3-Dimensional Biocompatible Structure for Tissue Repair

Abstract

The present invention provides a biocompatible three-dimensional scaffold and a composition for reconstructing cavitized tissue containing the same. The present invention provides mechanical support for a depressed space by possessing robust physical strength, while also being able to fill the internal space with an effective component for tissue regeneration, thereby efficiently inducing the quantitative recovery of irreversibly lost tissue. Furthermore, by using a spherical scaffold, the present invention can be efficiently inserted into a depressed area of ​​any shape and can be usefully utilized as a human implantable scaffold for restoring various fatty tissues, including breast tissue, by degrading at an appropriate time after regeneration is complete.

Description

Technology Field

[0001] The present invention relates to a biocompatible scaffold having a spherical or near-spherical geometric structure and a method for repairing breast tissue cavitized by surgical partial resection or the like using the same. Background Technology

[0003] Breast cancer refers to a malignant tumor that originates from breast cells. Although the exact cause of breast cancer has not been clearly identified, various factors such as female hormones, family history, medical history, childbirth history, and dietary habits are being cited. It is known that the 5-year survival rate for stage 4 breast cancer is less than 20%, compared to 100% for stage 0 cancer. Recently, the incidence of breast cancer has been rapidly increasing among women undergoing periods of vigorous physiological changes—such as low birth rates, short breastfeeding periods, early menarche, and late menopause—due to increased sensitivity of mammary gland tissue resulting from a rapid increase in the frequency of stimulation by female hormones, as well as the Westernization of dietary habits and environmental pollution. Given the current state of Westernization, this increase in the incidence and mortality rates of breast cancer is expected to continue for a considerable period.

[0004] As of 2020, more than 2 million people in Korea are newly diagnosed with breast cancer annually, and the prevalence rate is increasing by 5% each year. Regarding surgical procedures for early-stage breast cancer, lumpectomy has been gradually increasing, reaching twice the rate of total mastectomy as of 2018. For reconstruction following lumpectomy, methods primarily used include reconstructing the opposite breast, inserting implants into the excised breast, or transplanting autologous fat harvested from the abdomen. Contralateral breast reconstruction is not only expensive but also has the disadvantage of creating new scars in non-lesion areas, despite being a cosmetic procedure unrelated to survival. When implants are inserted for aesthetic correction, the use of expensive cadaver-derived dermis leads to high costs and unsatisfactory reconstructive results. Meanwhile, autologous fat transplantation carries the risk of skin-soft tissue fibrosis and adhesions caused by radiation therapy, and presents difficulties as the fat tissue is absorbed over time, causing the reconstructive effect to disappear. Accordingly, there is a need for the development of new therapeutic approaches to efficiently and safely reconstruct lost tissue.

[0006] Throughout this specification, numerous papers and patent documents are referenced and cited. The disclosures of the cited papers and patent documents are incorporated by reference into this specification in their entirety to more clearly explain the state of the art to which the present invention pertains and the content of the present invention. Prior art literature

[0008] Patent Document 1. Patent Publication No. 10-2022-0079816 The problem to be solved

[0009] The inventors have made diligent research efforts to develop a three-dimensional structure for tissue regeneration that efficiently restores tissue cavities caused by trauma or surgical excision. As a result, they discovered that when a spherical or hemispherical, specifically a spherical porous structure (scaffold) made of a biocompatible polymer and hollow inside is inserted into a depressed tissue cavity, it possesses robust physical strength to provide mechanical support for the depressed space, while also enabling the loading of effective components that aid tissue regeneration into the internal space, thereby inducing quantitative recovery of lost tissue. Furthermore, by degrading at an appropriate time after insertion, it can be usefully utilized as a structure for human implantation for the restoration of breast tissue, etc., thereby completing the present invention.

[0010] Therefore, the objective of the present invention is to provide a three-dimensional structure for tissue regeneration.

[0011] Another objective of the present invention is to provide a composition for reconstructing cavitation tissue.

