Bio-printed soft tissue enhancing stent

Abstract

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

Description

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

[0002] The present disclosure relates at least to the fields of chemistry, biology, biocompatible structures, wound care and medicine, including compositions and materials for forming biological scaffold structures that can be used in individuals, such as for soft tissue enhancement and / or regeneration. There are a variety of materials that can be used to provide tissue enhancement and / or fill excised tissue to reconstruct the natural shape of soft tissue. Summary of the invention

[0003] Embodiments of the present disclosure include systems, methods and compositions related to soft tissue regeneration, enhancement and / or repair. In various embodiments, the present disclosure relates to a specific structure for soft tissue regeneration, enhancement and / or repair, wherein the structure provides structural elements and therapeutic elements to promote such activities. In specific embodiments, the present disclosure relates to a scaffold, which is configured to mechanically support soft tissue while also delivering at least the biomolecules that strengthen the regeneration and repair of soft tissue, and in specific cases, the scaffold causes minimal immunogenic response or does not cause an immunogenic response in a recipient individual. In specific embodiments, the present disclosure provides a scaffold composition, which is manufactured by the following materials, which minimizes immunogenic response in a host while providing a structural framework for tissue regeneration. In embodiments, the scaffold brings dual benefits to the recipient individual by providing: (1) a physical structure consisting of a defined unit cell structure to provide support and a suitable polymer to impart appropriate strength and flexibility for in vivo use; and (2) a therapeutic component as a coating (and / or within the physical structure) to enable the proliferation and / or infiltration of cells and / or tissues to be enhanced at a soft tissue site in need. In some embodiments, the scaffold serves as a delivery component to deliver the therapeutic component. In specific embodiments, the scaffold utilizes a specific pattern to reproduce natural mechanical tissue properties that other synthetic scaffolds cannot. In embodiments, three-dimensional (3D) printing produces the scaffold.

[0004] Specific embodiments provide a scaffold consisting of one or more biodegradable polymers and one or more extracellular matrix materials, wherein the scaffold consists of a row of unit cell structures or unit patterns of a specific design that are repeated. In embodiments, the design of the unit cell structure or unit pattern comprises a specific shape, including the shape of a structure that is generally a capital letter "I". In a specific embodiment, the scaffold comprises a row of unit cell structures or unit patterns of capital letters "I" in a vertically alternating configuration.

[0005] Embodiments of the present disclosure provide artificial support structures, which include one or more biodegradable polymers and one or more extracellular matrix materials, and the support structure also includes a plurality of unit patterns, each unit pattern includes a plurality of filaments arranged continuously, symmetrically and regularly thereon, each unit pattern is composed of the edge of a closed shape so as to form a hole therein, wherein a plurality of unit patterns are connected so as to have intersections each other, and the number of intersections is the same as the number of the edges passing through the intersections. In a specific embodiment, one or more extracellular matrix materials include collagen I. In certain embodiments, at least one unit pattern has a diameter between about 200 microns to about 3.5 mm. In some aspects, at least one unit pattern has a diameter between about 1.5 mm to about 3 mm or about 1.782 mm to about 2.97 mm. The biodegradable polymer material may also include one or more extracellular matrix materials, in a specific embodiment, such as collagen I.

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

[0007] In some embodiments, four unit patterns are connected to have four intersections with each other and have four sides passing through or crossing the four intersections, and the space surrounded 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 "I" of the English alphabet, and the short sides of the sides of the closed shape of each unit pattern have the same length as each other, and the long sides have the same length as each other, so that in some embodiments, the space surrounded by the four unit patterns has the same shape as each unit pattern. In the closed shape, in a specific case, the length ratio of the short side to the long side is 1:3.

[0008] In various embodiments, the artificial support structure has an ultimate tensile strength between about 4MPa to about 5MPa, about 4.05MPa to about 4.7MPa, or about 4.12MPa to about 4.50MPa. In some embodiments, the artificial support structure has an elastic modulus of about 2.8MPa to about 4.2MPa, about 3.00MPa to about 4.10MPa, or about 3.06MPa to about 4.00MPa. In certain embodiments, the artificial support structure has a suture holding strength of about 20N to about 26N, about 21N to about 25N, or about 22.03N to about 24.27N. In a specific embodiment, the artificial support structure has a burst strength of about 140N to about 170N, about 145N to about 163N, or about 147.14N to about 161.26N. 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 encompass artificial support structures, which include one or more biodegradable polymers and one or more extracellular matrix materials (such as collagen I), and the support structure also includes a plurality of unit patterns, each unit pattern including multiple filaments repeatedly arranged to form columns or rows symmetrical to each other, each unit pattern consisting of the edges of a closed shape so as to form a hole inside it, wherein the columns or rows along which the plurality of unit patterns are repeatedly arranged have an Eulerian trajectory. In a specific embodiment, at least one unit pattern has a diameter between 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 also includes one or more extracellular matrix materials, such as collagen I.

[0010] In certain embodiments, a plurality of connected unit patterns form substantially planar sheets, such as a plurality of connected unit patterns form three-dimensional macro structures. In particular, and in various embodiments, the artificial support structure has a thickness between about 0.5mm to about 1.5mm, about 0.7mm to about 1.3mm or about 0.9mm to about 1.1mm. In some cases, the artificial support structure contains 1 to 5 layers, and these layers can have a thickness between about 0.10mm to about 0.3mm, about 0.15mm to about 0.25mm or about 0.18mm to about 0.22mm. In some embodiments, one or more long filaments in multiple long filaments have a diameter less than about 550 microns, 500 microns or 400 microns.

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

[0012] In various embodiments, the artificial support structure has an ultimate tensile strength between about 4MPa to about 5MPa, about 4.05MPa to about 4.7MPa, or about 4.12MPa to about 4.50MPa. In some embodiments, the artificial support structure has an elastic modulus of about 2.8MPa to about 4.2MPa, about 3.00MPa to about 4.10MPa, or about 3.06MPa to about 4.00MPa. In certain embodiments, the artificial support structure has a suture holding strength of about 20N to about 26N, about 21N to about 25N, or about 22.03N to about 24.27N. In a specific embodiment, the artificial support structure has a burst strength of about 140N to about 170N, about 145N to about 163N, or about 147.14N to about 161.26N. 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 invention include a support, the support includes a patterned polymer substrate, the patterned polymer substrate has one or more extracellular matrix (ECM) material coating thereon, wherein the pattern of the polymer substrate includes a series of adjacent rows of unit cell structures, each unit cell structure is generally in the shape of the letter "I", and the unit cell structure is arranged in a row of the patterned polymer substrate in a vertical alternating pattern of the unit cell structure. In certain embodiments, the unit cell structure in the series is further defined as a hole formed as a center line, the length of the center line is greater than the length of two substantially equal length lines of the opposite ends of each perpendicular to the center line, and wherein the alternating pattern is configured so that each end of the center line of the hole is generally perpendicular to the center line of the hole of the adjacent unit cell structure. In some embodiments, the support is configured as one or more sheets, each sheet including a first planar side and a second planar side, and in particular aspects, the support includes 1, 2, 3, 4 or 5 sheets, or includes at least or no more than 1, 2, 3, 4 or 5 sheets. In some embodiments, the plurality of sheets are arranged such that a planar side of one sheet is adjacent to a planar side of another sheet.

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

[0015] In various embodiments, the polymer matrix comprises polycaprolactone, polydioxanone, or a combination thereof. In certain cases, one or more ECM materials 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, cattle, pig, or is recombinant. In specific 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 is recombinant.

[0016] In a specific embodiment, the support includes a coating that 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. In a specific embodiment, the coating fills the holes of a plurality of unit cell structures of the support, fills the holes of most of the unit cell structures of the support, or fills the holes of substantially all of the unit cell structures of the support. In at least some cases, the coating does not fill the holes of most of the unit cell structures of the support or does not fill the holes of substantially all of the unit cell structures of the support. In a specific embodiment, the thickness of the support is no greater than 1 mm.

[0017] In various embodiments, the scaffold comprises one or more therapeutic agents, and in some embodiments, 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.

[0018] Embodiments of the present disclosure include methods of producing any scaffold 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 crosslinking agents; (d) optionally washing the substrate; and (e) subjecting the substrate to conditions at a temperature below 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. In some cases, the polymer substrate is composed of polycaprolactone, polydioxanone, or a combination thereof. In specific embodiments, applying comprises: immersing the substrate in a coating solution, placing the substrate on top of the coating solution, and / or spraying, dripping, and / or placing the coating on the substrate. As an example, the application may be performed for 1 hour to 24 hours, 5 hours to 24 hours, 5 hours to 20 hours, 8 hours to 20 hours, 8 hours to 15 hours, or 9 hours to 11 hours. In a specific embodiment, 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 some cases, (c) is performed for about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours. In some embodiments, washing is carried out with water, and in some aspects, (d) is carried out for about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours or 24 hours. In some embodiments, (e) is carried out for about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours or 24 hours. In at least some cases, after (e), the bracket produced is subjected to drying. The method may also include applying one or more therapeutic agents to the stent, in some cases, the one or more therapeutic agents are such as present in a polymer, a coating, both a polymer and a coating, and / or applied to at least a portion of the outside of the stent in a particular aspect. In certain embodiments, the degradation of the patterned polymer substrate can be regulated based on the concentration of the cross-linking agent. In a specific embodiment, the method may include washing the substrate after subjecting the substrate to one or more cross-linking agents.In certain embodiments, the scaffold is produced as a defined shape, such as configured based on forming over a mandrel, or as a 3D printed pre-programmed macrostructure.

[0019] Embodiments of the present disclosure include methods for enhancing soft tissue in individuals in need, the method including applying any support covered herein by an effective amount to one or more soft tissue sites of an individual. In specific embodiments, soft tissue may include muscle, tendon, ligament, fascia, fat, skin, nerve, blood vessel or a combination thereof, and in specific aspects, soft tissue includes injury, surgical site, birth malformation, pathological tissue or a combination thereof. In specific embodiments, soft tissue belongs to 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 specific cases, soft tissue includes mammary tissue for breast reconstruction, breast reduction or breast augmentation, or soft tissue includes hernia. In specific embodiments, applying includes fixing support to individual soft tissue and / or tissue adjacent to the soft tissue of an individual. In some cases, fixation is further defined as suturing, stapling or using surgical glue to fix the stent to the individual's soft tissue and / or the individual's tissue adjacent to the soft tissue, and in certain embodiments, the suturing is a purse string suture, a continuous suture, an interrupted suture, a buried suture, a deep suture or a subcutaneous suture. The suture of the suturing is absorbable or non-absorbable.

[0020] Embodiments of the present disclosure encompass flexible sheets comprising one or more biodegradable polymers and one or more ECM materials, the sheet comprising a plurality of patterned unit cell structures arranged in adjacent rows of a series of vertically alternating unit cell structures, each unit cell structure generally comprising a hole shaped to have a center line, the length of the center line being greater than the length of two substantially equal length lines of opposite ends each perpendicular to the center line, wherein the alternating pattern is configured such that each of the ends of the center line of the hole is generally perpendicular to the center line of the hole of the adjacent unit cell structure. In certain embodiments, the unit cell structure is composed of one or more biodegradable polymers, and the sheet comprises a coating of one or more ECM materials. In a specific embodiment, the flexible sheet is further defined as a unit cell structure comprising a coating of one or more ECM materials. In some cases, the hole is filled with a coating, and the one or more ECM materials include type I collagen. In some cases, the sheet is contained in a suitable package and is sterile in a specific embodiment.

[0021] It is contemplated that any embodiment discussed in this specification may be implemented with respect to any method or composition of the present disclosure, and vice versa, and that different embodiments may be combined. In addition, the compositions of the present disclosure may be used to implement the methods of the present disclosure. It is contemplated that the initially filed claims cover claims that are subordinate in many respects to any filed claim or combination of filed claims. The present disclosure is not limited to these exemplary embodiments and applications, nor to the manner in which the exemplary embodiments and applications are operated or described herein. In addition, the drawings may show simplified views or partial views, and the sizes of the elements in the drawings may be exaggerated or otherwise not to scale.

[0022] According to the detailed description below, other objects, features and advantages of the present invention will become apparent. However, it should be understood that the detailed description and specific examples, although indicating specific embodiments of the present disclosure, are given by way of illustration only, because various changes and modifications within the spirit and scope of the present invention will become apparent to those skilled in the art based on the detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The following drawings constitute part of this specification and are included to further illustrate certain aspects of the present invention. The present disclosure may be better understood by referring to one or more of these drawings in conjunction with the detailed description given herein.

[0024] Figure 1A . Illustration of an implementation scheme of multiple unit patterns.

