VII. List of Embodiments Embodiment 1. An artificial support structure comprising one or more biodegradable polymers and one or more extracellular matrix materials, further comprising a plurality of unit patterns, each unit pattern comprising a plurality of filaments arranged continuously, symmetrically, and regularly thereon, each unit pattern constructed with edges of a closed shape, thus forming pores therein, the plurality of unit patterns being connected, thus having intersections with each other, the number of intersections being the same as the number of edges passing through the intersections.

[0117] Embodiment 2. The artificial support structure of embodiment 1, wherein the one or more extracellular matrix materials comprise collagen I.

[0118] Embodiment 3. An artificial support structure according to embodiment 1 or 2, wherein at least one unit pattern has a diameter of about 200 microns to about 3.5 mm.

[0119] Embodiment 4. An artificial support structure according to any one of embodiments 1 to 3, wherein at least one unit pattern has a diameter of about 1.5 mm to about 3 mm.

[0120] Embodiment 5. An artificial support structure according to any one of embodiments 1 to 4, wherein at least one unit pattern has a diameter of about 1.782 mm to about 2.97 mm.

[0121] Embodiment 6. An artificial support structure according to any one of embodiments 1 to 5, wherein the biodegradable polymer material further comprises one or more extracellular matrix materials.

[0122] Embodiment 7. An artificial support structure according to any one of embodiments 1 to 6, wherein the one or more extracellular matrix materials is collagen I.

[0123] Embodiment 8. An artificial support structure according to any one of embodiments 1 to 7, wherein the plurality of connected unit patterns form a substantially planar sheet.

[0124] Embodiment 9. An artificial support structure according to any one of embodiments 1 to 8, wherein a plurality of connected unit patterns form a three-dimensional macrostructure.

[0125] Embodiment 10. The artificial support structure of any one of embodiments 1 to 9, wherein the artificial support structure has a thickness of about 0.5 mm to about 1.5 mm.

[0126] Embodiment 11. The artificial support structure of any one of embodiments 1 to 10, wherein the artificial support structure has a thickness of about 0.7 mm to about 1.3 mm.

[0127] Embodiment 12. The artificial support structure of any one of embodiments 1 to 11, wherein the artificial support structure has a thickness of about 0.9 mm to about 1.1 mm.

[0128] Embodiment 13. The artificial support structure of any one of embodiments 1 to 12, wherein the artificial support structure comprises 1 to 5 layers.

[0129] Embodiment 14. The artificial support structure of embodiment 13, wherein the layer has an additional thickness of 0.10 mm to about 0.3 mm.

[0130] Embodiment 15. The artificial support structure of embodiment 13 or 14, wherein the layer has an additional thickness of 0.15 mm to about 0.25 mm.

[0131] Embodiment 16. The artificial support structure of any of embodiments 13 to 15, wherein the layer has an additional thickness of 0.18 mm to about 0.22 mm.

[0132] Embodiment 17. An artificial support structure according to any one of embodiments 1 to 16, wherein one or more filaments in the plurality of filaments have a diameter of less than 550 microns.

[0133] Embodiment 18. An artificial support structure according to any one of embodiments 1 to 17, wherein one or more filaments in the plurality of filaments have a diameter of less than 500 microns.

[0134] Embodiment 19. An artificial support structure according to any one of embodiments 1 to 18, wherein one or more filaments in the plurality of filaments have a diameter of less than 400 microns.

[0135] Embodiment 20. An artificial support described in any of embodiments 1 to 19, wherein four unit patterns have four intersections with each other and are connected to each other so as to have four edges passing through the four intersections, and the space surrounded by the four unit patterns has the same or similar shape as each unit pattern.

[0136] Embodiment 21. An artificial support according to any one of embodiments 1 to 20, wherein each unit pattern is the capital letter "I" of the English alphabet.

[0137] Embodiment 22. An artificial support as described in embodiment 21, wherein the short edges of the closed shape of each unit pattern have the same length as each other, the long edges have the same length as each other, and the space surrounded by four unit patterns has the same shape as each unit pattern.

[0138] Embodiment 23. The prosthetic support of embodiment 22, wherein in the closed configuration, the ratio of the length of the short edge to the length of the long edge is 1:3.

[0139] Embodiment 24. The artificial support structure of any one of embodiments 1 to 23, wherein the artificial support structure has an ultimate tensile strength of about 4 MPa to about 5 MPa.

[0140] Embodiment 25. The artificial support structure of any one of embodiments 1 to 24, wherein the artificial support structure has an ultimate tensile strength of about 4.05 MPa to about 4.7 MPa.

[0141] Embodiment 26. The artificial support structure of any one of embodiments 1 to 25, wherein the artificial support structure has an ultimate tensile strength of about 4.12 MPa to about 4.50 MPa.

[0142] Embodiment 27. The artificial support structure of any one of embodiments 1 to 26, wherein the artificial support structure has an elastic modulus of about 2.8 MPa to about 4.2 MPa.

[0143] Embodiment 28. The artificial support structure of any one of embodiments 1 to 27, wherein the artificial support structure has an elastic modulus of about 3.00 MPa to about 4.10 MPa.

[0144] Embodiment 29. The artificial support structure of any one of embodiments 1 to 28, wherein the artificial support structure has an elastic modulus of about 3.06 MPa to about 4.00 MPa.

[0145] Embodiment 30. The prosthetic support structure of any one of embodiments 1 to 29, wherein the prosthetic support structure has a suture retention strength of about 20 N to about 26 N.

[0146] Embodiment 31. The prosthetic support structure of any one of embodiments 1 to 30, wherein the prosthetic support structure has a suture retention strength of about 21 N to about 25 N.

[0147] Embodiment 32. The prosthetic support structure of any one of embodiments 1 to 31, wherein the prosthetic support structure has a suture retention strength of about 22.03 N to about 24.27 N.

[0148] Embodiment 33. The artificial support structure of any one of embodiments 1 to 32, wherein the artificial support structure has a burst strength of about 140N to about 170N.

[0149] Embodiment 34. The prosthetic support structure of any one of embodiments 1 to 33, wherein the prosthetic support structure has a burst strength of about 145N to about 163N.

[0150] Embodiment 35. The prosthetic support structure of any one of embodiments 1 to 34, wherein the prosthetic support structure has a burst strength of about 147.14 N to about 161.26 N.

[0151] Embodiment 36. The artificial support structure of any one of embodiments 1 to 35, wherein the artificial support structure has a tear resistance of about 18 N to about 26 N.

[0152] Embodiment 37. The artificial support structure of any one of embodiments 1 to 36, wherein the artificial support structure has a tear resistance of about 19 N to about 25 N.

[0153] Embodiment 38. The artificial support structure of any one of embodiments 1 to 37, wherein the artificial support structure has a tear resistance of about 19.87 N to about 24.92 N.

[0154] Embodiment 39. An artificial support structure comprising one or more biodegradable polymers and one or more extracellular matrix materials, wherein the support structure further comprises a plurality of unit patterns, each unit pattern comprising a plurality of filaments arranged to form symmetrical columns or rows, each unit pattern being constructed with a closed edge, thus forming pores therein, and the columns or rows in which the plurality of unit patterns are repeatedly arranged have Euler paths.

[0155] Embodiment 40. The artificial support structure of embodiment 39, wherein the one or more extracellular matrix materials comprise collagen I.

[0156] Embodiment 41. An artificial support structure described in embodiment 39 or 40, wherein at least one unit pattern has a diameter of about 200 microns to about 3.5 mm.

[0157] Embodiment 42. The artificial support structure of embodiment 41, wherein at least one unit pattern has a diameter of about 1.5 mm to about 3 mm.

[0158] Embodiment 43. The artificial support structure of embodiment 42, wherein at least one unit pattern has a diameter of about 1.782 mm to about 2.97 mm.

[0159] Embodiment 44. An artificial support structure according to any one of embodiments 39 to 43, wherein the biodegradable polymer material further comprises one or more extracellular matrix materials.

[0160] Embodiment 45. An artificial support structure according to any one of embodiments 39 to 44, wherein the one or more extracellular matrix materials is collagen I.

[0161] Embodiment 46. An artificial support structure described in any of embodiments 39 to 45, wherein a plurality of connected unit patterns form a substantially planar sheet.