[0013] Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims, and drawings. means of solving the problem

[0015] According to one aspect of the present invention, the present invention provides a three-dimensional structure (scaffold) for tissue regeneration comprising the following:

[0016] (a) one or more spherical or hemispherical porous layers made of biocompatible polymers; and

[0017] (b) A cavity formed inside the porous surface layer.

[0018] The inventors have made diligent research efforts to develop a three-dimensional structure for tissue regeneration that aims for the efficient regeneration of irreversibly lost tissue and, in particular, restores tissue cavities caused by trauma or surgical excision. As a result, it was discovered that when a spherical or hemispherical, specifically a spherical porous structure made of a biocompatible polymer and hollow inside is inserted into a depressed tissue cavity, it possesses robust physical strength to provide mechanical support for the depressed space, while also enabling the loading of active ingredients that aid tissue regeneration into the internal cavity. This not only induces the quantitative recovery of lost tissue but also degrades at an appropriate time after insertion, making it useful as a structure for human implantation to restore various tissues, including breast tissue.

[0019] In this specification, the terms “structure” or “scaffold” refer to a tissue engineering structure designed to promote the recovery and regeneration of damaged tissue by encapsulating living cells, specifically cells derived from damaged tissue or cells involved in the recovery of damaged tissue. Specifically, the structure of the present invention may be a single-layer structure composed of a single porous sphere, or a multi-layer structure in the form of a core-shell in which a plurality of spheres are stacked.

[0020] In this specification, the term “spherical” refers to a three-dimensional shape composed of a set of points that are equidistant from the center, but the “spherical” surface layer of the present invention does not need to be geometrically perfect spheres and includes all structures in which the distance from each point on the strand constituting the surface layer to the center does not exceed a certain range.

[0021] According to a specific embodiment of the present invention, the spherical or hemispherical porous surface layer of the present invention has a geometry selected from the group consisting of an icosahedron, a truncated icosahedron, and a truncated octahedron.

[0022] According to another embodiment of the present invention, the spherical or hemispherical porous surface layer of the present invention may have a spherical or near-spherical shape formed by three-dimensionally molding a planar radial structure, in which case it has a curved surface rather than a polyhedron.

[0023] Most specifically, the spherical or hemispherical porous surface layer of the present invention has the geometry of a truncated icosahedron. In this specification, the term “truncated icosahedron” refers to a soccer ball-shaped polyhedron formed by cutting off each vertex (the trisection point of the edge) of an icosahedron in which each face is made of an equilateral triangle.

[0024] By using a scaffold with a spherical or near-spherical geometry in this way, it can be efficiently inserted into every corner of the sunken space regardless of the shape of the cavity area, and can be standardized and produced regardless of the shape or volume of the cavity area to be restored.

[0025] According to a specific embodiment of the present invention, the porous surface layer may be formed by crossing biocompatible polymer strands, and two or more types of biocompatible polymers may be mixed and used.

[0026] According to the present invention, the surface of the porous sphere (or hemisphere) of the present invention can be formed by strands having a constant thickness intersecting at regular intervals to form pores of a constant size.

[0027] According to a specific embodiment of the present invention, the strand has a diameter of 0.1 to 50 mm. If the diameter is smaller than 0.1 mm, it is difficult to maintain the shape of the three-dimensional structure after insertion into the human body, which reduces its role as a support; if the diameter is larger than 50 mm, tissue regeneration is difficult, biodegradation takes a long time, and elasticity is reduced. More specifically, the strand has a diameter of 0.5 to 30 mm, even more specifically, a diameter of 0.7 to 20 mm, even more specifically, a diameter of 0.8 to 1.5 mm, and most specifically, a diameter of about 1 mm.

[0028] In this specification, the term “polymer” refers to a synthetic or natural polymer compound in which monomers of the same or different types are sequentially combined. Accordingly, polymers include homopolymers (polymers in which one type of monomer is polymerized) and copolymers prepared by the polymerization of at least two different monomers, and copolymers include copolymers (polymers prepared from two different monomers) and polymers prepared from more than two different monomers.