[0025] Figure 1B .A close-up view of an example of multiple unit patterns configured in a 3D printed scaffold.

[0026] Figure 1C .Top view of an example of a scaffold prior to deposition of an extracellular matrix coating.

[0027] Figure 1D . A view of an example of a scaffold prior to deposition of an extracellular matrix coating.

[0028] Figure 1E . Side view of an example of a scaffold prior to deposition of an extracellular matrix coating.

[0029] Figure 1F .Side view of an example of a bracket showing scale.

[0030] Figure 2 .Microscopic images of polyglactin 910 mesh* and PCL soft tissue reinforcement scaffold (STRS)** at 0 and 6 weeks (*: longitudinal direction, **: pattern P).

[0031] Figure 3A.Ultimate tensile strength (UTS) of polyglactin 910 webs over time (longitudinal direction).

[0032] Figure 3B .Young's modulus (YM) of polyglactin 910 mesh over time (longitudinal direction).

[0033] Figure 4A .UTS (Ultimate Tensile Strength) of PCL STRS over time.

[0034] Figure 4B .YM (Young's modulus) of PCL STRS over time.

[0035] Figure 5 Results of the enzymatic degradation test (BDDE x %: collagen matrix with x % BDDE).

[0036] Figure 6 . UTS diagram comparing the STRS of the present disclosure to the TnR network and ADM control (MegaDerm).

[0037] Figure 7 .Comparison of cell infiltration between ADM and STRS.

[0038] Figure 8 . Graph showing degradation control after adjusting the cross-linker concentration.

[0039] Fig. 9 An example of the manufacturing process of .STRS.

[0040] Fig.10 An example of freeze drying conditions for one or more actions in the STRS manufacturing process. The term "9999" in SVP refers to maintaining a constant temperature (different from room temperature) until the sample is recovered.

[0041] Fig.11 .Comparison of UTS plots of different STRS made with PCL or PDO and MegaDerm at a specific line width.

[0042] Fig.12 Bubble charts of STRS and MegaDerm. DETAILED DESCRIPTION

[0043] Unless otherwise defined, scientific and technical terms used in conjunction with the present teachings described herein shall have the meanings commonly understood by those of ordinary skill in the art. In addition, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0044] This specification describes exemplary embodiments and applications of the present disclosure. However, the present disclosure is not limited to these exemplary embodiments and applications, nor to the modes of operation or application of the exemplary embodiments and applications described herein. Other embodiments, features, objects and advantages of the present teachings will be apparent from the specification and drawings and claims. In addition, the drawings may show simplified views or partial views, and the sizes of the elements in the drawings may be enlarged or otherwise not proportional. The division of chapters in this specification is only for ease of viewing and does not limit any combination of the elements discussed.

[0045] I. Examples of definitions

[0046] The use of the word "a" when used in conjunction with the term "comprising" may mean "one", but it is also consistent with the meaning of "one or more", "at least one", and "one or more than one".

[0047] Throughout this application, the term "about" is used to indicate that a value includes the inherent variation of error for the measurement or quantitative method.

[0048] It is contemplated that any method or composition described herein can be implemented with respect to any other method or composition described herein, and that the different embodiments can be combined.

[0049] 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 can be used to mimic an extracellular matrix environment to support the adhesion, proliferation, and differentiation of living cells. In certain cases, bioinks can provide materials that promote soft tissue augmentation.

[0050] As used herein, "extracellular" when used to refer to, for example, "extracellular material," "extracellular structure," "extracellular matrix," "extracellular construct," and "extracellular component" may indicate a property that exists outside of a cell, and may refer to synthetic or natural materials. Examples of extracellular materials include synthetic polymers and natural polymers; metabolites; ions; various protein and non-protein substances (e.g., DNA, RNA, lipids, microbial products, etc.), such as collagen, proteoglycans, hormones, growth factors, cytokines, chemokines; various enzymes, including, for example, digestive enzymes (e.g., trypsin and pepsin), extracellular proteases (e.g., matrix metalloproteinases, disintegrin and metalloproteinases with thrombospondin motifs (ADAMTS), cathepsins) and antioxidant enzymes (e.g., extracellular superoxide dismutase); protein hydrolysis products; extracellular Matrix proteins (such as elastin, glycosaminoglycans (GAGs), laminin, fibronectin, etc.), selected cell populations, small molecules and small molecule inhibitors, antibiotics, antimicrobial agents, nanoparticles, mesoporous silica, silk fibroin, enzymatic degradation sites; anti-fibrotic agents, such as anti-transforming growth factor β (anti-TGF-β) and anti-tumor necrosis factor α (anti-TNF-α); pro-angiogenic 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.

[0051] As used herein, the term "hole" may refer to an opening in a stent. A hole may or may not have a specific shape. The shape of the hole may not be circular or square, but may generally be the shape of the letter "I". The hole may include the shape of a center line with two shorter vertical lines at opposite ends of the center line.

[0052] As used herein, the term "resorbable" may refer to the ability of a device to undergo biodegradation (chemical breakdown by biological agents) in a biological environment and to have the degradation products removed by cellular activity.

[0053] As used herein, "scaffold" can refer to a biocompatible and bioabsorbable structure that can be implanted in the body to provide support and / or promote cell adhesion and tissue regeneration (such as for diseased tissue or wound repair) used in tissue engineering. The scaffold can include a repetition that limits a unit pattern in adjacent rows. The scaffold can be used in, for example, soft tissue areas, including regeneration and / or enhancement for cartilage, skin, organs, muscles, tendons, ligaments, fascia, fat, skin, nerves, blood vessels, or a combination thereof. The scaffold can be used in the 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 term "artificial support structure" can be used interchangeably with the term "scaffold" herein.

[0054] 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 that defines a defined hole. The outline and the hole may generally have the same shape. The unit cell structure may be a structure having the general shape of the letter "I".

[0055] II. Brackets and their uses

[0056] There are a variety of material options to provide tissue augmentation or fill in resected tissue to reconstruct the natural shape of soft tissue, including in areas where resected tissue was taken. Examples of materials include acellular dermal matrix (ADM) bioscaffolds, obtained from decellularized human, bovine or porcine dermis; fat or other transplanted tissue fillers; synthetic polymer-based scaffolds; or combinations thereof. However, certain materials have a number of disadvantages, including, for example, causing a deleterious immunogenic response in the recipient (such as with ADM); lack of support, protection and reinforcement of the dermis to enable shape maintenance or support; and lack of the ability to provide a robust cellular infiltration / remodeling response after implantation, as examples.

[0057] Certain bioscaffolds may not provide a composition of extracellular matrix proteins that promotes cellular ingrowth into the bioscaffold, and such scaffolds may therefore not enhance tissue regeneration, which can aid in patient recovery. In certain embodiments, the disclosed compositions utilize a combination of 3D printed polymer scaffolds and animal-derived collagen in a specific manner as an improvement over other synthetic scaffolds by providing natural mechanical tissue properties that are lacking in other synthetic scaffolds.

[0058] Disclosed herein are compositions, methods and materials relating to implantable acellular scaffolds containing native extracellular matrix (ECM) proteins that can elicit a robust regenerative response while minimizing undesirable immunogenic responses from the host. In addition to enhancing host cell ingrowth, regeneration and repair, such scaffolds can also provide support to wounds or fill postoperative voids.

[0059] The present disclosure relates to three-dimensional printing of scaffolds of different macroscopic shapes based on bioprinting configurations, including at least flat sheets and / or 3D scaffold structures. The scaffold compositions can provide cushioning and structural support for other tissues, providing supplementary support, protection, enhancement, and coverage within any soft tissue (including muscle, tendon, ligament, fascia, fat, skin, nerve, blood vessel, or a combination thereof). The soft tissue can be located anywhere in the body, and the scaffold can be configured to stimulate host cell remodeling.

[0060] Scaffolds can be biodegradable or resorbable. They can be used to support, repair, enhance and strengthen defects in soft tissues that require the addition of material where there is weakness or void (or both). Scaffolds can facilitate the repair of defects that require the addition of reinforcement, regeneration and / or bridging material, for example, to achieve a desired surgical outcome.

[0061] In various embodiments, the scaffold composition can minimize the host immunogenic response, provided that the scaffold can include user-selected or desired components. Unlike the current acellular dermal matrix (ADM) products that can trigger "transplantation and host response", the various scaffold compositions covered herein allow control of components and allow standardization of clinical results in patients and between patients. Compared with other available products, the scaffold provides increased support and enhancement, and relative to currently available products in the art, the scaffold can provide controlled, enhanced elasticity and tension. Utilizing 3D printing and this specific pattern / material combination has the ability to reproduce the natural mechanical tissue properties that other synthetic scaffolds cannot.

[0062] The present disclosure relates to printable scaffold compositions that simulate acellular matrix products, but have unique printability and the ability to support tissue and / or organ growth that can be printed into 2D and 3D shapes. The scaffold compositions described herein are improved, at least because they minimize concerns about donor availability, provide reproducibility, alleviate increasing costs, eliminate concerns about tissue quality, variability, and the possibility of contamination, and provide minimal immunogenic products. Scaffolds (including unit cell patterns and materials) can also be customized according to clinical needs to give end-users different mechanical properties required, which cannot be accomplished with other synthetic scaffolds or allografts / xenograft tissues. The scaffold can be configured to be used permanently in vivo.

[0063] The scaffolds covered herein can provide the necessary porosity to allow cell infiltration and provide a sufficiently large niche for cell attachment, ultimately directing cell fate to a remodeling / regeneration phenotype. In addition, from a mechanical / structural perspective, the scaffold includes a plurality of specific unit cell structures, and the arrangement of the unit cell structures within the scaffold structure provides the scaffold with appropriate mechanical strength and elasticity to make it physiologically relevant and useful as a supporting matrix. These features can be provided by a scaffold structure using, for example, an extracellular material composition as disclosed herein (such as a composition comprising collagen I), thereby providing the necessary structural integrity and heating properties.

[0064] The unit cell structural configuration of the scaffold imparts specific physical properties to the scaffold, and the construct can always have a consistent surface morphology as well as an engineered microarchitecture (controlling properties such as, for example, porosity, fiber diameter, spacing, matrix height, fiber orientation, etc.) that provides an appropriate scaffold for robust wound healing, regeneration, infiltration and / or remodeling responses.

[0065] Furthermore, the constructs can, for example, provide cushioning as well as structural and mechanical support to other tissues, provide supplemental support, protection, reinforcement, and coverage within soft tissues, while stimulating host cell remodeling.

[0066] A. Bracket material

[0067] Provide a scaffold composition, the scaffold composition can include one or more biodegradable polymers, one or more extracellular matrix materials and optional other components, such as one or more therapeutic agents. The unique combination of biodegradable polymers and extracellular matrix materials provides a suitable support matrix for remodeling together, and provides a fertile environment for cell infiltration. In various embodiments, the combination of polymer construct material and bioconstruct material also provides a solid support for adding other molecular parts.

[0068] The stent may include natural and / or synthetic polymers, including any polymer that provides mechanical stability, and it may have a consistent degradation profile, which allows for greater predictability for individuals receiving the stent. The stent composition may include any suitable natural or synthetic polymer or a combination or blend thereof. The synthetic polymer may be biodegradable and may include, for example, polycaprolactone (PCL), poly(p-dioxanone) (PDO), a combination thereof, or any other type of polymer.

[0069] The 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 a syringe. These components can be, for example, pneumatic, piston or screw driven. A pneumatically driven syringe can, for example, deposit the liquefied polymer in sequential layers to generate a construct that will eventually be cross-linked.

[0070] Synthetic polymers can be deposited as bio-inks by 3D printers. Bio-inks may or may not contain bioactive molecules. Compared with traditional polymer-based compositions, some bio-inks that contain bioactive molecules in addition to polymers may have to be deposited under milder conditions relative to polymer-based compositions. This may be due to the relatively finer properties of the bio-ink structure (e.g., higher water content, non-crystalline structure, etc.). Therefore, bio-printing process parameters such as printing pressure or nozzle / syringe diameter can be considered when reducing the shear stress on some bio-inks to prevent the generation of damaged or lysed cells that may affect the cell viability in the bio-ink. Other parameters that can be considered and controlled accordingly include, for example, printing temperature (e.g., a lower temperature than polymer-based compositions), uniformity of diameters of filaments constituting unit cells, angles when filaments interact, color bleeding when filaments intersect together, and maintenance of shape fidelity after printing but before cross-linking with polymer-based compositions. In any case, the polymer can be deposited as, for example, droplets or streams using defined process parameters to ensure scaffold manufacturing while maintaining the structural integrity of the deposited composition.