[0162] Embodiment 47. An artificial support structure according to any one of embodiments 39 to 46, wherein a plurality of connected unit patterns form a three-dimensional macrostructure.

[0163] Embodiment 48. The artificial support structure of any of embodiments 39 to 47, wherein the artificial support structure has a thickness of about 0.5 mm to about 1.5 mm.

[0164] Embodiment 49. The artificial support structure of any one of embodiments 39 to 48, wherein the artificial support structure has a thickness of about 0.7 mm to about 1.3 mm.

[0165] Embodiment 50. The artificial support structure of embodiment 39 or 40, wherein the artificial support structure has a thickness of about 0.9 mm to about 1.1 mm.

[0166] Embodiment 51. The artificial support structure of any one of embodiments 39 to 50, wherein the artificial support structure comprises 1 to 5 layers.

[0167] Embodiment 52. The artificial support structure of embodiment 51, wherein the layer has an additional thickness of 0.10 mm to about 0.3 mm.

[0168] Embodiment 53. The artificial support structure of embodiment 51 or 52, wherein the layer has an additional thickness of 0.15 mm to about 0.25 mm.

[0169] Embodiment 54. The artificial support structure of any of embodiments 51 to 53, wherein the layer has an additional thickness of 0.18 mm to about 0.22 mm.

[0170] Embodiment 55. An artificial support structure described in any of embodiments 39 to 54, wherein one or more filaments in the plurality of filaments have a diameter of less than 550 mm.

[0171] Embodiment 56. An artificial support structure described in any of embodiments 39 to 55, wherein one or more filaments in the plurality of filaments have a diameter of less than 500 mm.

[0172] Embodiment 57. An artificial support structure described in any of embodiments 39 to 56, wherein one or more filaments in the plurality of filaments have a diameter of less than 400 mm.

[0173] Embodiment 58. An artificial support described in any of embodiments 39 to 57, in which a column or row in which multiple unit patterns are repeatedly arranged is connected so that the multiple unit patterns have intersections with multiple unit patterns in an adjacent column or row.

[0174] Embodiment 59. An artificial support as described in embodiment 58, wherein the number of intersections of the multiple unit patterns is the same as the number of edges passing through the intersections.

[0175] Embodiment 60. An artificial support as described in embodiment 59, wherein four adjacent unit patterns have four intersections with each other and are connected to each other so as to have four edges passing through the four intersections, and the space surrounded by the four unit patterns has the same or similar shape as each unit pattern.

[0176] Embodiment 61. An artificial support according to any one of embodiments 39 to 60, wherein each unit pattern is the capital letter "I" of the English alphabet.

[0177] Embodiment 62. An artificial support described in embodiment 61, wherein the short edges of the closed shape of each unit pattern have the same length as each other, the long edges have the same length as each other, and the space surrounded by four unit patterns has the same shape as each unit pattern.

[0178] Embodiment 63. The artificial support of embodiment 62, wherein in the closed configuration, the ratio of the length of the short edge to the length of the long edge is 1:3.

[0179] Embodiment 64. The artificial support of embodiment 63, wherein in the closed shape, the ratio of the length of each short edge to each long edge is 1:3.

[0180] Embodiment 65. An artificial support described in embodiment 64, wherein the multiple unit patterns in the columns or rows in which the multiple unit patterns are repeatedly arranged have an angle of 45° or 135° with respect to the rows or columns.

[0181] Embodiment 66. An artificial support according to embodiment 65, wherein portions of the edges of the multiple unit patterns are regularly arranged to form the edge of the artificial support.

[0182] Embodiment 67. The artificial support structure of any of embodiments 39 to 66, wherein the artificial support has an ultimate tensile strength of about 4.05 MPa to about 4.7 MPa.

[0183] Embodiment 68. The artificial support structure of any of embodiments 39 to 67, wherein the artificial support has an ultimate tensile strength of about 4.12 MPa to about 4.50 MPa.

[0184] Embodiment 69. The artificial support structure of any one of embodiments 39 to 68, wherein the artificial support structure has an elastic modulus of about 2.8 MPa to about 4.2 MPa.

[0185] Embodiment 70. The artificial support structure of any one of embodiments 39 to 69, wherein the artificial support structure has an elastic modulus of about 3.00 MPa to about 4.10 MPa.

[0186] Embodiment 71. The artificial support structure of any one of embodiments 39 to 70, wherein the artificial support structure has an elastic modulus of about 3.06 MPa to about 4.00 MPa.

[0187] Embodiment 72. The artificial support structure of any of embodiments 39 to 71, wherein the artificial support structure has a suture retention strength of about 20 N to about 26 N.

[0188] Embodiment 73. The prosthetic support structure of any of embodiments 39 to 72, wherein the prosthetic support structure has a suture retention strength of about 21 N to about 25 N.

[0189] Embodiment 74. The prosthetic support structure of any of embodiments 39 to 73, wherein the prosthetic support structure has a suture retention strength of about 22.03 N to about 24.27 N.

[0190] Embodiment 75. The artificial support structure of any one of embodiments 39 to 74, wherein the artificial support structure has a burst strength of about 140N to about 170N.

[0191] Embodiment 76. The prosthetic support structure of any one of embodiments 39 to 75, wherein the prosthetic support structure has a burst strength of about 145 N to about 163 N.

[0192] Embodiment 77. The prosthetic support structure of any one of embodiments 39 to 76, wherein the prosthetic support structure has a burst strength of about 147.14 N to about 161.26 N.

[0193] Embodiment 78. The artificial support structure of any of embodiments 39 to 77, wherein the artificial support structure has a tear resistance of about 18 N to about 26 N.

[0194] Embodiment 79. The artificial support structure of any of embodiments 39 to 78, wherein the artificial support structure has a tear resistance of about 19 N to about 25 N.

[0195] Embodiment 80. The artificial support structure of any of embodiments 39 to 79, wherein the artificial support structure has a tear resistance of about 19.87 N to about 24.92 N.

[0196] Embodiment 81. A scaffold comprising a patterned polymeric substrate, the patterned polymeric substrate having thereon a coating of one or more extracellular matrix (ECM) materials, the pattern of the polymeric substrate comprising a series of adjacent rows of unit cell structures each generally shaped like the letter "I", the unit cell structures being aligned within the rows of the patterned polymeric substrate in a vertically alternating pattern of the unit cell structures.

[0197] Embodiment 82. The scaffold of embodiment 81, wherein the series of unit cell structures are further defined as including pores shaped as a centerline, the centerline being longer than two lines of substantially equal length each perpendicular to opposite ends of the centerline, and the alternating pattern is configured such that each end of the centerline of the pore is approximately perpendicular to the centerline of the pore of an adjacent unit cell structure.

[0198] Embodiment 83. A scaffolding as described in embodiment 81 or 82, wherein the scaffolding is configured as one or more sheets, each sheet comprising a first planar side and a second planar side.

[0199] Embodiment 84. A scaffold according to embodiment 83, wherein the scaffold comprises 1, 2, 3, 4, or 5 sheets, or at least 1, 2, 3, 4, or 5 sheets, or no more than 1, 2, 3, 4, or 5 sheets.

[0200] Embodiment 85. A scaffolding described in embodiment 83 or 84, wherein the multiple sheets are configured so that the planar side of one sheet is adjacent to the planar side of another sheet.

[0201] Embodiment 86. A scaffold according to any of embodiments 82 to 85, wherein the scaffold comprises one or more defined shapes.

[0202] Embodiment 87. A scaffold as described in embodiment 86, wherein the defined shape is generally a line, a curve, a circle, a square, a crescent, a triangle, a rectangle, an oval, a trapezoid, or the scaffold includes markings for one or more of the defined shapes.

[0203] Embodiment 88. A scaffold according to any one of embodiments 81 to 87, wherein the polymer substrate comprises polycaprolactone, polydioxanone, or a combination thereof.

[0204] Embodiment 89. A scaffold described in any one of embodiments 81 to 88, wherein the polymer substrate is composed of polycaprolactone.

[0205] Embodiment 90. A scaffold according to any of embodiments 81 to 89, wherein the one or more ECM materials comprise a single type of collagen or a combination of one or more types of collagen.

[0206] Embodiment 91. The scaffold of embodiment 90, wherein the collagen is of tendon, rat tail, bovine, porcine origin, or recombinant.