[0029] In this specification, the term “biocompatibility” refers to a property that does not cause short-term or long-term side effects when administered into the body and comes into contact with the cells, tissues, or body fluids of an organ. Specifically, it includes tissue compatibility and blood compatibility, which do not cause tissue necrosis or blood coagulation upon contact with biological tissue or blood, as well as biodegradability, which disappears after a certain period following administration into the body.

[0030] In this specification, the term “biodegradable” means the property of naturally degrading when exposed to a physiological solution of pH 6-8, and specifically means the property of being able to degrade over time by body fluids, degrading enzymes, or microorganisms in the body.

[0031] 본 발명에서 사용 가능한 생체적합성 고분자는 PCL[poly(caprolactone)], HEMA[poly(2-hydroxyethyl metacrylate)], PVA(polyvinylalcohol, PEO(Polyethyleneoxide), phospholipid, collagen, alipatic polyether, PLA[poly(lactide)], PGA[poly(glycolide)], PDO[poly(dioxanone)]), PBL[poly(butyrolactone)], PVL[poly(valerolactone)], PLGA[poly(lactide-co-glycolide)], PU(polyurethane), fibronectin, vitronectin, poly(L-lysin), poly(L-glutamic acid), Poly(aspartic acid), carboxymethyl cellulose, cellulose sulfate, agarose, alginate, carrangeenan, hyaluronic acid, dextran, chitosan, poly(hydroxybutyric acid), poly(alkylene succinate), polyamide, poly(anhydride), poly(ortho-ester), poly(cyano acrylates), polyphosphazene, poly(hydroxyethyl metacrylate), poly(methyl metacrylate), poly(tetrafluoroethylene), poly(dimethylsiloxane), poly(ethyleneoxide-β-propyleneoxide), Poly(vinylmethylether), Poly(N-alkylacrylamide), decelluarized matrix (dECM) 및 이들의 조합을 포함하나, 이에 제한되는 것은 아니다.More specifically, the biocompatible polymer used in the present invention is an aliphatic polyester, PLA [poly(lactide)], PGA [poly(glycolide)], PDO [poly(dioxanone)]), PBL [poly(butyrolactone)], PVL [poly(valerolactone)], PLGA [poly(lactide-co-glycolide)], PCL [poly(caprolactone)], or a combination thereof, most specifically PCL [poly(caprolactone)].

[0033] The biocompatible three-dimensional structure of the present invention can be coated with collagen on a biocompatible polymer strand.

[0034] In this specification, the term “coating” refers to forming a new layer of a certain thickness by modifying a specific material on a target surface, and the target surface and the coating material may be modified through ionic bonding or non-covalent bonding. The term “non-covalent bonding” is a concept that includes not only physical bonding such as adsorption, cohesion, entanglement, and entrapment, but also bonding that occurs when interactions such as hydrogen bonding and van der Waals bonding act alone or in combination with said physical bonding. In the present invention, when a collagen solution coats the strands constituting the scaffold, it may form a sealed layer that completely surrounds the surface of each strand or may form a partially sealed layer.

[0035] According to a specific embodiment of the present invention, the structure has a diameter of 3 to 200 mm. If the diameter is smaller than 3 mm, significant adipose tissue regeneration is not smooth, and if the diameter is 200 mm or more, it is difficult to insert into the tissue depression.

[0036] More specifically, the above structure (scaffold) has a diameter of 10 to 100 mm, more specifically, a diameter of 15 to 50 mm, more specifically, a diameter of 20 to 40 mm, and most specifically, a diameter of about 30 mm.

[0038] According to another aspect of the present invention, the present invention provides a composition for cavitation tissue reconstruction comprising the scaffold of the present invention described above; and collagen, adipose tissue, mammary gland tissue, or a combination thereof as an active ingredient.

[0039] As described above, the scaffold of the present invention can be loaded with active ingredients that aid in tissue regeneration, including collagen, adipose tissue, and mammary gland tissue, within its internal empty space. These active ingredients for tissue regeneration may be appropriately selected to include not only collagen, adipose tissue, and mammary gland tissue, but also cells or tissue masses derived from the tissue to be regenerated, depending on the nature of the tissue to be regenerated. Furthermore, the active ingredients that aid in tissue regeneration may be implanted into the lesion site while filled with the internal space of the scaffold of the present invention, or the scaffold may be implanted into the lesion site first and then filled with the internal space of the scaffold prior to suturing.