[0071] Each unit cell of the scaffold structure may comprise a polymer or a blend of polymers and may comprise a coating of an ECM material, which may or may not comprise collagen. It should be understood that the extracellular material of the scaffold structure (which may comprise PCL and / or PDO and / or another soluble or liquefiable polymer) may help provide structural integrity and functionality to the scaffold structure and the unit cells that comprise the structure.

[0072] The extracellular matrix component of the scaffold may include one or more of the following: 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, antimicrobials, nanoparticles, mesoporous silica, silk fibroin, and enzymatic degradation sites.

[0073] In certain embodiments, a scaffold may include a coating of an ECM material (but not a collagen coating), a collagen coating, or a combined collagen / ECM material coating.

[0074] B. Bracket shape and structure

[0075] The present disclosure generally relates 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 that are suitable for promoting cell infiltration, tissue regeneration and minimizing the risk of adverse immune response and / or pathogen contamination in patients.

[0076] The stent of the present disclosure includes a plurality of unit parts having a defined shape and structure. The stent may be composed of a plurality of unit cell structures arranged in a constant or clear pattern or forming a constant or clear pattern. The stent may be composed of a plurality of unit patterns, which may also be referred to as unit cell structures, each of which includes a plurality of filaments arranged continuously, symmetrically and regularly thereon. Each unit pattern may be composed of the edges or contours of a closed shape, which then forms a hole inside. The plurality of unit patterns in the stent may be connected to have intersections with each other, and the number of intersections may be the same as the number of edges passing through the intersections ( Figure 1A ).like Figure 1A As shown, for the unit pattern 100 , the number of intersections 101 is the same as the number of edges / lines 102 at the specific intersections 101 .

[0077] The stent may be considered as an artificial support structure comprising a plurality of unit patterns, each unit pattern comprising a plurality of filaments that are repeatedly arranged to establish columns or rows that are symmetrical to each other. In this case, each unit pattern may be composed of edges of a closed shape that creates a hole inside, and the columns or rows along which the plurality of unit patterns are repeatedly arranged may have an Euler trajectory.

[0078] The scaffold may include a patterned polymer substrate having a coating of one or more ECM materials, and the pattern of the polymer substrate may include a series of adjacent rows of unit cell structures, each unit cell structure generally being in the shape of the letter "I". In this case, the unit cell structures can be arranged in the rows of the patterned polymer substrate in a vertical alternating pattern of unit cell structures. The unit cell structures in the series may be further defined as including holes shaped as centerlines having a length greater than the length of 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 of the ends of the centerline of the hole is generally perpendicular to the centerline of the hole of the adjacent unit cell structure.

[0079] Figure 1B A close-up image of an example of a bioprinted scaffold prior to deposition of one or more ECM materials thereon is shown. The filaments that make up the outline of an I-shaped unit cell structure can be deposited by a 3D printer using a specific line width. Figure 1C and Figure 1D Provides Figure 1B Images at different angles of the entirety of one sheet of a scaffold of the same unit cell structure configuration. A given row or column in the scaffold may or may not be approximately diagonal relative to an edge of the scaffold structure. Figure 1E and Figure 1F Images of different angles of the side of one sheet of a scaffold are provided. The thickness of the scaffold can be predetermined by depositing the 3D printed polymer.

[0080] The degradation of the scaffold composition can occur over time after surgical implantation. The degradation of the scaffold composition can occur partially or completely in 6,7,8,9,10,11 or 12 months or approximately in these times. The degradation of the scaffold composition can occur partially or completely in 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 or approximately in these times. The degradation of the scaffold composition can occur partially or completely in 1,2,3,4,5,6,7,8,9,10 or more years or approximately in these times. The degradation of the scaffold composition can occur within 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, 8-9 or 9-10 years or approximately within these times. The integration of host cells into the porous scaffold can be carried out throughout the degradation process so that the infiltrating cells will degrade the polymer and secrete their own extracellular matrix in an attempt to regenerate the tissue. The degradation profile of the scaffold composition is definable and predictable throughout the manufacturing batch, which is an improvement over acellular dermal matrix constructs currently available in the art.

[0081] A plurality of connected unit cells in the scaffold structure may form a substantially planar sheet.

[0082] Artificial support structure or support can comprise specific size and / or mechanical characteristic that can give natural mechanical tissue characteristic.Composition can have specific thickness, such as between about 0.5mm to about 1.5mm, about 0.7mm to about 1.3mm or about 0.9mm to about 1.1mm.In some cases, the layer for composition can have the thickness between about 0.10mm to about 0.3mm, about 0.15mm to about 0.25mm or about 0.18mm to about 0.22mm.When utilizing multiple layers, independent layer can have or can not have the same thickness.For the long filament of composition, they can have the diameter less than about 550 microns, about 500 microns or about 400 microns.

[0083] The artificial support structure or scaffold may have an ultimate tensile strength between 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 the elastic modulus, any composition may have a modulus 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 scaffold may be fixed to the soft tissue by any means (including with sutures), 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. For additional mechanical properties, the artificial support structure may have a burst strength of about 140N to about 170N, about 145N to about 163N, or about 147.14N to about 161.26N, and / or may have a tear resistance of about 18N to about 26N, about 19N to about 25N, or about 19.87N to about 24.92N.

[0084] The support can be printed into a desired shape before it is needed (such as put into a warehouse or sold commercially). In this case, the surface of the support can be 2D, and the printed support can be 3D and can be a prefabricated shape, or it can be customized according to the needs of a specific patient, such as a specific wound or space that the patient needs to adapt personally. The shape of the support can be based on the mandrel or preprogrammed macrostructure that will be printed by 3D. The design of the support shape can be produced using computer-aided manufacturing (CAM) software before manufacturing. For example, the support can be a sheet shape, such as a square or rectangle, or it can be a bowl shape or other 3D ultrastructures that match the patient's anatomical structure. The sheet can be cut into a specific size and / or shape based on the needs of the patient. The support can be stored or sold commercially in any form, including sheet form or as a printed 3D structure.

[0085] C. Additional Scaffold Components

[0086] The stent of the present disclosure can be manufactured so that the structure contains one or more therapeutic agents or other reagents. These reagents can be eluted from the stent, as part of the coating on the stent, their combination, etc. The reagent can be used as a therapeutic agent for tissues (such as wound healing, diseased tissue healing, etc.) adjacent to the stent, near the stent, etc. The stent can be configured so that it can be resorbed within a period of time (such as described above) to allow one or more reagents to be delivered within this period of time. These reagents can be used for wound healing, scar prevention, fibrosis prevention and / or long-term treatment of chronic or recurrent medical conditions. The release of the reagent from the stent can be a modified release, such as immediate release, sustained release, delayed release or controlled release, thereby controlling the rate of release of the reagent.

[0087] The reagent can be provided on one or more outer surfaces of the support and / or incorporated into the support. The reagent can be mixed with a precursor polymer solution and incorporated into a polymer matrix during manufacture, where release occurs when the polymer degrades. The reagent can be incorporated into the device by placing the device in a reagent solution and allowing the reagent to be adsorbed to the device surface and released by controlling the desorption rate. The reagent can be covalently grafted to a functional group on the device polymer chain. The covalently bound group can be selected as an unstable group, for example, an ester or thio-β ester group, which will cleave and release the reagent in a physiological environment. The reagent can be incorporated into an ECM coating.

[0088] The time period for the agent to elute from the stent is substantially the same as the time period for the stent to be used (including at least a portion of the stent being resorbed by the body). Substantially all of the agent may elute from the stent prior to partial or complete absorption by the body; in this case, a sufficient amount of the agent is used to provide adequate healing at the site of use.

[0089] The one or more therapeutic agents can be any kind of individual suitable for receiving the composition for any purpose. The reagents associated with the composition can be customized according to the treatment needs of the individual. For example, based on the individual's medical condition, the individual may need one or more specific reagents as part of the composition, and thus manufacture a composition comprising the reagent. Based on the individual's medical condition, the individual may need one or more specific reagents as part of the composition, and the composition comprising the required reagents is obtained after manufacture, such as after storage, commercially, etc.

[0090] The therapeutic agent can be a bioactive molecule, a growth factor, a cytokine, a chemokine, a drug, a hormone, an antibiotic, an analgesic, a hemorheological agent, a vasoconstrictor, an anti-inflammatory, an anti-fibrotic agent, a wound healing agent, a radiation protection material, an antifungal agent, a contraceptive, or any combination thereof. In the case where the therapeutic agent is a growth factor, the growth factor can be epidermal growth factor, keratinocyte growth factor,

[0091] Growth factor, transforming growth factor (including TGF-α, TGF-β1, TGF-β2), vascular endothelial growth factor, platelet-derived growth factor, blocking factor, scavenger, antagonist, differentiation factor or reagent that binds to a specific promoter. In the case where the therapeutic agent is a cytokine, the cytokine can be interleukin-2 (IL-2), IL-7, IL-15 or a combination thereof. In the case where the therapeutic agent is a chemokine, the chemokine can be any one or more chemokines in the following subclasses: CXCL-, CCL-, CX3-, 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 a combination thereof. In the case where the therapeutic agent is a drug, the drug can be a small molecule, an antibody, a nucleic acid, a polypeptide, a carbohydrate, or a combination thereof. In the specific case where the therapeutic agent is a drug, the drug can be an analgesic, an anesthetic, an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, a hormone, a vitamin, a mineral, an immune agent, or a mixture thereof.

[0092] The agent can be a hormone, an antibiotic, an analgesic, a hemorheological preparation, a vasoconstrictor, an anti-inflammatory, an antifibrotic agent, a wound healing agent, a radiation protection material, an antifungal agent, a contraceptive or any combination thereof. In particular cases, the agent is a drug such as AMD3100, tacrolimus, 2-octyl cyanoacrylate, Alevicyn, Artiss, becaplermin, betaine / polyhexanide, cadexomer iodine. Collagenase, Dermabond, Eletone cream, Episalvan, Evicel, fibrin sealant, Filsuvez, topical hypochlorous acid, Lodosorb, NexoBrid, oil gel-S10, topical petrolatum and mineral oil, Prontosan, proteolytic enzymes, Regranex gel, Santyl (sandalyl salicylate), TachoSil, Tisseel VH, Tropazone or a combination thereof. When the agent is a hormone, the hormone can be an estrogen.

[0093] If necessary, the scaffold composition may include one or more growth factors. The growth factor may be, for example, any one of the following or a combination thereof: GM-CSF, NGF, SCF, TGF-β, EGF, VEGF, etc.

[0094] The scaffold composition may further comprise one or more cytokines. The cytokine may be, for example, any one or a combination of the following: IL-1, IL-4, IL-5, IL-6, IL-9, IL-13, IL-18, IL-25, IFN-α, IFN-β, etc.

[0095] If desired, the stent may also include 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, decefotaxime, cefotaxime, cefoperazone), penicillins (e.g., amoxicillin, amoxicillin with clavulanate, ampicillin, piperacillin, and ticarcillin), optionally with β-lactamase inhibitors (e.g., sulfaquinoxaline, tazobactam, and clavulanic acid), such as ampicillin-sulbactam, piperacillin-tazobactam, and ticarcillin with clavulanate. acid salts, aminoglycosides (e.g., amikacin, abicacin, gentamicin, kanamycin, neomycin, netilmicin, paromycin, rhodamine, streptomycin, tobramycin and doxorubicin), osmotic agents or carbopols (e.g., doripenem, ertapenem, imipenem and meropenem), monobactams (e.g., aztreonam), oxazolidinones (e.g., linezolid), vancomycin, glycopeptide antibiotics (e.g., telavancin), Mycobacterium tuberculosis antibiotics, etc.

[0096] The stent composition may also include one or more antimicrobial agents, including antibacterial agents, antifungal agents (e.g., polyene antifungal agents such as amphotericin B; triazole antifungal agents such as itraconazole, ketoconazole, fluconazole, voriconazole, clotrimazole, isoxazole, miconazole and posaconazole; echinacea antifungal agents such as carbomycin, miconazole and anilamycin; imide antifungal agents such as F901318, which inhibits dihydroorotate dehydrogenase), antiviral agents (e.g., oseltamivir, zanamivir, rimantadine, adamantane, ribavirin, ganciclovir, valganciclovir, fosciclovir, cytomegalovirus immune globulin, pleconaril, lupintravir, palivizumab, moazolizumab, cytarabine, docosanol, denotivir, cidofovir and acyclovir), antiparasitic agents, or combinations thereof.

[0097] The scaffold composition may also include one or more pro-angiogenic (eg, VEGF, PlGF) bioactive molecules to promote vascularization in patients with or without impaired vascular function.