[0207] Embodiment 92. A scaffold according to embodiment 90 or 91, wherein the combination of one or more types of collagen comprises type I collagen and type III collagen.

[0208] Embodiment 93. The scaffold of embodiment 92, wherein the collagen is telocollagen from bovine tendon, rat tail tendon, or is recombinant.

[0209] Embodiment 94. A scaffolding described in any of embodiments 81 to 93, wherein the coating is included on the first side of the sheet, the second side of the sheet, or both the first and second sides of the sheet.

[0210] Embodiment 95. A scaffold described in any of embodiments 81 to 94, wherein the coating fills the pores of a plurality of unit cell structures of the scaffold.

[0211] Embodiment 96. A scaffold described in any of embodiments 81 to 95, wherein the coating fills the majority of the pores of the unit cell structure of the scaffold.

[0212] Embodiment 97. A scaffold described in any of embodiments 81 to 96, wherein the coating fills the pores of substantially all of the unit cell structure of the scaffold.

[0213] Embodiment 98. A scaffold described in any of embodiments 81 to 97, wherein the coating does not fill the majority of the pores of the unit cell structure of the scaffold.

[0214] Embodiment 99. A scaffold described in any of embodiments 81 to 98, wherein the coating does not fill the pores of substantially all of the unit cell structure of the scaffold.

[0215] Embodiment 100. A scaffold described in any one of embodiments 81 to 99, wherein the thickness of the scaffold is 1 mm or less.

[0216] Embodiment 101. A scaffold according to any of embodiments 81 to 100, wherein the scaffold further comprises one or more therapeutic agents.

[0217] Embodiment 102. The scaffold of embodiment 101, wherein the one or more therapeutic agents comprise one or more growth factors, one or more cytokines, one or more chemokines, one or more drugs, or a combination thereof.

[0218] Embodiment 103. A method for producing a scaffold described in any of embodiments 81 to 102, the method comprising: (a) three-dimensionally printing a patterned polymer substrate; (b) applying one or more ECM materials to the substrate; (c) subjecting the substrate to one or more crosslinking agents; (d) optionally washing the substrate; and (e) subjecting the substrate to conditions of a temperature of less than 15°C, wherein optionally the one or more ECM materials and one or more crosslinking agents are mixed together before being applied to the substrate.

[0219] Embodiment 104. The method of embodiment 103, wherein the polymer substrate is composed of polycaprolactone, polydioxanone, or a combination thereof.

[0220] Embodiment 105. The method of embodiment 103 or 104, wherein applying comprises immersing the substrate in a solution of the coating.

[0221] Embodiment 106. The method of any one of embodiments 103-105, wherein applying comprises placing the substrate over a solution of the coating.

[0222] Embodiment 107. The method of any one of embodiments 103-106, wherein applying comprises spraying, dripping, or depositing the coating onto the substrate.

[0223] Embodiment 108. The method of any one of embodiments 107 to 111, wherein applying is carried out for 1 to 24 hours, 5 to 24 hours, 5 to 20 hours, 8 to 20 hours, 8 to 15 hours, or 9 to 11 hours.

[0224] Embodiment 109. The method of any of embodiments 103-108, wherein the one or more cross-linking agents are selected from the group consisting of 1,4-butanediol diglycidyl ether (BDDE), hexamethylene diisocyanate (HDMI), glutaraldehyde (GA), genipin, and combinations thereof.

[0225] Embodiment 110. The method of any one of embodiments 103-109, wherein (c) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.

[0226] Embodiment 111. The method of any one of embodiments 103 to 110, wherein washing is performed with water.

[0227] Embodiment 112. The method of any one of embodiments 103 to 111, wherein (d) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.

[0228] Embodiment 113. The method of any of embodiments 103-112, wherein (e) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.

[0229] Embodiment 114. The method of any of embodiments 103 to 113, wherein following (e), the produced scaffold is subjected to drying.

[0230] Embodiment 115. The method of any of embodiments 103-114, further comprising applying one or more therapeutic agents to the scaffold.

[0231] Embodiment 116. The method of embodiment 115, wherein one or more therapeutic agents are present in the polymer, the coating, both the polymer and the coating, and / or are applied to at least a portion of the exterior of the scaffold.

[0232] Embodiment 117. The method of any one of embodiments 103-116, wherein the degradation of the patterned polymeric substrate is tunable based on the concentration of the crosslinker.

[0233] Embodiment 118. The method of any one of embodiments 103 to 117, comprising washing the substrate after subjecting the substrate to the one or more crosslinking agents.

[0234] Embodiment 119. The method of any of embodiments 103 to 117, wherein the scaffold is generated in a defined shape.

[0235] Embodiment 120. The method of embodiment 119, wherein the defined shape is a pre-programmed macrostructure that is constructed based on forming with a mandrel or is 3D printed.

[0236] Embodiment 121. A method of reinforcing soft tissue in an individual in need thereof, comprising applying an effective amount of a scaffold according to any of embodiments 1-102 to one or more soft tissue sites of the individual.

[0237] Embodiment 122. The method of embodiment 121, wherein the soft tissue comprises muscle, tendon, ligament, fascia, fat, skin, nerve, blood vessel, or a combination thereof.

[0238] Embodiment 123. The method of embodiment 121 or 122, wherein the soft tissue comprises an injury, a surgical site, a congenital deformity, diseased tissue, or a combination thereof.

[0239] Embodiment 124. The method of any of embodiments 121 to 123, wherein the soft tissue is soft tissue of the breast, stomach, abdomen, groin, leg, arm, hand, face, pelvis, uterus, vagina, penis, cervix, brain, nose, ear, eyelid, heart, kidney, liver, bladder, prostate, larynx, trachea, or combinations thereof.

[0240] Embodiment 125. The method of any of embodiments 121 to 124, wherein the soft tissue comprises breast tissue for breast reconstruction, breast reduction, or breast augmentation.

[0241] Embodiment 126. The method of any one of embodiments 121 to 125, wherein the soft tissue comprises a hernia.

[0242] Embodiment 127. The method of any of embodiments 121-126, wherein applying comprises attaching the scaffold to the individual's soft tissue and / or tissue adjacent to the individual's soft tissue.

[0243] Embodiment 128. The method of embodiment 127, wherein attaching is further defined as the use of suturing, stapling, or surgical adhesive to attach the scaffold to the individual's soft tissue and / or tissue adjacent to the individual's soft tissue.

[0244] Embodiment 129. The method of embodiment 128, wherein the suture is a purse string suture, a running suture, an interrupted suture, a buried suture, a deep suture, or a subcutaneous suture.

[0245] Embodiment 130. The method of embodiment 128 or 129, wherein the suture of the suturing is absorbable.

[0246] Embodiment 131. The method of embodiment 129 or 130, wherein the suture of the suturing is non-absorbable.

[0247] Embodiment 132. A flexible sheet comprising one or more biodegradable polymers and one or more ECM materials, the sheet comprising a plurality of patterned unit cell structures, the plurality of patterned unit cell structures being aligned in adjacent rows of a series of vertically alternating unit cell structures, each of the series of vertically alternating unit cell structures generally comprising a shaped pore having a centerline, the centerline being longer than two substantially equal length lines each perpendicular to opposite ends of the centerline, and the alternating pattern being configured such that each end of the centerline of the pore is approximately perpendicular to the centerline of the pore of an adjacent unit cell structure.

[0248] Embodiment 133. A flexible sheet according to embodiment 132, wherein the unit cell structure is composed of one or more biodegradable polymers.

[0249] Embodiment 134. A flexible sheet according to embodiment 132 or 133, wherein the sheet comprises a coating of one or more ECM materials.

[0250] Embodiment 135. The flexible sheet of embodiment 134, further defined as a unit cell structure comprising one or more coatings of ECM materials.

[0251] Embodiment 136. A flexible sheet according to any one of embodiments 132 to 135, wherein the pores are filled with a coating.

[0252] Embodiment 137. A flexible sheet according to any of embodiments 132 to 136, wherein the one or more ECM materials comprise type I collagen.

[0253] Embodiment 138. A flexible sheet according to any one of embodiments 132 to 137, wherein the sheet is contained in a suitable package.