[0098] The scaffold composition may also include one or more anti-fibrotic molecules (anti-TGFβ, anti-TNF-α), such as to reduce fibrosis in the patient at the implantation site.

[0099] The scaffold composition may also include one or more factors that affect adipogenesis and proliferation (eg, IGF-1, dexamethasone) to promote the growth of transplanted adipocytes.

[0100] III. How to use

[0101] The present disclosure includes scaffold compositions and methods for any kind of tissue care, including treatment of wounds, diseased tissues, or any kind of medical conditions that affect the location of soft tissues in the body. Although the scaffold can be used for anyone in need, the scaffold can be used for mammals including humans, and humans can contain soft tissues that require scaffolds. Individuals in need can be individuals with soft tissue injuries, illnesses, postoperative treatments, perioperative treatments, gender reassignment, and / or medical conditions that have led to the need to treat soft tissues. The wound can be internal or external, and can be caused by trauma, disease, tearing, impaired circulation, neuropathy, surgery, etc. Surgery or postoperative treatment may require the use of a scaffold, such as due to obstetric surgery or procedures, male-to-female sex reassignment surgery, breast reconstruction, hernia repair, etc. In some cases, the scaffold can be used for reconstruction or cosmetic purposes.

[0102] The stent may be readily available, or may be manufactured when the stent is needed. In either case, the type of stent needed and / or the size of the individual receiving the stent may be considered before manufacturing or selecting the device. The individual receiving the stent may be a pediatric (up to 12 years old) or adolescent (12-18 years old) or adult. Part or all of the stent may be designed or configured for permanent use, although parts of the stent may be designed or configured to disappear or dissolve over time, including being reabsorbed by the body.

[0103] Partial or complete degradation of the scaffold may or may not coincide with the time of healing. For example, the tissue may heal before partial resorption of the scaffold, or the tissue may not completely heal before partial resorption of the scaffold, and then additional treatment may be used if necessary.

[0104] Specific examples of uses of the device include those for post-surgical, post-surgical and / or post-radiation settings, such as to promote wound healing or prevent scarring or obstruction. In any case, specific examples include at least treatment following radiation and / or surgery, fibrosis of any kind or degree and including treatment or prevention, post-surgical treatment, physical damage or injury, shortening and / or tightening of tissue due to surgery and / or radiation, cervical insufficiency, vaginal / uterine prolapse, or combinations thereof.

[0105] The present disclosure provides a method for enhancing soft tissue in an individual in need, which method may include applying an effective amount of a support to one or more soft tissue sites of an individual. As an example, the soft tissue may include muscle, tendon, ligament, fascia, fat, skin, nerve, blood vessel, or a combination thereof. The soft tissue may include injury, surgical site, birth deformity, pathological tissue, or a combination thereof. In particular, the soft tissue may belong to 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.

[0106] The stent can be applied to the soft tissue of an individual in any suitable manner. The application may include fixing the stent to the soft tissue of the individual and / or fixing the stent to the tissue adjacent to the soft tissue of the individual. The fixation may include suturing, stapling and / or using surgical glue to fix the stent to the soft tissue of the individual and / or the tissue adjacent to the soft tissue of the individual. The wound or gap to be repaired (or both in the same tissue) may determine the type of fixation, and if suturing occurs, the suturing may be a purse string suturing, a continuous suturing, an interrupted suturing, an embedded suturing, a deep suturing or a subcutaneous suturing, as an example. The suture used for suturing may be absorbable or may be non-absorbable.

[0107] IV. Manufacturing Method

[0108] The manufacture of the scaffold may at least in part comprise a series of ordered actions. The method may generally comprise the production of the scaffold by a bioprinter (synthetic polymer), which is performed separately from the preparation of one or more ECM materials (natural polymers, including those utilizing collagen in at least some cases), which are then combined with a cross-linking agent. After the combination of the synthetic polymer and the natural polymer, the combination is subjected to an effective amount of a cross-linking agent, followed by washing (optional) and then freeze drying.

[0109] Methods for producing scaffolds encompassed by the present disclosure may include: (a) three-dimensionally printing a scaffold as a patterned polymer substrate; (b) applying one or more ECM materials to the substrate; (c) subjecting the substrate to one or more cross-linking agents; (d) optionally washing the substrate; and (e) subjecting the substrate to freeze-drying conditions, such as a temperature below 15°C, optionally wherein the one or more ECM materials and the one or more cross-linking agents are mixed together prior to application to the substrate.

[0110] The scaffold can be bioprinted using a suitable synthetic biodegradable polymer such as PCL, PDO, or a combination thereof. Bioprinting of the polymer can follow a specific pattern to produce a unit cell structure that is generally formed as a filament outline that is shaped like an "I" with similarly shaped

[0111] The line width of the filaments can be optimized and can be about 400 μm for PCL and about

[0112] 500 μm. As a separate action, one or more ECM materials (again, in some cases, natural polymers) are prepared or obtained and can be mixed with an effective amount of a cross-linking agent (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) to produce a coating for the stent. Thereafter, the coating mixture to be imparted to the stent is applied to the stent in any suitable manner, such as, immersing the stent in the coating solution, placing the stent on top of the coating solution, spraying the coating onto the stent, dripping the stent onto the coating, or placing the coating onto a substrate.

[0113] Application of one or more ECM materials and / or one or more cross-linking agents may be performed for any suitable amount of time, such as 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours or 24 hours. The application can be performed for 1-24 hours, 1-18 hours, 1-12 hours, 1-10 hours, 1-8 hours, 1-6 hours, 1-2 hours, 2-24 hours, 2-18 hours, 2-16 hours, 2-12 hours, 2-10 hours, 2-8 hours, 2-6 hours, 2-3 hours, 4-24 hours, 4-20 hours, 4-18 hours, 4-12 hours, 4-10 hours, 4-8 hours, 4-6 hours, 6-24 hours, 6-20 hours, 6-18 The application may be cross-linked to the polymer scaffold. The final concentration of the ECM material in the applied solution may be about 0.5 weight / volume %, 0.6 weight / volume %, 0.7 weight / volume %, 0.8 weight / volume %, 0.9 weight / volume %, 1 weight / volume %, 1.1 weight / volume %, 1.2 weight / volume %, 1.3 weight / volume %, 1.4 weight / volume %, or 1.5 weight / volume %. The final concentration of the ECM material in the solution may range from about 0.5% w / v to 1.5% w / v, 0.5% w / v to 1.2% w / v, 0.5% w / v to 1% w / v, 0.5% w / v to 0.07% w / v, 0.07% w / v to 1.5% w / v, 0.07% w / v to 1.2% w / v, 0.07% w / v to 1% w / v, 1% w / v to 1.5% w / v, 1% w / v to 1.2% w / v, or 1.2% w / v to 1.5% w / v.The final concentration of the cross-linking agent in the solution to be applied may 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%. The final concentration of the cross-linking agent in the solution may range from about 0.05% to 0.2% v / v, 0.05% to 0.15% v / v, 0.05% to 0.1% v / v, 0.07% to 0.2% v / v, 0.07% to 0.1% v / v, or 0.1% to 0.2% v / v.

[0114] Once cross-linking is complete, excess coating solution can be washed off the stent substrate (e.g., in any type of water, including triple 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 times, 1-8 times, 1-6 times, 1-4 times, 1-2 times, 2-10 times, 2-8 times, 2-6 times, 2-4 times, 4-10 times, 4-8 times, 4-6 times, 6-10 times, 6-8 times, or 8-10 times to remove residual cross-linking agents contained in the stent. Residual cross-linking agents can cause toxicity in the human body, and no more than 2 ppm of residual cross-linking agents may be present in the stent. Washing can be performed for about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours. Washing can be performed for 1-24 hours, 1-18 hours, 1-12 hours, 1-10 hours, 1-8 hours, 1-6 hours, 1-2 hours, 2-24 hours, 2-18 hours, 2-16 hours, 2-12 hours, 2-10 hours, 2-8 hours, 2-6 hours, 2-3 hours, 4-24 hours, 4-20 hours, 4-18 hours, 4-12 hours, 4-10 hours, 4-8 hours, 4-6 hours, 6-24 hours, 6-20 hours, 6-18 hours. Hours, 6-12 hours, 6-10 hours, 6-8 hours, 8-24 hours, 8-20 hours, 8-18 hours, 8-16 hours, 8-12 hours, 8-10 hours, 10-24 hours, 10-18 hours, 10-16 hours, 10-12 hours, 12-24 hours, 12-18 hours, 12-16 hours, 16-24 hours, 16-20 hours, 16-18 hours, 18-24 hours, 18-20 hours or 20-24 hours. After washing, the scaffold is subjected to freeze drying. This may be done for about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours or more.Freeze drying can be performed for 1-24 hours, 1-18 hours, 1-12 hours, 1-10 hours, 1-8 hours, 1-6 hours, 1-2 hours, 2-24 hours, 2-18 hours, 2-16 hours, 2-12 hours, 2-10 hours, 2-8 hours, 2-6 hours, 2-3 hours, 4-24 hours, 4-20 hours, 4-18 hours, 4-12 hours, 4-10 hours, 4-8 hours, 4-6 hours, 6-24 hours, 6-20 hours, 6-1 8 hours, 6-12 hours, 6-10 hours, 6-8 hours, 8-24 hours, 8-20 hours, 8-18 hours, 8-16 hours, 8-12 hours, 8-10 hours, 10-24 hours, 10-18 hours, 10-16 hours, 10-12 hours, 12-24 hours, 12-18 hours, 12-16 hours, 16-24 hours, 16-20 hours, 16-18 hours, 18-24 hours, 18-20 hours or 20-24 hours. The manufacturing process may include two freeze drying processes, such that the first freeze drying process is performed for the cross-linking process and matrix formulation of the natural polymer, and the second freeze drying process can be performed for re-drying the scaffold after the residual cross-linking agent has been removed.

[0115] One or more therapeutic agents may be used in the scaffold such that the manufacturing method may include applying the one or more therapeutic agents directly or indirectly to part or all of the scaffold. The one or more therapeutic agents may be present in the polymer and 3D printed with the polymer when it is 3D printed; it may be present in the cross-linking solution and / or with one or more ECM materials; a combination of being printed with the polymer and being present in the cross-linking / ECM solution; and / or it may be applied to at least a portion of the outside of the scaffold after the scaffold is manufactured. The therapeutic agent may be manufactured with the scaffold or otherwise placed thereon so that it does not remain on or with the scaffold, but becomes part of the surrounding environment to promote surrounding tissue healing, cell infiltration into the scaffold, cell migration to a wound or diseased site, regeneration of cells or tissue, etc. The manufacturing process considers the concentration of the therapeutic agent used in the scaffold when considering the therapeutically effective amount in the surrounding soft tissue.

[0116] The manufacture of the scaffold can be designed so that the degradation of the scaffold can be adjusted based on at least the concentration of the cross-linking agent, the concentration of the natural polymer decellularized extracellular matrix (dECM) solution, the type of cross-linking agent used, or a combination thereof. For patient needs that require or benefit from a slower degradation rate, a higher concentration of cross-linking agent and / or a longer cross-linking duration can be used during manufacturing. For patient needs that do not require a slower degradation rate, a lower concentration of cross-linking agent can be used. The cross-linking agent concentration used for standard manufacturing practices can be about 0.1%.

[0117] The support can be printed into a limited desired 2D or 3D shape, or each type can be used for a specific soft tissue site in need. The example of the 2D shape printed includes, for example, a line, a curve, a circle, a square, a crescent, a triangle, a rectangle, an ellipse, a trapezoid. The example of a 3D shape includes a sphere, a pyramid, a cube, a cuboid, a cylinder, a cone, a triangular prism, a bowl, or it can be customized to be suitable for a wound or a gap (or both) at a soft tissue site. In some cases, for a 2D shape, the sheet can include one or more marks for one or more of these shapes.

[0118] After manufacturing, the produced stents can be sterilized and packaged to protect them from contamination by external microorganisms or invasion by organisms such as insects. Packaging can also eliminate the risk of pressure or shock in certain environments before use.

[0119] V. Kit

[0120] The present disclosure encompasses kits containing the scaffolds of the present disclosure or compositions for producing the scaffolds of the present disclosure (such as PCL, PDO, both PCL and PDO, one or more cross-linking agents, etc.).

[0121] The kit may include one or more components, any of which may be packaged separately or placed in a container such as a package, tube, bottle, vial, syringe or other suitable container member. The kit may include a scaffold or a composition for producing a scaffold, such as sealed in a package, including sealed in a sterile environment, and the kit may also optionally include one or more therapeutic agents, which are contained in a tube, bottle, vial, syringe, etc. In some cases, one or more therapeutic agents in the kit are contained in one or more compositions to produce the scaffold.