[0254] All of the methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those skilled in the art that variations can be applied to the methods described herein, and in the steps or sequence of steps of the methods, without departing from the concept, spirit, and scope of the invention. More specifically, it will be apparent that certain agents that are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope, and concept of the disclosed subject matter, as defined by the appended claims.

[0255] [Embodiment] (1) An artificial support structure comprising one or more biodegradable polymers and one or more extracellular matrix materials, the support structure comprising: Further comprising a plurality of unit patterns, each unit pattern including a plurality of filaments arranged continuously, symmetrically, and regularly thereon, each unit pattern being constructed with an edge of a closed shape, thus forming pores therein; An artificial support structure wherein the plurality of unit patterns are connected and therefore have intersections with one another, the number of intersections being the same as the number of edges passing through the intersections. (2) An artificial support structure as described in embodiment 1, wherein the one or more extracellular matrix materials include collagen I. (3) An artificial support structure according to embodiment 1 or 2, wherein at least one unit pattern has a diameter of about 200 μm (about 200 microns) to about 3.5 mm. (4) An artificial support structure according to any one of embodiments 1 to 3, wherein at least one unit pattern has a diameter of about 1.5 mm to about 3 mm. (5) An artificial support structure according to any one of embodiments 1 to 4, wherein at least one unit pattern has a diameter of about 1.782 mm to about 2.97 mm.

[0256] (6) An artificial support structure according to any one of embodiments 1 to 5, wherein the biodegradable polymer material further comprises one or more extracellular matrix materials. (7) An artificial support structure according to any one of embodiments 1 to 6, wherein the one or more extracellular matrix materials is collagen I. (8) The artificial support structure according to any one of embodiments 1 to 7, wherein the plurality of connected unit patterns form a substantially planar sheet. (9) The artificial support structure according to any one of embodiments 1 to 8, wherein the plurality of connected unit patterns form a three-dimensional macrostructure. (10) The artificial support structure according to any one of embodiments 1 to 9, wherein the artificial support structure has a thickness of about 0.5 mm to about 1.5 mm.

[0257] (11) The artificial support structure according to any one of embodiments 1 to 10, wherein the artificial support structure has a thickness of about 0.7 mm to about 1.3 mm. (12) The artificial support structure according to any one of embodiments 1 to 11, wherein the artificial support structure has a thickness of about 0.9 mm to about 1.1 mm. (13) The artificial support structure of any one of embodiments 1 to 12, wherein the artificial support structure comprises 1 to 5 layers. (14) The artificial support structure of embodiment 13, wherein the layer has an additional thickness of 0.10 mm to about 0.3 mm. (15) The artificial support structure of embodiment 13 or 14, wherein the layer has an additional thickness of 0.15 mm to about 0.25 mm.

[0258] (16) The artificial support structure of any one of embodiments 13 to 15, wherein the layer has an additional thickness of 0.18 mm to about 0.22 mm. (17) The artificial support structure of any one of embodiments 1 to 16, wherein one or more filaments in the plurality of filaments have a diameter of less than 550 μm (550 microns). (18) The artificial support structure of any one of embodiments 1 to 17, wherein one or more filaments in the plurality of filaments have a diameter of less than 500 μm (500 microns). (19) The artificial support structure of any one of embodiments 1 to 18, wherein one or more filaments in the plurality of filaments have a diameter of less than 400 μm (400 microns). (20) An artificial support according to any one of embodiments 1 to 19, wherein four unit patterns have four intersections with each other and are connected to each other so as to have four edges passing through the four intersections, and the space surrounded by the four unit patterns has the same or similar shape as each unit pattern.

[0259] (21) The artificial support according to any one of embodiments 1 to 20, wherein each unit pattern is the capital letter "I" of the English alphabet. (22) An artificial support according to embodiment 21, wherein the short edges of the closed shape of each unit pattern have the same length as each other, the long edges of the closed shape of each unit pattern have the same length as each other, and the space surrounded by the four unit patterns has the same shape as each unit pattern. (23) The artificial support of embodiment 22, wherein in the closed configuration, the ratio of the length of the short edge to the length of the long edge is 1:3. (24) The artificial support structure of any one of embodiments 1 to 23, wherein the artificial support structure has an ultimate tensile strength of about 4 MPa to about 5 MPa. (25) The artificial support structure of any one of embodiments 1 to 24, wherein the artificial support structure has an ultimate tensile strength of about 4.05 MPa to about 4.7 MPa.

[0260] (26) The artificial support structure of any one of embodiments 1 to 25, wherein the artificial support structure has an ultimate tensile strength of about 4.12 MPa to about 4.50 MPa. (27) The artificial support structure according to any one of embodiments 1 to 26, wherein the artificial support structure has an elastic modulus of about 2.8 MPa to about 4.2 MPa. (28) The artificial support structure according to any one of embodiments 1 to 27, wherein the artificial support structure has an elastic modulus of about 3.00 MPa to about 4.10 MPa. (29) The artificial support structure of any one of embodiments 1 to 28, wherein the artificial support structure has an elastic modulus of about 3.06 MPa to about 4.00 MPa. (30) The artificial support structure according to any one of embodiments 1 to 29, wherein the artificial support structure has a suture retention strength of about 20 N to about 26 N.

[0261] (31) The artificial support structure according to any one of embodiments 1 to 30, wherein the artificial support structure has a suture retention strength of about 21 N to about 25 N. (32) The artificial support structure of any one of embodiments 1 to 31, wherein the artificial support structure has a suture retention strength of about 22.03 N to about 24.27 N. (33) The artificial support structure of any one of embodiments 1 to 32, wherein the artificial support structure has a burst strength of about 140N to about 170N. (34) The artificial support structure of any one of embodiments 1 to 33, wherein the artificial support structure has a burst strength of about 145 N to about 163 N. (35) The artificial support structure of any one of embodiments 1 to 34, wherein the artificial support structure has a burst strength of about 147.14 N to about 161.26 N.

[0262] (36) The artificial support structure of any one of embodiments 1 to 35, wherein the artificial support structure has a tear resistance of about 18 N to about 26 N. (37) The artificial support structure of any one of embodiments 1 to 36, wherein the artificial support structure has a tear resistance of about 19 N to about 25 N. (38) The artificial support structure of any one of embodiments 1 to 37, wherein the artificial support structure has a tear resistance of about 19.87 N to about 24.92 N. (39) An artificial support structure comprising one or more biodegradable polymers and one or more extracellular matrix materials, the support structure comprising: Further comprising a plurality of unit patterns, each unit pattern including a plurality of filaments repeatedly arranged to form mutually symmetrical rows or columns, each unit pattern being constructed with an edge of a closed shape, thus forming pores therein; The artificial support structure, wherein the column or the row in which the plurality of unit patterns are repeatedly arranged has an Euler path. (40) The artificial support structure described in embodiment 39, wherein the one or more extracellular matrix materials include collagen I.

[0263] (41) The artificial support structure of embodiment 39 or 40, wherein at least one unit pattern has a diameter of about 200 μm (about 200 microns) to about 3.5 mm. (42) The artificial support structure of embodiment 41, wherein at least one unit pattern has a diameter of about 1.5 mm to about 3 mm. (43) The artificial support structure of embodiment 42, wherein at least one unit pattern has a diameter of about 1.782 mm to about 2.97 mm. (44) An artificial support structure according to any one of embodiments 39 to 43, wherein the biodegradable polymer material further comprises one or more extracellular matrix materials. (45) An artificial support structure according to any one of embodiments 39 to 44, wherein the one or more extracellular matrix materials is collagen I.

[0264] (46) An artificial support structure according to any one of embodiments 39 to 45, wherein the plurality of connected unit patterns form a substantially planar sheet. (47) The artificial support structure according to any one of embodiments 39 to 46, wherein the plurality of connected unit patterns form a three-dimensional macrostructure. (48) The artificial support structure of any one of embodiments 39 to 47, wherein the artificial support structure has a thickness of about 0.5 mm to about 1.5 mm. (49) The artificial support structure of any one of embodiments 39 to 48, wherein the artificial support structure has a thickness of about 0.7 mm to about 1.3 mm. (50) The artificial support structure of embodiment 39 or 40, wherein the artificial support structure has a thickness of about 0.9 mm to about 1.1 mm.