[0122] Individual therapeutic agent components may be provided in a concentrated amount in the kit; a component can be provided alone at the same concentration as it is in solution with the other components. The concentration of a component may be provided, for example, at 1x, 2x, 5x, 10x, or 20x or higher. Examples include at least hormones, antibiotics, analgesics, hemorheology agents, vasoconstrictors, anti-inflammatory agents, antifibrotic agents, wound healing agents, radiation protection materials, antifungal agents, contraceptives, or any combination thereof.

[0123] The kit may be configured to allow placement of the therapeutic agent on the stent at or prior to the point of care.

[0124] VI. Examples

[0125] The following examples are included to illustrate specific compositions and methods of the present disclosure. It will be appreciated by those skilled in the art that the techniques disclosed in the following examples represent techniques that have been found to work well in the practice of the methods and compositions of the present disclosure, and therefore may be considered to constitute specific modes of their practice. However, in view of the present disclosure, it will be appreciated by those skilled in the art that many changes may be made in the specific aspects disclosed without departing from the spirit and scope of the subject matter of the present disclosure and still obtaining the same or similar results.

[0126] Example 1

[0127] Soft tissue augmentation scaffold characterization

[0128] The soft tissue reinforcement scaffold, which may be referred to as a STRS, may be characterized by the following studies.

[0129] The scaffold can maintain one or more desired mechanical properties better than a control for at least a specific period of time, such as at least about 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours or 48 hours, and including at least about 3 days, 4 days, 5 days, 6 days or 7 days, and including at least about 1 week, 2 weeks, 3 weeks or 4 weeks, and including at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months or longer.

[0130] In one example of mechanical properties, hydrolytic degradation can be characterized. The scaffolds were subjected to hydrolytic degradation in PBS at 37°C for 6 weeks. In this test, mechanical properties such as ultimate tensile strength (UTS) and Young's modulus (YM) were observed, and microscopic images of the degradation were taken at the following time points: week 0 and week 6. The control group used was polyglactin 910 mesh (longitudinal direction), and the test scaffold was polycaprolactone (PCL) STRS.

[0131] exist Figure 2 The microscopic results are provided in. The PCL STRS structure maintained its original shape at week 6. However, the structure of the polyglactin 910 mesh was not maintained at the same time point. Figure 3A and Figure 3B The degradation profile of polyglactin 910 NET is provided, and Figure 4A and Figure 4BDegradation curves of PCL STRS structures are provided. In the case of polyglactin 910 mesh, both UTS and YM were considered to be 0 at week 6 because they could not be measured (UTS, YM reduction rate (%) = 100). However, PCL STRS maintained sufficient UTS and YM for 6 weeks after the degradation experiment. Therefore, this confirms that PCL STRS can meet an example of critical quality (CTQ) standards and PCL is an appropriate material for manufacturing STRS.

[0132] An example of characterization of the biological components of STRS: enzymatic degradation. A porcine non-cross-linked extracellular collagen matrix was used as a control group for enzymatic degradation testing, and the degradation period between the porcine non-cross-linked extracellular collagen matrix and collagen matrices prepared with different concentrations of the cross-linking agent 1,4-butanediol diglycidyl ether (BDDE) using the same units of collagenase was compared. Figure 5 The results of the degradation curves of the porcine non-crosslinked extracellular collagen matrix and the natural polymer matrix produced using different concentrations of BDDE are shown. The enzymatic degradation test was performed using 100 U of collagenase, and the values ​​of the porcine non-crosslinked extracellular collagen matrix are the averages of two different batches. The total sample size of XCM was nine, and the sample size of BDDE concentration was five.

[0133] Comparing the degradation curves, the matrix with a concentration of 0.06% BDDE has a faster degradation curve than the porcine non-cross-linked extracellular collagen matrix, and the matrix with a concentration of 0.1% BDDE has a degradation curve similar to the porcine non-cross-linked extracellular collagen matrix. Finally, the matrix with a concentration of 0.2% BDDE has a slower biodegradation period than the porcine non-cross-linked extracellular collagen matrix. As for the biodegradation period, as an example, 0.1% BDDE and 0.2% BDDE can be used.

[0134] BDDE is a cytotoxic substance that can cause side effects in the human body, and the amount of residual BDDE can be controlled to less than 2 ppm (the maximum acceptable value according to FDA requirements), and can be used as little as possible in consideration of safety. In addition, the cleaning process that meets the standard may vary depending on the concentration of BDDE used initially. Taking various factors into consideration, a 0.1% concentration of BDDE having the same degradation curve as the porcine-derived non-cross-linked extracellular collagen matrix is ​​selected, and as an example, the number of washes for the cleaning process for STRS is set to 5 times.

[0135] Figure 6A UTS graph comparing a test STRS to a commercial product, MegaDerm (L&C BIO), an acellular dermal matrix (ADM) control, and a TnR mesh (T&R Biofab) is provided. The test STRS, having a unit structure pattern covered by the claims (generally similar to a unit structure of an "I"), is compared to a product (TnR mesh) having the same material but a different unit structure pattern. Clearly, the test STRS has a curve that is more similar to the MegaDerm curve (ADM control) over the first 2 mm of the graph. This curve similarity indicates that the STRS product performs closer to the ADM control and is therefore more easily substituted for it.

[0136] Example 2

[0137] Cell infiltration

[0138] STRS was compared with ADM products in terms of their ability to be infiltrated by cell growth. Figure 7 In the case of the representative ADM sample provided in the H&E staining image of the product, cells were unable to penetrate the product due to the detailed internal structure of the product itself. However, in the case of the STRS product, the STRS product was manufactured with a structure that allowed cells to infiltrate the construct, and Figure 7 This is confirmed by the image of in vitro testing on the right, which shows that when the product is transplanted into an individual, the cells easily penetrate and self-organize.

[0139] Example 3

[0140] Degradation control

[0141] STRS products may include natural polymers. In this case, the degradation period of the natural polymer can be controlled by adjusting the concentration of the cross-linking agent. When compared with ADM, STRS products may have similar, higher or lower degradation resistance, which is confirmed by in vitro collagenase degradation tests ( Figure 8 ). This indicates that the physical properties of the product can be adjusted according to the instructions for using the product.

[0142] Example 4

[0143] Fabrication of STRS

[0144] A demonstrative example of the overall STRS manufacturing process is provided. The manufacturing process is designed to consider: performance factors such as tensile strength and strain; stability, such as thermal stability and solvent resistance; and printability (having a print head speed that can be produced). The synthetic polymers are examined based on each detailed factor. The results of testing various synthetic polymers are that polycaprolactone and polydioxanone are selected for further characterization. Various pattern design candidates are selected for STRS manufacturing, some of which have similar UTS and SUTS values ​​as ADM and similar stress-strain curves. As a result of tensile testing using these polymers, a final pattern with a much lower UTS value than ADM was selected, which is a pattern with a unit pattern that is generally "I" shaped. After UTS analysis of multiple unit patterns according to different line widths, and considering the texture of the scaffold, for PCL, a line width (LW) of approximately 500μm and a pattern density of 18ea / cm can be utilized. 2 STRS, and / or for PDO, a line width (LW) of 400 μm and a pattern density of 25 ea / cm 2 of STRS.

[0145] STRS were fabricated using an inlay approach, with multilayer scaffolds (0.2 mm scaffold × 5 sheets) comprising the above PCL (pattern P) and PDO (pattern P) candidates, respectively. This included a tendon decellularized extracellular matrix (dECM) solution as a natural polymer and BDDE as a cross-linking agent. Fig. 9 An example of the entire STRS fabrication process is provided.

[0146] 1. Preparation of Synthetic Polymer Scaffolds

[0147] The scaffolds were fabricated under the conditions described in the previous section.

[0148] 2. Preparation of a mixture of natural polymer and crosslinker

[0149] a) Tendon dECM was placed in 1.2 weight / volume % 0.01N HCl and incubated at 4°C

[0150] Allow it to swell for 4 to 5 hours.

[0151] b) Grind the swollen tendon dECM using a homogenizer.

[0152] (The grinding condition was 6000 rpm, and after grinding for 1 minute, it was placed on ice for 30 seconds to prevent the temperature from rising. This was repeated 5 times in total).

[0153] c) Store the tendon dECM solution at 4°C prior to use and use within 24 hours.

[0154] d) Dilute the 1.2% tendon dECM solution with 0.01N HCl containing BDDE. At this point, mix the final concentration to 1 wt / vol% tendon dECM solution and 0.1 vol / vol% BDDE.

[0155] e) In order to remove air bubbles in the mixture, the mixture was centrifuged at 2000 rpm at 4°C for 5 minutes.

[0156] f) To remove invisible particles, the mixture was filtered through a 500 μm sieve.

[0157] g) To remove air bubbles, repeat the centrifugation process described in item 5.

[0158] 3. Combination of natural and synthetic polymers

[0159] The process involves integrating the prepared scaffolds with a mixture of natural polymers and BDDE as described:

[0160] a) Insert the membrane paper into the lower frame.

[0161] b) Load 5 mL of the prepared mixture onto the membrane paper.

[0162] c) Position the rack (5 separate sheets) over the loaded mixture.

[0163] d) Using a spatula, spread the mixture beneath the multi-layer scaffold to fill all pores of the scaffold.

[0164] e) Place the membrane paper on top of the multi-layer support.

[0165] f) Merge the upper frame to remove the remaining mixture. To ensure uniform thickness of the STRS, the upper frame should be firmly joined to the lower frame.

[0166] 4. Cross-linking (freeze-drying process)

[0167] The natural polymers were integrated with the synthetic polymers while being cross-linked by BDDE. The natural polymers were cross-linked by a freeze-drying process.

[0168] a) Samples prepared in the combination of natural and synthetic polymers were placed in a freeze dryer.

[0169] b) freeze-drying under appropriate conditions. Fig.10 An example is provided in .

[0170] 5. Washing

[0171] This process is to remove the residual cross-linking agent after the cross-linking process of the natural polymer.

[0172] a) After freeze drying is complete, the STRS are separated from the framework.

[0173] b) As shown on the right side of the figure above, place the tray on the orbital shaker and place the STRS inside.

[0174] c) Add 100 mL of distilled water (DW) to each STRS. (STRS is based on 75 mm x 75 mm. If the size increases, the amount of distilled water needs to be adjusted accordingly.)

[0175] d) Spin at 30-50 rpm for 10 minutes at room temperature.

[0176] e) Replace with fresh distilled water and spin and replace with fresh distilled water 5 times.

[0177] 6. Freeze Drying

[0178] a) Place the washed STRS into a frame or plastic container and place it into a freeze dryer.

[0179] b) freeze-drying under suitable conditions (see, for example, Fig.10 ).

[0180] The manufactured STRS product may be packaged and stored, or used substantially immediately.

[0181] Example 5

[0182] Tensile test of the manufactured PCL STRS and PDO STRS

[0183] PCL STRS with a line width of 400 μm and PDO STRS with a line width of 500 μm (each having a generally "I" shaped unit structure) were characterized for tensile strength.

[0184] Tensile tests were performed with three types of STRS prototypes made of scaffolds with line widths of PCL 500 μm and PDO 400 μm, the results of which can be seen in Table 1. As can be seen in the table, for PCL 500 μm, 4.40 MPa was measured, and each STRS had a lower value than the previous synthetic polymer scaffold. However, as can be seen in Table 2, which is the result of the ADM tensile test, PCL 500 μm is higher than MegaDerm and slightly lower than XCM.

[0185] Table 1: Tensile test results and information of STRS

[0186]

[0187] Table 2: ADM tensile test results and information

[0188]

[0189] Fig.11 UTS images of different types and line widths of STRS compared to MegaDerm are provided. PCL STRS with a line width of 400 μm are closer to the ADM control, MegaDerm. Fig.12 Bubble plots of STRS and MegaDerm are provided, also reflecting that the PCL STRS with a line width of 400 μm is closer to the ADM control. Burst tests, tear tests, cell infiltration tests, etc. can be used to further characterize the PCL STRS or PDO STRS.

[0190] VII. Detailed description of implementation scheme

[0191] Embodiment 1. An artificial support structure, comprising one or more biodegradable polymers and one or more extracellular matrix materials, the support structure also comprising: a plurality of unit patterns, each unit pattern comprising a plurality of filaments arranged continuously, symmetrically and regularly thereon, each unit pattern being composed of edges of a closed shape so as to form holes therein, wherein the plurality of unit patterns are connected so as to have intersections with each other, and the number of intersections is the same as the number of edges passing through the intersections.

[0192] Embodiment 2. An artificial support structure according to embodiment 1, wherein the one or more extracellular matrix materials include collagen I.

[0193] Embodiment 3. The artificial support structure according to embodiment 1 or 2, wherein at least one unit pattern has a diameter between about 200 microns and about 3.5 mm.

[0194] Embodiment 4. The artificial support structure according to any one of Embodiments 1 to 3, wherein at least one unit pattern has a diameter between about 1.5 mm and about 3 mm.

[0195] Embodiment 5. The artificial support structure according to any one of embodiments 1 to 4, wherein at least one unit pattern has a diameter between about 1.782 mm and about 2.97 mm.

[0196] Embodiment 6. The 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.

[0197] 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.

[0198] Embodiment 8. The artificial support structure of any one of Embodiments 1 to 7, wherein the plurality of connected unit patterns form a substantially planar sheet.

[0199] Embodiment 9. An artificial support structure according to any one of Embodiments 1 to 8, wherein the plurality of connected unit patterns form a three-dimensional macrostructure.

[0200] Embodiment 10. The artificial support structure of any one of Embodiments 1 to 9, wherein the artificial support structure has a thickness between about 0.5 mm and about 1.5 mm.

[0201] Embodiment 11. An artificial support structure according to any one of Embodiments 1 to 10, wherein the artificial support structure has a thickness between about 0.7 mm and about 1.3 mm.

[0202] Embodiment 12. An artificial support structure according to any one of Embodiments 1 to 11, wherein the artificial support structure has a thickness between about 0.9 mm and about 1.1 mm.

[0203] Embodiment 13. An artificial support structure according to any one of Embodiments 1 to 12, wherein the artificial support structure contains 1 to 5 layers.

[0204] Embodiment 14. The artificial support structure according to embodiment 13, wherein the layer further has a thickness between about 0.10 mm and about 0.3 mm.

[0205] Embodiment 15. The artificial support structure according to embodiment 13 or 14, wherein the layer further has a thickness between 0.15 mm and about 0.25 mm.

[0206] Embodiment 16. The artificial support structure according to any one of Embodiments 13 to 15, wherein the layer further has a thickness between 0.18 mm and about 0.22 mm.

[0207] Embodiment 17. The artificial support structure of any one of Embodiments 1 to 16, wherein one or more of the plurality of filaments has a diameter less than 550 microns.

[0208] Embodiment 18. The artificial support structure of any one of Embodiments 1 to 17, wherein one or more of the plurality of filaments has a diameter less than 500 microns.

[0209] Embodiment 19. The artificial support structure of any one of Embodiments 1 to 18, wherein one or more of the plurality of filaments has a diameter less than 400 microns.

[0210] Embodiment 20. An artificial support according to any one of Embodiments 1 to 19, wherein four unit patterns are connected to have four intersections with each other and have four sides passing through the four intersections, and a space surrounded by the four unit patterns has the same or similar shape as each unit pattern.

[0211] Embodiment 21. The artificial support according to any one of embodiments 1 to 20, wherein each unit pattern is a capital "I" of the English alphabet.

[0212] Embodiment 22. An artificial support according to Embodiment 21, wherein the short sides of the sides of the closed shape of each unit pattern have the same length as each other, and the long sides thereof have the same length as each other, so that the space surrounded by the four unit patterns has the same shape as each unit pattern.

[0213] Embodiment 23. An artificial support according to Embodiment 22, wherein, in the closed shape, the length ratio of the short side to the long side is 1:3.

[0214] Embodiment 24. An artificial support structure according to any one of Embodiments 1 to 23, wherein the artificial support structure has an ultimate tensile strength between about 4 MPa and about 5 MPa.

[0215] Embodiment 25. The artificial support structure of any one of Embodiments 1 to 24, wherein the artificial support structure has an ultimate tensile strength between about 4.05 MPa and about 4.7 MPa.

[0216] Embodiment 26. The artificial support structure of any one of Embodiments 1 to 25, wherein the artificial support structure has an ultimate tensile strength between about 4.12 MPa and about 4.50 MPa.

[0217] Embodiment 27. An 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.

[0218] Embodiment 28. An 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.

[0219] 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.

[0220] Embodiment 30. An artificial support structure according to any one of Embodiments 1 to 29, wherein the artificial support structure has a suture holding strength of about 20N to about 26N.

[0221] Embodiment 31. An artificial support structure according to any one of Embodiments 1 to 30, wherein the artificial support structure has a suture holding strength of about 21N to about 25N.

[0222] Embodiment 32. An artificial support structure according to any one of Embodiments 1 to 31, wherein the artificial support structure has a suture holding strength of about 22.03N to about 24.27N.

[0223] Embodiment 33. An artificial support structure according to any one of Embodiments 1 to 32, wherein the artificial support structure has a burst strength of about 140N to about 170N.

[0224] Embodiment 34. An artificial support structure according to any one of Embodiments 1 to 33, wherein the artificial support structure has a burst strength of about 145N to about 163N.

[0225] Embodiment 35. An artificial support structure according to any one of Embodiments 1 to 34, wherein the artificial support structure has a burst strength of about 147.14N to about 161.26N.

[0226] Embodiment 36. An artificial support structure according to any one of Embodiments 1 to 35, wherein the artificial support structure has a tear resistance of about 18N to about 26N.

[0227] Embodiment 37. An artificial support structure according to any one of Embodiments 1 to 36, wherein the artificial support structure has a tear resistance of about 19N to about 25N.

[0228] Embodiment 38. An artificial support structure according to any one of Embodiments 1 to 37, wherein the artificial support structure has a tear resistance of about 19.87N to about 24.92N.

[0229] Embodiment 39. An artificial support structure, comprising one or more biodegradable polymers and one or more extracellular matrix materials, the support structure also comprising: a plurality of unit patterns, each unit pattern comprising a plurality of filaments repeatedly arranged to form columns or rows symmetrical to each other, each unit pattern being composed of edges of a closed shape to thereby form holes therein, wherein the columns or rows along which the plurality of unit patterns are repeatedly arranged have Euler trajectories.

[0230] Embodiment 40. An artificial support structure according to Embodiment 39, wherein the one or more extracellular matrix materials include collagen I.

[0231] Embodiment 41. An artificial support structure according to embodiment 39 or 40, wherein at least one unit pattern has a diameter between about 200 microns and about 3.5 mm.

[0232] Embodiment 42. An artificial support structure according to Embodiment 41, wherein at least one unit pattern has a diameter between about 1.5 mm and about 3 mm.

[0233] Embodiment 43. An artificial support structure according to Embodiment 42, wherein at least one unit pattern has a diameter between about 1.782 mm and about 2.97 mm.

[0234] Embodiment 44. The 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.

[0235] 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.

[0236] Embodiment 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.

[0237] Embodiment 47. An artificial support structure according to any one of Embodiments 39 to 46, wherein the plurality of connected unit patterns form a three-dimensional macrostructure.

[0238] Embodiment 48. An artificial support structure according to embodiments 39 to 47, wherein the artificial support structure has a thickness between about 0.5 mm and about 1.5 mm.

[0239] Embodiment 49. An artificial support structure according to any one of Embodiments 39 to 48, wherein the artificial support structure has a thickness between about 0.7 mm and about 1.3 mm.

[0240] Embodiment 50. An artificial support structure according to any one of Embodiments 39 to 40, wherein the artificial support structure has a thickness between about 0.9 mm and about 1.1 mm.

[0241] Embodiment 51. An artificial support structure according to any one of Embodiments 39 to 50, wherein the artificial support structure contains 1 to 5 layers.

[0242] Embodiment 52. An artificial support structure according to Embodiment 51, wherein the layer further has a thickness between about 0.10 mm and about 0.3 mm.

[0243] Embodiment 53. An artificial support structure according to any one of Embodiments 51 or 52, wherein the layer further has a thickness between 0.15 mm and about 0.25 mm.

[0244] Embodiment 54. The artificial support structure according to any one of Embodiments 51 to 53, wherein the layer further has a thickness between 0.18 mm and about 0.22 mm.

[0245] Embodiment 55. An artificial support structure according to any one of Embodiments 39 to 54, wherein one or more filaments of the plurality of filaments have a diameter less than 550 mm.

[0246] Embodiment 56. An artificial support structure according to any one of Embodiments 39 to 55, wherein one or more filaments of the plurality of filaments have a diameter less than 500 mm.

[0247] Embodiment 57. An artificial support structure according to any one of Embodiments 39 to 56, wherein one or more filaments of the plurality of filaments have a diameter less than 400 mm.

[0248] Embodiment 58. An artificial support according to any one of Embodiments 39 to 57, wherein the columns or rows along which the plurality of unit patterns are repeatedly arranged are connected to allow the plurality of unit patterns to have intersections with the plurality of unit patterns of adjacent columns or rows.

[0249] Embodiment 59. The artificial support according to Embodiment 58, wherein the number of intersections of the plurality of unit patterns is the same as the number of edges passing through the intersections.

[0250] Embodiment 60. The artificial support according to Embodiment 59, wherein four adjacent unit patterns are connected to have four intersections with each other and have four sides passing through the four intersections, and a space surrounded by the four unit patterns has the same or similar shape as that of each unit pattern.

[0251] Embodiment 61. The artificial support according to any one of embodiments 39 to 60, wherein each unit pattern is a capital "I" of the English alphabet.

[0252] Embodiment 62. An artificial support according to Embodiment 61, wherein the short sides of the sides of the closed shape of each unit pattern have the same length as each other, and the long sides thereof have the same length as each other, so that the space surrounded by the four unit patterns has the same shape as each unit pattern.

[0253] Embodiment 63. An artificial support according to Embodiment 62, wherein, in the closed shape, the ratio of the length of the short side to the long side is 1:3.

[0254] Embodiment 64. An artificial support according to Embodiment 63, wherein, in the closed shape, the ratio of the length of each short side to each long side is 1:3.

[0255] Embodiment 65. An artificial support according to Embodiment 64, wherein the plurality of unit patterns in a column or row along which the plurality of unit patterns are repeatedly arranged have an angle of 45° or 135° relative to the row or column.

[0256] Embodiment 66. The artificial support according to Embodiment 65, wherein portions of the edges of the plurality of unit patterns are regularly arranged to form edges of the artificial support.

[0257] Embodiment 67. An artificial support structure according to any one of Embodiments 39 to 66, wherein the artificial support has an ultimate tensile strength between about 4.05 MPa and about 4.7 MPa.

[0258] Embodiment 68. An artificial support structure according to any one of Embodiments 39 to 67, wherein the artificial support has an ultimate tensile strength between about 4.12 MPa and about 4.50 MPa.

[0259] Embodiment 69. An artificial support structure according to 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.

[0260] Embodiment 70. An artificial support structure according to 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.

[0261] Embodiment 71. An artificial support structure according to 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.

[0262] Embodiment 72. An artificial support structure according to any one of Embodiments 39 to 71, wherein the artificial support structure has a suture holding strength of about 20N to about 26N.

[0263] Embodiment 73. An artificial support structure according to any one of Embodiments 39 to 72, wherein the artificial support structure has a suture holding strength of about 21N to about 25N.

[0264] Embodiment 74. An artificial support structure according to any one of Embodiments 39 to 73, wherein the artificial support structure has a suture retention strength of about 22.03N to about 24.27N.

[0265] Embodiment 75. An artificial support structure according to any one of Embodiments 39 to 74, wherein the artificial support structure has a burst strength of about 140N to about 170N.

[0266] Embodiment 76. An artificial support structure according to any one of Embodiments 39 to 75, wherein the artificial support structure has a burst strength of about 145N to about 163N.

[0267] Embodiment 77. An artificial support structure according to any one of Embodiments 39 to 76, wherein the artificial support structure has a burst strength of about 147.14N to about 161.26N.

[0268] Embodiment 78. An artificial support structure according to any one of Embodiments 39 to 77, wherein the artificial support structure has a tear resistance of about 18N to about 26N.

[0269] Embodiment 79. An artificial support structure according to any one of Embodiments 39 to 78, wherein the artificial support structure has a tear resistance of about 19N to about 25N.

[0270] Embodiment 80. An artificial support structure according to any one of Embodiments 39 to 79, wherein the artificial support structure has a tear resistance of about 19.87N to about 24.92N.

[0271] Embodiment 81. A support comprising a patterned polymer substrate having a coating of one or more extracellular matrix (ECM) materials thereon, wherein the pattern of the polymer substrate comprises a series of adjacent rows of unit cell structures, each unit cell structure being generally in the shape of the letter "I", the unit cell structures being arranged in the rows of the patterned polymer substrate in a vertical alternating pattern of the unit cell structures.