[0265] (51) The artificial support structure of any one of embodiments 39 to 50, wherein the artificial support structure comprises 1 to 5 layers. (52) The artificial support structure of embodiment 51, wherein the layer has an additional thickness of 0.10 mm to about 0.3 mm. (53) The artificial support structure of embodiment 51 or 52, wherein the layer has an additional thickness of 0.15 mm to about 0.25 mm. (54) The artificial support structure of any one of embodiments 51 to 53, wherein the layer has an additional thickness of 0.18 mm to about 0.22 mm. (55) The artificial support structure of any one of embodiments 39 to 54, wherein one or more filaments in the plurality of filaments have a diameter of less than 550 mm.

[0266] (56) The artificial support structure of any one of embodiments 39 to 55, wherein one or more filaments in the plurality of filaments have a diameter of less than 500 mm. (57) The artificial support structure of any one of embodiments 39 to 56, wherein one or more filaments in the plurality of filaments have a diameter of less than 400 mm. (58) An artificial support described in any of embodiments 39 to 57, wherein the columns or rows in which the multiple unit patterns are repeatedly arranged are connected so that the multiple unit patterns have intersections with the multiple unit patterns in adjacent columns or rows. (59) The artificial support described in embodiment 58, wherein the number of intersections of the multiple unit patterns is the same as the number of edges passing through the intersections. (60) The artificial support described in embodiment 59, wherein four adjacent unit patterns have four intersections with each other and are connected to each other so as to have four edges passing through the four intersections, and the space surrounded by the four unit patterns has the same or similar shape as each unit pattern.

[0267] (61) The artificial support according to any one of embodiments 39 to 60, wherein each unit pattern is the capital letter "I" of the English alphabet. (62) An artificial support as described in embodiment 61, wherein the short edges of the closed shape of each unit pattern have the same length as each other, the long edges have the same length as each other, and the space surrounded by the four unit patterns has the same shape as each unit pattern. (63) The artificial support of embodiment 62, wherein in the closed shape, the ratio of the length of the short edge to the length of the long edge is 1:3. (64) The artificial support of embodiment 63, wherein in the closed shape, the ratio of the length of each short edge to each long edge is 1:3. (65) An artificial support as described in embodiment 64, wherein the plurality of unit patterns in the column or row in which the plurality of unit patterns are repeatedly arranged have an angle of 45° or 135° with respect to the row or column.

[0268] (66) An artificial support according to embodiment 65, wherein a portion of the edge of the plurality of unit patterns is regularly arranged to form the edge of the artificial support. (67) The artificial support structure of any one of embodiments 39 to 66, wherein the artificial support has an ultimate tensile strength of about 4.05 MPa to about 4.7 MPa. (68) The artificial support structure of any one of embodiments 39 to 67, wherein the artificial support has an ultimate tensile strength of about 4.12 MPa to about 4.50 MPa. (69) The artificial support structure of any one of embodiments 39 to 68, wherein the artificial support structure has an elastic modulus of about 2.8 MPa to about 4.2 MPa. (70) The artificial support structure of any one of embodiments 39 to 69, wherein the artificial support structure has an elastic modulus of about 3.00 MPa to about 4.10 MPa.

[0269] (71) The artificial support structure of any one of embodiments 39 to 70, wherein the artificial support structure has an elastic modulus of about 3.06 MPa to about 4.00 MPa. (72) The artificial support structure of any one of embodiments 39 to 71, wherein the artificial support structure has a suture retention strength of about 20 N to about 26 N. (73) The artificial support structure of any one of embodiments 39 to 72, wherein the artificial support structure has a suture retention strength of about 21 N to about 25 N. (74) The artificial support structure of any one of embodiments 39 to 73, wherein the artificial support structure has a suture retention strength of about 22.03 N to about 24.27 N. (75) The artificial support structure of any one of embodiments 39 to 74, wherein the artificial support structure has a burst strength of about 140 N to about 170 N.

[0270] (76) The artificial support structure of any one of embodiments 39 to 75, wherein the artificial support structure has a burst strength of about 145 N to about 163 N. (77) The artificial support structure of any one of embodiments 39 to 76, wherein the artificial support structure has a burst strength of about 147.14 N to about 161.26 N. (78) The artificial support structure of any one of embodiments 39 to 77, wherein the artificial support structure has a tear resistance of about 18 N to about 26 N. (79) The artificial support structure of any one of embodiments 39 to 78, wherein the artificial support structure has a tear resistance of about 19 N to about 25 N. (80) The artificial support structure of any one of embodiments 39 to 79, wherein the artificial support structure has a tear resistance of about 19.87 N to about 24.92 N.

[0271] (81) A scaffold comprising a patterned polymeric substrate having thereon a coating of one or more extracellular matrix (ECM) materials, wherein the pattern of the polymeric substrate comprises a series of adjacent rows of unit cell structures, each generally shaped like the letter "I," and wherein the unit cell structures are aligned within the rows of the patterned polymeric substrate in a vertically alternating pattern of the unit cell structures. (82) The scaffold of embodiment 81, wherein the series of unit cell structures are further defined as including pores shaped as centerlines, the centerlines being longer than two lines of substantially equal length each perpendicular to opposite ends of the centerline, and the alternating pattern is configured such that each of the ends of the centerline of a pore is approximately perpendicular to the centerline of a pore of an adjacent unit cell structure. (83) The scaffolding of embodiment 81 or 82, wherein the scaffolding is configured as one or more sheets, each of the sheets including a first planar side and a second planar side. (84) The scaffold of embodiment 83, wherein the scaffold comprises 1, 2, 3, 4, or 5 sheets, or at least 1, 2, 3, 4, or 5 sheets, or no more than 1, 2, 3, 4, or 5 sheets. (85) A scaffolding as described in embodiment 83 or 84, wherein the multiple sheets are configured so that a planar side of one sheet is adjacent to a planar side of another sheet.

[0272] (86) The scaffold described in any one of embodiments 82 to 85, wherein the scaffold comprises one or more defined shapes. (87) The scaffold of embodiment 86, wherein the defined shape is generally a line, a curve, a circle, a square, a crescent, a triangle, a rectangle, an oval, a trapezoid, or the scaffold includes markings for one or more of the defined shapes. (88) The scaffolding of any one of embodiments 81 to 87, wherein the polymer matrix comprises polycaprolactone, polydioxanone, or a combination thereof. (89) The scaffold of any one of embodiments 81 to 88, wherein the polymer substrate is composed of polycaprolactone. (90) A scaffold described in any of embodiments 81 to 89, wherein the one or more ECM materials comprise a single type of collagen or a combination of one or more types of collagen.

[0273] (91) The scaffold of embodiment 90, wherein the collagen is derived from tendon, rat tail, bovine, porcine, or recombinant. (92) The scaffold described in embodiment 90 or 91, wherein the combination of one or more types of collagen comprises type I collagen and type III collagen. (93) The scaffold of embodiment 92, wherein the collagen is telocollagen from bovine tendon, rat tail tendon, or recombinant. (94) The scaffolding of any one of embodiments 81 to 93, wherein the coating is included on the first side of the sheet, the second side of the sheet, or both the first side and the second side of the sheet. (95) A scaffold described in any one of embodiments 81 to 94, wherein the coating fills the pores of a plurality of unit cell structures of the scaffold.

[0274] (96) A scaffold described in any one of embodiments 81 to 95, wherein the coating fills the pores of the majority of the unit cell structure of the scaffold. (97) The scaffold described in any one of embodiments 81 to 96, wherein the coating fills the pores of substantially all unit cell structures of the scaffold. (98) A scaffold described in any one of embodiments 81 to 97, wherein the coating does not fill the majority of the pores in the unit cell structure of the scaffold. (99) The scaffold described in any one of embodiments 81 to 98, wherein the coating does not fill the pores of substantially all unit cell structures of the scaffold. (100) A scaffold according to any one of embodiments 81 to 99, wherein the thickness of the scaffold is 1 mm or less.