[0272] Embodiment 82. A support according to embodiment 81, wherein the unit cell structures in the series are further defined as including holes formed as center lines, the length of the center lines being greater than the length of two lines of substantially equal length each perpendicular to opposite ends of the center lines, and wherein the alternating pattern is configured so that each of the ends of the center lines of the holes are generally perpendicular to the center lines of the holes of adjacent unit cell structures.

[0273] Embodiment 83. A support according to embodiment 81 or 82, wherein the support is configured as one or more sheets, each sheet comprising a first planar side and a second planar side.

[0274] Embodiment 84. A support according to embodiment 83, wherein the support comprises 1, 2, 3, 4 or 5 sheets, or comprises at least or no more than 1, 2, 3, 4 or 5 sheets.

[0275] Embodiment 85. A bracket according to embodiment 83 or 84, wherein the plurality of sheets are configured such that a planar side of one sheet is adjacent to a planar side of another sheet.

[0276] Embodiment 86. A bracket according to any one of Embodiments 82 to 85, wherein the bracket comprises one or more defined shapes.

[0277] Embodiment 87. A bracket according to embodiment 86, wherein the defined shape is generally a line, a curve, a circle, a square, a crescent, a triangle, a rectangle, an ellipse, a trapezoid, or wherein the bracket includes markings for one or more of the defined shapes.

[0278] Embodiment 88. The stent of any one of Embodiments 81 to 87, wherein the polymer matrix comprises polycaprolactone, polydioxanone, or a combination thereof.

[0279] Embodiment 89. The stent of any one of Embodiments 81 to 88, wherein the polymer matrix is ​​composed of polycaprolactone.

[0280] Embodiment 90. A scaffold according to any one 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.

[0281] Embodiment 91. A scaffold according to embodiment 90, wherein the collagen is derived from tendon, rat tail, bovine, porcine, or is recombinant.

[0282] Embodiment 92. A scaffold according to embodiment 90 or 91, wherein the combination of one or more types of collagen includes type I collagen and type III collagen.

[0283] Embodiment 93. A scaffold according to embodiment 92, wherein the collagen is atelopeptide collagen derived from bovine tendon, rat tail tendon, or is recombinant.

[0284] Embodiment 94. A stent according to any one of Embodiments 81 to 93, wherein the coating is contained 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.

[0285] Embodiment 95. The stent of any one of Embodiments 81 to 94, wherein the coating fills the pores of the plurality of unit cell structures of the stent.

[0286] Embodiment 96. The stent of any one of Embodiments 81 to 95, wherein the coating fills a majority of the pores of the unit cell structure of the stent.

[0287] Embodiment 97. The stent of any one of Embodiments 81 to 96, wherein the coating fills the pores of substantially all of the unit cell structures of the stent.

[0288] Embodiment 98. The stent of any one of Embodiments 81 to 97, wherein the coating does not fill the pores of a majority of the unit cell structure of the stent.

[0289] Embodiment 99. The stent of any one of Embodiments 81 to 98, wherein the coating does not fill the pores of substantially all of the unit cell structures of the stent.

[0290] Embodiment 100. A bracket according to any one of Embodiments 81 to 99, wherein the thickness of the bracket is no greater than 1 mm.

[0291] Embodiment 101. A stent according to any one of Embodiments 81 to 100, wherein the stent further comprises one or more therapeutic agents.

[0292] Embodiment 102. The stent 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.

[0293] Embodiment 103. A method for producing a scaffold according to any one of embodiments 81 to 102, the 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 washing the substrate; and (e) subjecting the substrate to a temperature below 15°C, optionally wherein the one or more ECM materials and the one or more cross-linking agents are mixed together before being applied to the substrate.

[0294] Embodiment 104. The method of Embodiment 103, wherein the polymer substrate is composed of polycaprolactone, polydioxanone, or a combination thereof.

[0295] Embodiment 105. The method of Embodiment 103 or 104, wherein the applying comprises immersing the substrate in a solution of the coating.

[0296] Embodiment 106. The method of any one of Embodiments 103 to 105, wherein the applying comprises placing the substrate on top of a solution of the coating.

[0297] Embodiment 107. The method of any one of Embodiments 103 to 106, wherein the applying comprises spraying, dripping, or placing the coating on the substrate.

[0298] Embodiment 108. The method of any one of Embodiments 107 to 111, wherein the applying is performed for 1 hour to 24 hours, 5 hours to 24 hours, 5 hours to 20 hours, 8 hours to 20 hours, 8 hours to 15 hours, or 9 hours to 11 hours.

[0299] Embodiment 109. The method of any one of Embodiments 103 to 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.

[0300] Embodiment 110. The method of any one of Embodiments 103 to 109, wherein (c) is performed for about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours.

[0301] Embodiment 111. The method of any one of Embodiments 103 to 110, wherein the washing is performed with water.

[0302] Embodiment 112. The method of any one of Embodiments 103 to 111, wherein (d) is performed for about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours.

[0303] Embodiment 113. The method of any one of Embodiments 103 to 112, wherein (e) is performed for about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours.

[0304] Embodiment 114. The method according to any one of Embodiments 103 to 113, wherein after (e), the produced scaffold is subjected to drying.

[0305] Embodiment 115. The method of any one of Embodiments 103 to 114, further comprising applying one or more therapeutic agents to the stent.

[0306] Embodiment 116. A method according to 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 outside of the stent.

[0307] Embodiment 117. The method of any one of Embodiments 103 to 116, wherein the degradation of the patterned polymer substrate can be regulated based on the concentration of the crosslinking agent.

[0308] Embodiment 118. The method of any one of Embodiments 103 to 117, comprising washing the substrate after subjecting the substrate to one or more cross-linking agents.

[0309] Embodiment 119. A method according to any one of Embodiments 103 to 117, wherein the stent is produced into a defined shape.

[0310] Embodiment 120. A method according to embodiment 119, wherein the defined shape is configured based on formation through a mandrel, or is a pre-programmed macrostructure of 3D printing.

[0311] Embodiment 121. A method of enhancing soft tissue in an individual in need thereof, the method comprising applying an effective amount of a scaffold according to any one of Embodiments 1 to 102 to one or more soft tissue sites of the individual.

[0312] Embodiment 122. A method according to embodiment 121, wherein the soft tissue comprises muscle, tendon, ligament, fascia, fat, skin, nerve, blood vessel or a combination thereof.

[0313] Embodiment 123. A method according to embodiment 121 or 122, wherein the soft tissue comprises an injury, a surgical site, a birth malformation, a diseased tissue, or a combination thereof.

[0314] Embodiment 124. The method of any one of Embodiments 121 to 123, wherein the soft tissue is 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.

[0315] Embodiment 125. A method according to any one of Embodiments 121 to 124, wherein the soft tissue comprises breast tissue for breast reconstruction, breast reduction or breast augmentation.

[0316] Embodiment 126. A method according to any one of Embodiments 121 to 125, wherein the soft tissue comprises a hernia.

[0317] Embodiment 127. A method according to any one of Embodiments 121 to 126, wherein the applying comprises fixing the stent to the soft tissue of the individual and / or tissue of the individual adjacent to the soft tissue.

[0318] Embodiment 128. A method according to Embodiment 127, wherein the fixation is further defined as suturing, stapling or using surgical glue to fix the support to the soft tissue of the individual and / or tissue of the individual adjacent to the soft tissue.

[0319] Embodiment 129. A method according to embodiment 128, wherein the suture is a purse string suture, a continuous suture, an interrupted suture, a buried suture, a deep suture or a subcutaneous suture.

[0320] Embodiment 130. A method according to embodiment 128 or 129, wherein the suture of the suturing is absorbable.

[0321] Embodiment 131. A method according to embodiment 129 or 130, wherein the suture of the suturing is non-absorbable.

[0322] 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 arranged in a series of adjacent rows of vertically alternating unit cell structures, each unit cell structure generally comprising a hole shaped to have a center line, the length of the center line being greater than the length of two lines of substantially equal length each perpendicular to opposite ends of the center line, wherein the alternating pattern is configured such that each of the ends of the center line of the hole is generally perpendicular to the center line of the hole of an adjacent unit cell structure.

[0323] Embodiment 133. The flexible sheet of Embodiment 132, wherein the unit cell structure is composed of one or more biodegradable polymers.

[0324] Embodiment 134. The flexible sheet of Embodiment 132 or 133, wherein the sheet comprises a coating of one or more ECM materials.

[0325] Embodiment 135. The pliable sheet of Embodiment 134 is further defined as a unit cell structure comprising a coating of one or more ECM materials.

[0326] Embodiment 136. The flexible sheet of any one of Embodiments 132 to 135, wherein the pores are filled with the coating.

[0327] Embodiment 137. The flexible sheet of any one of Embodiments 132 to 136, wherein the one or more ECM materials comprise type I collagen.

[0328] Embodiment 138. The flexible sheet according to any one of Embodiments 132 to 137, contained in a suitable package.

[0329] ***

[0330] All methods disclosed and claimed herein can be carried out and performed without undue experimentation in accordance with the present disclosure. Although the compositions and methods of the present invention have been described according to preferred embodiments, it is apparent to those skilled in the art that the methods and steps or step sequences of the methods described herein can be changed without departing from the concept, spirit and scope of the present invention. More specifically, it is apparent that certain reagents related to chemistry and physiology can replace the reagents described herein while achieving the same or similar results. All such similar substitutions and modifications apparent to those skilled in the art are considered to fall within the spirit, scope and concept of the disclosed subject matter as defined by the appended claims.

Claims

1. An artificial support structure, comprising one or more biodegradable polymers and one or more extracellular matrix materials, the support structure further comprising: a plurality of unit patterns, each unit pattern comprising a plurality of filaments arranged continuously, symmetrically and regularly thereon, each unit pattern being constituted by sides of a closed shape to thereby form a hole therein, The plurality of unit patterns are connected to thus have intersections with each other, and the number of the intersections is the same as the number of sides passing through the intersections.

2. An artificial support structure according to claim 1, wherein the one or more extracellular matrix materials include collagen I.

3. The artificial support structure according to any one of the preceding claims, wherein at least one unit pattern has a diameter between about 200 microns and about 3.5 mm.

4. The artificial support structure according to any one of the preceding claims, wherein at least one unit pattern has a diameter between about 1.5 mm and about 3 mm.

5. The artificial support structure according to any one of the preceding claims, wherein at least one unit pattern has a diameter between about 1.782 mm and about 2.97 mm.

6. The artificial support structure according to any one of claims 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 the preceding claims, wherein the one or more extracellular matrix materials is collagen I.

8. An artificial support structure according to any one of the preceding claims, wherein the plurality of connected unit patterns form a substantially planar sheet.

9. The artificial support structure according to any one of the preceding claims, wherein the plurality of connected unit patterns form a three-dimensional macrostructure.

10. The artificial support structure according to any one of the preceding claims, wherein the artificial support structure has a thickness between about 0.5 mm and about 1.5 mm.

11. The artificial support structure according to any one of the preceding claims, wherein the artificial support structure has a thickness between about 0.7 mm and about 1.3 mm.

12. The artificial support structure according to any one of the preceding claims, wherein the artificial support structure has a thickness between about 0.9 mm and about 1.1 mm.

13. The artificial support structure according to any one of the preceding claims, wherein the artificial support structure contains 1 to 5 layers.

14. The artificial support structure of claim 13, wherein the layer further has a thickness between about 0.10 mm and about 0.3 mm.

15. The artificial support structure according to claim 13 or 14, wherein the layer further has a thickness between 0.15 mm and about 0.25 mm.

16. The artificial support structure according to any one of claims 13 to 15, wherein the layer further has a thickness between 0.18 mm and about 0.22 mm.

17. An artificial support structure according to any one of the preceding claims, wherein one or more filaments of the plurality of filaments have a diameter of less than 550 microns.

18. An artificial support structure according to any one of the preceding claims, wherein one or more filaments of the plurality of filaments have a diameter of less than 500 microns.

19. An artificial support structure according to any one of the preceding claims, wherein one or more of the plurality of filaments has a diameter of less than 400 microns.

20. The artificial support according to any one of the preceding claims, wherein four unit patterns are connected to have four intersections with each other and have four sides 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 according to any one of the preceding claims, wherein each unit pattern is a capital "I" of the English alphabet.

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

23. The artificial support according to claim 22, wherein: In the closed shape, a length ratio of the short side to the long side is 1:

3.

24. The artificial support structure of any one of the preceding claims, wherein the artificial support structure has an ultimate tensile strength between about 4 MPa and about 5 MPa.