[0275] (101) The scaffold described in any one of embodiments 81 to 100, wherein the scaffold further comprises one or more therapeutic agents. (102) The scaffold of embodiment 101, wherein the one or more therapeutic agents comprise one or more growth factors, one or more cytokines, one or more chemokines, one or more drugs, or a combination thereof. (103) A method for producing a scaffold according to any one of embodiments 81 to 102, said method comprising: (a) three-dimensionally printing the patterned polymer substrate; (b) applying the one or more ECM materials to the substrate; (c) subjecting the substrate to one or more cross-linking agents; (d) optionally cleaning the substrate; (e) subjecting the substrate to a temperature condition of less than 15°C, optionally wherein the one or more ECM materials and the one or more crosslinking agents are mixed together before being applied to the substrate. (104) The method of embodiment 103, wherein the polymer substrate is composed of polycaprolactone, polydioxanone, or a combination thereof. 105. The method of claim 103 or 104, wherein the applying comprises immersing the substrate in a solution of the coating.

[0276] (106) The method of any one of embodiments 103 to 105, wherein the applying comprises placing the substrate over a solution of the coating. (107) The method of any one of embodiments 103 to 106, wherein the applying comprises spraying, dripping, or depositing the coating onto the substrate. (108) The method of any one of embodiments 107 to 111, wherein the applying is carried out for 1 to 24 hours, 5 to 24 hours, 5 to 20 hours, 8 to 20 hours, 8 to 15 hours, or 9 to 11 hours. (109) The method of any one of embodiments 103 to 108, wherein the one or more crosslinking agents are selected from the group consisting of 1,4-butanediol diglycidyl ether (BDDE), hexamethylene diisocyanate (HDMI), glutaraldehyde (GA), genipin, and combinations thereof. (110) The method of any one of embodiments 103 to 109, wherein (c) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.

[0277] (111) The method of any one of embodiments 103 to 110, wherein the washing is performed with water. (112) The method of any one of embodiments 103 to 111, wherein (d) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours. (113) The method of any one of embodiments 103 to 112, wherein (e) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours. (114) The method of any one of embodiments 103 to 113, wherein following (e), the generated scaffold is subjected to drying. (115) The method of any one of embodiments 103 to 114, further comprising applying one or more therapeutic agents to the scaffold.

[0278] (116) The method of embodiment 115, wherein the one or more therapeutic agents are present in the polymer, the coating, both the polymer and the coating, and / or are applied to at least a portion of the exterior of the scaffold. (117) The method of any one of embodiments 103 to 116, wherein the degradation of the patterned polymeric substrate is tunable based on the concentration of the crosslinker. (118) The method of any one of embodiments 103 to 117, comprising washing the substrate after subjecting the substrate to one or more crosslinking agents. (119) The method of any one of embodiments 103 to 117, wherein the scaffold is produced in a defined shape. (120) The method of embodiment 119, wherein the defined shape is a pre-programmed macrostructure that is constructed based on forming with a mandrel or that is 3D printed.

[0279] (121) A method for reinforcing soft tissue in an individual in need thereof, comprising applying an effective amount of a scaffold according to any of embodiments 1 to 102 to one or more soft tissue sites of the individual. (122) The method of embodiment 121, wherein the soft tissue comprises muscle, tendon, ligament, fascia, fat, skin, nerve, blood vessel, or a combination thereof. (123) The method of embodiment 121 or 122, wherein the soft tissue comprises an injury, a surgical site, a congenital deformity, diseased tissue, or a combination thereof. (124) The method of any one of embodiments 121 to 123, wherein the soft tissue is soft tissue of the breast, stomach, abdomen, groin, leg, arm, hand, face, pelvis, uterus, vagina, penis, cervix, brain, nose, ear, eyelid, heart, kidney, liver, bladder, prostate, larynx, trachea, or a combination thereof. (125) The method of any one of embodiments 121 to 124, wherein the soft tissue comprises breast tissue for breast reconstruction, breast reduction, or breast augmentation.

[0280] (126) The method of any one of embodiments 121 to 125, wherein the soft tissue comprises a hernia. (127) The method of any of embodiments 121 to 126, wherein the applying step comprises attaching the scaffold to the soft tissue of the individual and / or tissue adjacent to the soft tissue of the individual. (128) The method of embodiment 127, wherein said attaching is further defined as the use of suturing, stapling, or surgical adhesive to attach the scaffold to the soft tissue of the individual and / or tissue adjacent to the soft tissue of the individual. (129) The method of embodiment 128, wherein the suture is a purse string suture, a running suture, an interrupted suture, a buried suture, a deep suture, or a subcutaneous suture. (130) The method of embodiment 128 or 129, wherein the suture of the suture is absorbable.

[0281] (131) The method of embodiment 129 or 130, wherein the suture of the suture is non-absorbable. (132) A flexible sheet comprising one or more biodegradable polymers and one or more ECM materials, the sheet comprising a plurality of patterned unit cell structures, the plurality of patterned unit cell structures aligned in adjacent rows of a series of vertically alternating unit cell structures, each of the series of vertically alternating unit cell structures generally comprising a shaped pore having a centerline, the centerline being longer than two substantially equal length lines each perpendicular to opposite ends of the centerline, the alternating pattern configured such that each of the ends of the centerline of a pore is approximately perpendicular to the centerline of a pore of an adjacent unit cell structure. (133) The flexible sheet of embodiment 132, wherein the unit cell structure is composed of one or more biodegradable polymers. (134) The flexible sheet of embodiment 132 or 133, wherein the sheet comprises a coating of one or more ECM materials. (135) The flexible sheet of embodiment 134, further defined as the unit cell structure comprising a coating of one or more ECM materials.

[0282] (136) The flexible sheet of any one of embodiments 132 to 135, wherein the pores are filled with the coating. (137) A flexible sheet described in any of embodiments 132 to 136, wherein the one or more ECM materials include type I collagen. (138) The flexible sheet of any one of embodiments 132 to 137, wherein the sheet is contained in a suitable package.

Claims

1. 1. An artificial support structure comprising one or more biodegradable polymers and one or more extracellular matrix materials, said support structure comprising: Further comprising a plurality of unit patterns, each unit pattern including a plurality of filaments arranged continuously, symmetrically, and regularly thereon, each unit pattern being constructed with an edge of a closed shape, thus forming pores therein; An artificial support structure wherein the plurality of unit patterns are connected and therefore have intersections with one another, the number of intersections being the same as the number of edges passing through the intersections.

2. The artificial support structure of claim 1 , wherein the one or more extracellular matrix materials comprise collagen I.

3. The artificial support structure of claim 1 or 2, wherein at least one unit pattern has a diameter of about 200 μm (about 200 microns) to about 3.5 mm.

4. The artificial support structure of claim 1, wherein at least one unit pattern has a diameter of about 1.5 mm to about 3 mm.

5. The artificial support structure of claim 1, wherein at least one unit pattern has a diameter of about 1.782 mm to about 2.97 mm.

6. The artificial support structure of claim 1 , wherein the biodegradable polymeric material further comprises one or more extracellular matrix materials.

7. The artificial support structure of claim 1 , wherein the one or more extracellular matrix materials is collagen I.

8. The artificial support structure of claim 1 , wherein the plurality of connected unit patterns form a substantially planar sheet.

9. The artificial support structure of claim 1 , wherein the plurality of connected unit patterns form a three-dimensional macrostructure.

10. The prosthetic support structure of claim 1, wherein the prosthetic support structure has a thickness of about 0.5 mm to about 1.5 mm.

11. The prosthetic support structure of claim 1, wherein the prosthetic support structure has a thickness of about 0.7 mm to about 1.3 mm.

12. The prosthetic support structure of claim 1 , wherein the prosthetic support structure has a thickness of about 0.9 mm to about 1.1 mm.

13. The prosthetic support structure of claim 1, wherein the prosthetic support structure comprises 1 to 5 layers.

14. The artificial support structure of claim 13, wherein the layer has an additional thickness of from 0.10 mm to about 0.3 mm.

15. The artificial support structure of claim 13 or 14, wherein the layer has an additional thickness of from 0.15 mm to about 0.25 mm.

16. The artificial support structure of claim 13, wherein the layer has an additional thickness of from 0.18 mm to about 0.22 mm.

17. The prosthetic support structure of claim 1 , wherein one or more filaments in the plurality of filaments have a diameter of less than 550 μm (550 microns).

18. The prosthetic support structure of claim 1 , wherein one or more filaments in the plurality of filaments have a diameter of less than 500 μm (500 microns).

19. The prosthetic support structure of claim 1 , wherein one or more filaments in the plurality of filaments have a diameter of less than 400 μm (400 microns).

20. The artificial support described in claim 1, wherein four unit patterns have four intersections with each other and are connected to each other so as to have four edges passing through the four intersections, and a space surrounded by the four unit patterns has the same or similar shape as each unit pattern.

21. The artificial support of claim 1 , wherein each unit pattern is a capital letter "I" of the English alphabet.

22. The artificial support of claim 21 , wherein the short edges of the closed shape of each unit pattern have the same length as each other, the long edges of the closed shape of each unit pattern have the same length as each other, and the space surrounded by the four unit patterns has the same shape as each unit pattern.

23. 23. The prosthetic support of claim 22, wherein in the closed configuration, the ratio of the length of the short edge to the length of the long edge is 1:

3.

24. The prosthetic support structure of claim 1, wherein the prosthetic support structure has an ultimate tensile strength of about 4 MPa to about 5 MPa.

25. The prosthetic support structure of claim 1, wherein the prosthetic support structure has an ultimate tensile strength of about 4.05 MPa to about 4.7 MPa.

26. The prosthetic support structure of claim 1, wherein the prosthetic support structure has an ultimate tensile strength of about 4.12 MPa to about 4.50 MPa.

27. The artificial support structure of claim 1, wherein the artificial support structure has an elastic modulus of about 2.8 MPa to about 4.2 MPa.

28. The prosthetic support structure of claim 1, wherein the prosthetic support structure has a modulus of elasticity of about 3.00 MPa to about 4.10 MPa.

29. The prosthetic support structure of claim 1, wherein the prosthetic support structure has a modulus of elasticity of about 3.06 MPa to about 4.00 MPa.

30. The prosthetic support structure of claim 1 , wherein the prosthetic support structure has a suture retention strength of about 20N to about 26N.

31. The prosthetic support structure of claim 1 , wherein the prosthetic support structure has a suture retention strength of about 21 N to about 25 N.

32. The prosthetic support structure of claim 1 , wherein the prosthetic support structure has a suture retention strength of about 22.03 N to about 24.27 N.

33. The prosthetic support structure of claim 1 , wherein the prosthetic support structure has a burst strength of about 140N to about 170N.

34. The prosthetic support structure of claim 1 , wherein the prosthetic support structure has a burst strength of about 145N to about 163N.

35. The prosthetic support structure of claim 1 , wherein the prosthetic support structure has a burst strength of about 147.14 N to about 161.26 N.

36. The prosthetic support structure of claim 1 , wherein the prosthetic support structure has a tear resistance of about 18N to about 26N.

37. The prosthetic support structure of claim 1 , wherein the prosthetic support structure has a tear resistance of about 19N to about 25N.

38. The prosthetic support structure of claim 1 , wherein the prosthetic support structure has a tear resistance of about 19.87 N to about 24.92 N.

39. 1. An artificial support structure comprising one or more biodegradable polymers and one or more extracellular matrix materials, said support structure comprising: Further comprising a plurality of unit patterns, each unit pattern including a plurality of filaments repeatedly arranged to form mutually symmetrical rows or columns, each unit pattern being constructed with an edge of a closed shape, thus forming pores therein; The artificial support structure, wherein the column or the row in which the plurality of unit patterns are repeatedly arranged has an Euler path.

40. 40. The artificial support structure of claim 39, wherein the one or more extracellular matrix materials comprise collagen I.

41. The artificial support structure of claim 39 or 40, wherein at least one unit pattern has a diameter of about 200 μm (about 200 microns) to about 3.5 mm.

42. The artificial support structure of claim 41, wherein at least one unit pattern has a diameter of about 1.5 mm to about 3 mm.

43. The artificial support structure of claim 42, wherein at least one unit pattern has a diameter of about 1.782 mm to about 2.97 mm.

44. 40. The artificial support structure of claim 39, wherein the biodegradable polymeric material further comprises one or more extracellular matrix materials.

45. 40. The artificial support structure of claim 39, wherein the one or more extracellular matrix materials is collagen I.

46. The prosthetic support structure of claim 39, wherein the plurality of connected unit patterns form a substantially planar sheet.

47. The artificial support structure of claim 39, wherein the plurality of connected unit patterns form a three-dimensional macrostructure.

48. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a thickness of about 0.5 mm to about 1.5 mm.

49. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a thickness of about 0.7 mm to about 1.3 mm.

50. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a thickness of about 0.9 mm to about 1.1 mm.

51. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure comprises 1 to 5 layers.

52. 52. The artificial support structure of claim 51, wherein the layer has an additional thickness of from 0.10 mm to about 0.3 mm.

53. 52. The artificial support structure of claim 51, wherein the layer has an additional thickness of from 0.15 mm to about 0.25 mm.

54. 52. The artificial support structure of claim 51, wherein the layer has an additional thickness of from 0.18 mm to about 0.22 mm.

55. 40. The prosthetic support structure of claim 39, wherein one or more filaments in the plurality of filaments have a diameter of less than 550 mm.

56. 40. The prosthetic support structure of claim 39, wherein one or more filaments in the plurality of filaments have a diameter of less than 500 mm.

57. 40. The prosthetic support structure of claim 39, wherein one or more filaments in the plurality of filaments have a diameter of less than 400 mm.

58. The artificial support described in claim 39, wherein the columns or rows in which the multiple unit patterns are repeatedly arranged are connected so that the multiple unit patterns have intersections with the multiple unit patterns in adjacent columns or rows.

59. 59. The artificial support of claim 58, wherein the number of intersections in the plurality of unit patterns is equal to the number of edges passing through the intersections.

60. The artificial support described in claim 59, wherein four adjacent unit patterns have four intersections with each other and are connected to each other so as to have four edges passing through the four intersections, and a space surrounded by the four unit patterns has the same or similar shape as each unit pattern.

61. The artificial support of claim 39 , wherein each unit pattern is a capital letter “I” of the English alphabet.

62. The artificial support described in claim 61, wherein the short edges of the closed shape of each unit pattern have the same length as each other, the long edges have the same length as each other, and the space surrounded by the four unit patterns has the same shape as each unit pattern.

63. 63. The prosthetic support of claim 62, wherein in the closed configuration, the ratio of the length of the short edge to the length of the long edge is 1:

3.

64. 64. The prosthetic support of claim 63, wherein in the closed configuration, the ratio of the length of each short edge to each long edge is 1:

3.

65. The artificial support of claim 64, wherein the plurality of unit patterns in the column or row in which the plurality of unit patterns are repeatedly arranged have an angle of 45° or 135° with respect to the row or column.

66. The artificial support according to claim 65, wherein a portion of the edges of the plurality of unit patterns are regularly arranged to form the edge of the artificial support.

67. 40. The prosthetic support structure of claim 39, wherein the prosthetic support has an ultimate tensile strength of about 4.05 MPa to about 4.7 MPa.

68. 40. The prosthetic support structure of claim 39, wherein the prosthetic support has an ultimate tensile strength of about 4.12 MPa to about 4.50 MPa.

69. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a modulus of elasticity of about 2.8 MPa to about 4.2 MPa.

70. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a modulus of elasticity of about 3.00 MPa to about 4.10 MPa.

71. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a modulus of elasticity of about 3.06 MPa to about 4.00 MPa.

72. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a suture retention strength of about 20N to about 26N.

73. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a suture retention strength of about 21N to about 25N.

74. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a suture retention strength of about 22.03 N to about 24.27 N.

75. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a burst strength of about 140N to about 170N.

76. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a burst strength of about 145N to about 163N.

77. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a burst strength of about 147.14 N to about 161.26 N.

78. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a tear resistance of about 18N to about 26N.

79. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a tear resistance of about 19N to about 25N.

80. 40. The prosthetic support structure of claim 39, wherein the prosthetic support structure has a tear resistance of about 19.87 N to about 24.92 N.

81. 1. A scaffold comprising a patterned polymeric substrate having thereon a coating of one or more extracellular matrix (ECM) materials, wherein the pattern of the polymeric substrate comprises a series of adjacent rows of unit cell structures, each generally shaped like the letter "I," and wherein the unit cell structures are aligned within the rows of the patterned polymeric substrate in a vertically alternating pattern of the unit cell structures.