25. The artificial support structure of any one of the preceding claims, wherein the artificial support structure has an ultimate tensile strength between about 4.05 MPa and about 4.7 MPa.

26. The artificial support structure of any one of the preceding claims, wherein the artificial support structure has an ultimate tensile strength between about 4.12 MPa and about 4.50 MPa.

27. The artificial support structure according to any one of the preceding claims, wherein the artificial support structure has an elastic modulus of about 2.8 MPa to about 4.2 MPa.

28. The artificial support structure of any one of the preceding claims, 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 the preceding claims, wherein the artificial support structure has an elastic modulus of about 3.06 MPa to about 4.00 MPa.

30. The artificial support structure of any one of the preceding claims, wherein the artificial support structure has a suture retention strength of about 20N to about 26N.

31. The artificial support structure of any one of the preceding claims, 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 the preceding claims, wherein the artificial support structure has a suture retention strength of about 22.03N to about 24.27N.

33. The artificial support structure of any one of the preceding claims, wherein the artificial support structure has a burst strength of about 140N to about 170N.

34. The artificial support structure of any one of the preceding claims, wherein the artificial support structure has a burst strength of about 145N to about 163N.

35. The artificial support structure of any one of the preceding claims, wherein the artificial support structure has a burst strength of about 147.14N to about 161.26N.

36. The artificial support structure of any one of the preceding claims, wherein the artificial support structure has a tear resistance of about 18N to about 26N.

37. The artificial support structure of any one of the preceding claims, wherein the artificial support structure has a tear resistance of about 19N to about 25N.

38. The artificial support structure of any one of the preceding claims, wherein the artificial support structure has a tear resistance of about 19.87N to about 24.92N.

39. An artificial support structure, comprising one or more biodegradable polymers and one or more extracellular matrix materials, the support structure further comprising: a plurality of unit patterns, each unit pattern comprising a plurality of filaments repeatedly arranged to form columns or rows symmetrical to each other, each unit pattern being constituted by sides of a closed shape to thereby form a hole therein, The column or row along which the plurality of unit patterns are repeatedly arranged has an Euler locus.

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

41. The artificial support structure according to any one of claims 39 or 40, wherein at least one unit pattern has a diameter between about 200 microns and about 3.5 mm.

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

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

44. The artificial support structure according to any one of claims 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 claims 39 to 44, wherein the one or more extracellular matrix materials is collagen I.

46. ​​An artificial support structure according to any one of claims 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 claims 39 to 46, wherein the plurality of connected unit patterns form a three-dimensional macrostructure.

48. The artificial support structure of any one of claims 39 to 47, wherein the artificial support structure has a thickness between about 0.5 mm and about 1.5 mm.

49. The artificial support structure of any one of claims 39 to 48, wherein the artificial support structure has a thickness between about 0.7 mm and about 1.3 mm.

50. The artificial support structure of any one of claims 39 to 40, wherein the artificial support structure has a thickness between about 0.9 mm and about 1.1 mm.

51. The artificial support structure according to any one of claims 39 to 50, wherein the artificial support structure contains 1 to 5 layers.

52. The artificial support structure of claim 51, wherein the layer further has a thickness between about 0.10 mm and about 0.3 mm.

53. The artificial support structure according to any one of claims 51 or 52, wherein the layer further has a thickness between 0.15 mm and about 0.25 mm.

54. The artificial support structure according to any one of claims 51 to 53, wherein the layer further has a thickness between 0.18 mm and about 0.22 mm.

55. An artificial support structure according to any one of claims 39 to 54, wherein one or more of the plurality of filaments has a diameter of less than 550 mm.

56. An artificial support structure according to any one of claims 39 to 55, wherein one or more of the plurality of filaments has a diameter of less than 500 mm.

57. An artificial support structure according to any one of claims 39 to 56, wherein one or more of the plurality of filaments has a diameter of less than 400 mm.

58. The artificial support according to any one of claims 39 to 57, wherein the columns or rows along which the plurality of unit patterns are repeatedly arranged are connected to allow the plurality of unit patterns to have intersections with the plurality of unit patterns of adjacent columns or rows.

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

60. The artificial support according to claim 59, wherein four adjacent unit patterns are connected to have four intersections with each other and have four sides 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 according to any one of claims 39 to 60, wherein each unit pattern is a capital "I" of the English alphabet.

62. An artificial support according to claim 61, wherein the short sides of the sides of the closed shape of each unit pattern have the same length as each other, and the long sides thereof have the same length as each other, so that the space surrounded by the four unit patterns has the same shape as each unit pattern.

63. The artificial support according to claim 62, wherein: In the closed shape, the length ratio of the short side to the long side is 1:

3.

64. The artificial support according to claim 63, wherein: In the closed shape, a length ratio of each short side to each long side is 1:

3. 65 . The artificial support according to claim 64 , wherein the plurality of unit patterns in a column or a row along which the plurality of unit patterns are repeatedly arranged have an angle of 45° or 135° with respect to the row or the column.

66. The artificial support according to claim 65, wherein portions of sides of the plurality of unit patterns are regularly arranged to form sides of the artificial support.

67. An artificial support structure according to any one of claims 39 to 66, wherein the artificial support has an ultimate tensile strength between about 4.05 MPa and about 4.7 MPa.

68. An artificial support structure according to any one of claims 39 to 67, wherein the artificial support has an ultimate tensile strength between about 4.12 MPa and about 4.50 MPa.

69. The artificial support structure of any one of claims 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 claims 39 to 69, wherein the artificial support structure has an elastic modulus of about 3.00 MPa to about 4.10 MPa.

71. The artificial support structure of any one of claims 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 claims 39 to 71, wherein the artificial support structure has a suture retention strength of about 20N to about 26N.

73. The artificial support structure of any one of claims 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 claims 39 to 73, wherein the artificial support structure has a suture retention strength of about 22.03N to about 24.27N.

75. The artificial support structure of any one of claims 39 to 74, wherein the artificial support structure has a burst strength of about 140N to about 170N.

76. The artificial support structure of any one of claims 39 to 75, wherein the artificial support structure has a burst strength of about 145N to about 163N.

77. The artificial support structure of any one of claims 39 to 76, wherein the artificial support structure has a burst strength of about 147.14N to about 161.26N.

78. The artificial support structure of any one of claims 39 to 77, wherein the artificial support structure has a tear resistance of about 18N to about 26N.

79. The artificial support structure of any one of claims 39 to 78, wherein the artificial support structure has a tear resistance of about 19N to about 25N.

80. The artificial support structure of any one of claims 39 to 79, wherein the artificial support structure has a tear resistance of about 19.87N to about 24.92N.

81. A scaffold comprising a patterned polymer substrate having a coating of one or more extracellular matrix (ECM) materials thereon, wherein the pattern of the polymer substrate comprises a series of adjacent rows of unit cell structures, each unit cell structure being generally in the shape of the letter "I", the unit cell structures being arranged in the rows of the patterned polymer substrate in a vertical alternating pattern of the unit cell structures.

82. A support according to claim 81, wherein the unit cell structures in the series are further defined as comprising holes formed as center lines, the length of the center lines being greater than the length of two lines of substantially equal length each perpendicular to opposite ends of the center lines, and wherein the alternating pattern is configured so that each of the ends of the center lines of the holes are generally perpendicular to the center lines of the holes of adjacent unit cell structures.

83. A support according to claim 81 or 82, wherein the support is configured as one or more sheets, each sheet comprising a first planar side and a second planar side.

84. A support according to claim 83, wherein the support comprises 1, 2, 3, 4 or 5 sheets, or comprises at least or no more than 1, 2, 3, 4 or 5 sheets.

85. A bracket according to claim 83 or 84, wherein the plurality of sheets are arranged so that a planar side of one sheet is adjacent to a planar side of another sheet.

86. A stent according to any one of claims 82 to 85, wherein the stent comprises one or more defined shapes.

87. A stent according to claim 86, wherein the defined shape is generally a line, a curve, a circle, a square, a crescent, a triangle, a rectangle, an ellipse, a trapezoid, or wherein the stent includes markings for one or more of the defined shapes.

88. The stent of any one of claims 81 to 87, wherein the polymer matrix comprises polycaprolactone, polydioxanone, or a combination thereof.

89. The stent of any one of claims 81 to 88, wherein the polymer matrix consists of polycaprolactone.

90. The scaffold of any one of claims 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.

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

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

94. The stent of any one of claims 81 to 93, wherein the coating is contained on a first side of the sheet, a second side of the sheet, or both the first side and the second side of the sheet.

95. The stent of any one of claims 81 to 94, wherein the coating fills the pores of a plurality of unit cell structures of the stent.

96. The stent of any one of claims 81 to 95, wherein the coating fills a majority of the pores of the unit cell structure of the stent.

97. The stent of any one of claims 81 to 96, wherein the coating fills the pores of substantially all of the unit cell structures of the stent.

98. The stent of any one of claims 81 to 97, wherein the coating does not fill the pores of a majority of the unit cell structure of the stent.

99. The stent of any one of claims 81 to 98, wherein the coating does not fill the pores of substantially all unit cell structures of the stent.

100. The stent of any one of claims 81 to 99, wherein the stent has a thickness no greater than 1 mm.

101. The stent of any one of claims 81 to 100, wherein the stent further comprises one or more therapeutic agents.

102. The stent 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. A method of producing a stent according to any one of claims 81 to 102, the 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 crosslinking agents; (d) optionally washing the substrate; as well as (e) subjecting the substrate to conditions at a temperature below 15°C, optionally wherein the one or more ECM materials and the one or more cross-linking agents are mixed together prior to application to the substrate.

104. The method of claim 103, wherein the polymer substrate consists 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.

106. The method of any one of claims 103 to 105, wherein the applying comprises placing the substrate on top of a solution of the coating.

107. The method of any one of claims 103 to 106, wherein the applying comprises spraying, dripping or placing the coating on the substrate.

108. The method of any one of claims 107 to 111, wherein the applying is performed for 1 hour to 24 hours, 5 hours to 24 hours, 5 hours to 20 hours, 8 hours to 20 hours, 8 hours to 15 hours, or 9 hours to 11 hours.

109. The method of any one of claims 103 to 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.

110. The method of any one of claims 103 to 109, wherein (c) is performed for about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours.

111. The method according to any one of claims 103 to 110, wherein the washing is carried out with water.

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

113. The method of any one of claims 103 to 112, wherein (e) is performed for about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours.

114. The method according to any one of claims 103 to 113, wherein after (e), the produced scaffold is subjected to drying.

115. The method of any one of claims 103 to 114, further comprising applying one or more therapeutic agents to the stent.

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 outside of the stent.

117. The method of any one of claims 103 to 116, wherein the degradation of the patterned polymer substrate can be regulated based on the concentration of the crosslinking agent.

118. The method of any one of claims 103 to 117, comprising washing the substrate after subjecting the substrate to one or more cross-linking agents.

119. A method according to any one of claims 103 to 117, wherein the stent is produced into a defined shape.

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

121. A method of enhancing soft tissue in an individual in need thereof, the method comprising applying an effective amount of a scaffold according to any one of claims 1 to 102 to one or more soft tissue sites of the individual.

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

124. The method of any one of claims 121 to 123, wherein the soft tissue is 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 claims 121 to 124, wherein the soft tissue comprises breast tissue for breast reconstruction, breast reduction, or breast augmentation.

126. The method of any one of claims 121 to 125, wherein the soft tissue comprises a hernia.

127. The method of any one of claims 121 to 126, wherein the applying comprises securing the stent to the soft tissue of the individual and / or tissue of the individual adjacent to the soft tissue.

128. The method of claim 127, wherein the fixing is further defined as suturing, stapling, or using surgical glue to fix the support to the soft tissue of the individual and / or tissue of the individual adjacent to the soft tissue.

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

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

131. The method of claim 129 or 130, wherein the suture of the suturing 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 arranged in a series of adjacent rows of vertically alternating unit cell structures, each unit cell structure generally comprising a hole shaped to have a center line, the length of the center line being greater than the length of two lines of substantially equal length each perpendicular to opposite ends of the center line, wherein the alternating pattern is configured so that each of the ends of the center line of the hole is generally perpendicular to the center line of the hole of an adjacent unit cell structure.

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

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

135. The pliable sheet of claim 134, further defined as a unit cell structure comprising a coating of one or more ECM materials.

136. The flexible sheet of any one of claims 132 to 135, wherein the pores are filled with the coating.

137. The flexible sheet of any one of claims 132 to 136, wherein the one or more ECM materials comprise type I collagen.

138. A flexible sheet material according to any one of claims 132 to 137, contained in suitable packaging.

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