82. 82. The scaffolding of claim 81, wherein said series of said unit cell structures is further defined as including a pore shaped as a centerline, said centerline having a length greater than two lines of substantially equal length each perpendicular to opposite ends of said centerline, and said alternating pattern is configured such that each of said ends of said centerline of a pore is approximately perpendicular to the centerline of a pore of an adjacent unit cell structure.

83. 83. The scaffolding of claim 81 or 82, wherein the scaffolding is configured as one or more sheets, each of the sheets comprising a first planar side and a second planar side.

84. 84. The scaffolding of claim 83, wherein the scaffolding comprises 1, 2, 3, 4, or 5 sheets, or alternatively comprises at least 1, 2, 3, 4, or 5 sheets or no more than 1, 2, 3, 4, or 5 sheets.

85. 84. The scaffolding of claim 83, wherein the plurality of sheets are configured such that a planar side of one sheet is adjacent a planar side of another sheet.

86. 83. The scaffold of claim 82, wherein the scaffold comprises one or more defined shapes.

87. 87. The scaffolding of claim 86, wherein the defined shape is generally a line, a curve, a circle, a square, a crescent, a triangle, a rectangle, an oval, a trapezoid, or the scaffolding includes markings for one or more of the defined shapes.

88. 82. The scaffolding of claim 81 , wherein the polymeric matrix comprises polycaprolactone, polydioxanone, or a combination thereof.

89. 82. The scaffolding of claim 81 , wherein said polymer matrix is ​​composed of polycaprolactone.

90. 82. The scaffold of claim 81, wherein the one or more ECM materials comprise a single type of collagen or a combination of one or more types of collagen.

91. 91. The scaffold of claim 90, wherein the collagen is derived from tendon, rat tail, bovine, porcine or is recombinant.

92. 92. The scaffold of claim 90 or 91, wherein the combination of one or more types of collagen comprises type I collagen and type III collagen.

93. 93. The scaffold of claim 92, wherein the collagen is telocollagen from bovine tendon, rat tail tendon, or is recombinant.

94. 82. The scaffolding of claim 81 , wherein the coating is included on the first side of the sheet, the second side of the sheet, or both the first side and the second side of the sheet.

95. 82. The scaffold of claim 81, wherein said coating fills said pores of a plurality of unit cell structures of said scaffold.

96. 82. The scaffold of claim 81, wherein said coating fills the majority of said pores of said scaffold unit cell structure.

97. 82. The scaffold of claim 81, wherein said coating fills said pores of substantially all unit cell structures of said scaffold.

98. 82. The scaffold of claim 81, wherein said coating does not fill the majority of said pores of said scaffold unit cell structure.

99. 82. The scaffold of claim 81, wherein said coating does not fill said pores of substantially all unit cell structures of said scaffold.

100. 82. The scaffold of claim 81, wherein the thickness of the scaffold is 1 mm or less.

101. 82. The scaffold of claim 81, wherein the scaffold further comprises one or more therapeutic agents.

102. 102. The scaffold of claim 101, wherein the one or more therapeutic agents comprise one or more growth factors, one or more cytokines, one or more chemokines, one or more drugs, or a combination thereof.

103. 82. A method of producing a scaffold according to claim 81, said method comprising: (a) three-dimensionally printing the patterned polymer substrate; (b) applying the one or more ECM materials to the substrate; (c) subjecting the substrate to one or more cross-linking agents; (d) optionally cleaning the substrate; (e) subjecting the substrate to a temperature condition of less than 15°C, optionally wherein the one or more ECM materials and the one or more crosslinking agents are mixed together before being applied to the substrate.

104. 104. The method of claim 103, wherein the polymeric substrate is composed of polycaprolactone, polydioxanone, or a combination thereof.

105. 105. The method of claim 103 or 104, wherein the applying comprises immersing the substrate in a solution of the coating.

106. 104. The method of claim 103, wherein said applying comprises placing said substrate over a solution of said coating.

107. 104. The method of claim 103, wherein the applying comprises spraying, dripping, or depositing the coating onto the substrate.

108. 108. The method of claim 107, wherein the applying is carried out for 1 to 24 hours, 5 to 24 hours, 5 to 20 hours, 8 to 20 hours, 8 to 15 hours, or 9 to 11 hours.

109. 104. The method of claim 103, wherein the one or more cross-linking agents are selected from the group consisting of 1,4-butanediol diglycidyl ether (BDDE), hexamethylene diisocyanate (HDMI), glutaraldehyde (GA), genipin, and combinations thereof.

110. 104. The method of claim 103, wherein (c) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.

111. 104. The method of claim 103, wherein the washing is performed with water.

112. 104. The method of claim 103, wherein (d) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.

113. 104. The method of claim 103, wherein (e) is carried out for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.

114. 104. The method of claim 103, wherein following (e), the produced scaffold is subjected to drying.

115. 104. The method of claim 103, further comprising applying one or more therapeutic agents to the scaffold.

116. 116. The method of claim 115, wherein the one or more therapeutic agents are present in the polymer, the coating, both the polymer and the coating, and / or are applied to at least a portion of the exterior of the scaffold.

117. 104. The method of claim 103, wherein the degradation of the patterned polymeric substrate is tunable based on the concentration of the cross-linking agent.

118. 104. The method of claim 103, comprising washing the substrate after subjecting the substrate to one or more cross-linking agents.

119. 104. The method of claim 103, wherein the scaffold is generated in a defined shape.

120. 120. The method of claim 119, wherein the defined shape is a pre-programmed macrostructure that is constructed based on forming with a mandrel or that is 3D printed.

121. 10. A method of reinforcing soft tissue in an individual in need thereof, comprising applying an effective amount of the scaffold of claim 1 to one or more soft tissue sites of said individual.

122. 122. The method of claim 121, wherein the soft tissue comprises muscle, tendon, ligament, fascia, fat, skin, nerve, blood vessel, or a combination thereof.

123. 123. The method of claim 121 or 122, wherein the soft tissue comprises an injury, a surgical site, a congenital deformity, diseased tissue, or a combination thereof.

124. 122. The method of claim 121, wherein the soft tissue is soft tissue of the breast, stomach, abdomen, groin, leg, arm, hand, face, pelvis, uterus, vagina, penis, cervix, brain, nose, ear, eyelid, heart, kidney, liver, bladder, prostate, larynx, trachea, or combinations thereof.

125. 122. The method of claim 121, wherein the soft tissue comprises breast tissue for breast reconstruction, breast reduction, or breast augmentation.

126. 122. The method of claim 121, wherein the soft tissue comprises a hernia.

127. 122. The method of claim 121, wherein said applying comprises attaching said scaffold to said soft tissue of said individual and / or tissue adjacent to said soft tissue of said individual.

128. 128. The method of claim 127, wherein said attaching is further defined as the use of suturing, stapling, or surgical adhesive to attach said scaffold to said soft tissue of said individual and / or tissue adjacent to said soft tissue of said individual.

129. 129. The method of claim 128, wherein the suture is a purse string suture, a running suture, an interrupted suture, a buried suture, a deep suture, or a subcutaneous suture.

130. 130. The method of claim 128 or 129, wherein the suture of the suturing is absorbable.

131. 130. The method of claim 129, wherein the suture of the suture is non-absorbable.

132. 1. A flexible sheet comprising one or more biodegradable polymers and one or more ECM materials, the sheet comprising a plurality of patterned unit cell structures aligned in adjacent rows of a series of vertically alternating unit cell structures, each of the series of vertically alternating unit cell structures generally comprising a shaped pore having a centerline, the centerline being longer than two substantially equal length lines each perpendicular to opposite ends of the centerline, the alternating pattern configured such that each of the ends of the centerline of a pore is approximately perpendicular to the centerline of a pore of an adjacent unit cell structure.

133. 133. The flexible sheet of claim 132, wherein the unit cell structure is composed of one or more biodegradable polymers.

134. 134. The flexible sheet of claim 132 or 133, wherein the sheet comprises a coating of one or more ECM materials.

135. 135. The flexible sheet of claim 134, further defined as said unit cell structure comprising one or more coatings of ECM material.

136. 133. The flexible sheet of claim 132, wherein the pores are filled with the coating.

137. 133. The flexible sheet of claim 132, wherein the one or more ECM materials comprises type I collagen.

138. 133. The flexible sheet of claim 132, wherein the sheet is contained within a suitable package.

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