[0040] In this specification, the term "transplantation" refers to the process of delivering viable tissue, cells, active ingredients that aid in tissue regeneration, or artificial scaffolds containing these from a donor to a recipient for the purpose of maintaining the functional integrity of the tissue or cells transplanted to the recipient. Accordingly, the term "transplantation scaffold" refers to a physical support used in the process of delivering viable tissue or cells to a recipient.

[0041] According to a specific embodiment of the present invention, the cavitation tissue is adipose tissue or fibrous tissue, and more specifically, the adipose tissue is breast adipose tissue.

[0043] According to another aspect of the present invention, the present invention provides a radial porous mesh made of a biocompatible polymer for forming a three-dimensional scaffold for tissue regeneration according to the present invention. The porous mesh of the present invention can form a “spherical porous surface layer having a cavity” according to the present invention by forming a spindle shape in the shape of spokes with a plurality of straight meshes extending from the center, and molding them into a sphere shape so that their corresponding ends meet.

[0044] According to a specific embodiment of the present invention, the porous mesh may include a fixing part and a fixing part receiving part at each of the two opposing ends with respect to the radial center. In this way, by mechanically joining the two corresponding ends of the straight mesh extending from the center in a spoke-like shape through the fixing part and the fixing part receiving part, the spherical porous surface layer can be made more robust. Such fixing part and the fixing part receiving part may be formed at only one pair of corresponding ends (left side of FIG. 2c), at multiple pairs of corresponding ends, or at all pairs of corresponding ends (right side of FIG. 2c).

[0045] In addition, when a fixed part is formed at one end, a receiving part of the fixed part is formed at all other ends as well as the corresponding end, so that one fixed part and multiple receiving parts of the fixed part can be combined (left side of FIG. 2c).

[0046] According to another specific embodiment, the porous mesh has eight ends extending from the center of the radial, seven of which include a fixing part or a fixing part receiving part, and one end may include seven fixing part receiving parts or fixing parts capable of forming a combination with the fixing part or fixing part receiving part included in the remaining seven ends (middle of FIG. 2c).

[0047] The fixed part and the fixed part receiving part may, for example, be a hook and a hook receiving part, respectively, but are not limited thereto, and any fastening means capable of forming a mechanical connection and fixing the formed connection may be applied.

[0048] According to another aspect of the present invention, the present invention provides a method for reconstructing cavitation tissue of a subject, comprising the step of implanting collagen, adipose tissue, mammary gland tissue, or a combination thereof into the cavitation tissue of the subject.

[0049] As the scaffold, collagen, adipose tissue, and mammary gland tissue used in the present invention have already been described above, their description is omitted to avoid excessive duplication. Effects of the invention

[0051] The features and advantages of the present invention are summarized as follows:

[0052] (a) The present invention provides a biocompatible three-dimensional scaffold and a composition for reconstructing cavitized tissue comprising the same.

[0053] (b) The present invention provides mechanical support for the depressed space by having robust physical strength, while also being able to fill the internal space with an active ingredient for tissue regeneration, thereby efficiently inducing the quantitative recovery of irreversibly lost tissue.

[0054] (c) The present invention can also be usefully utilized as a human implantable scaffold for restoring various fatty tissues, including breast tissue, by using a spherical scaffold, which is efficiently inserted into a depression of any shape and decomposes at an appropriate time after regeneration is complete. Brief explanation of the drawing

[0056] FIG. 1 is a schematic diagram showing the process of partially restoring lost breast tissue by applying the biocompatible three-dimensional structure of the present invention, and the sunken breast can be restored by inserting the structure of the present invention into a cavity that occurs after partial mastectomy. FIG. 2 is a structural diagram of the biocompatible three-dimensional structure of the present invention having various strand shapes, respectively, illustrating a sphere (Fig. 2a), a hemisphere (Fig. 2b), and a radial structure for forming a spherical structure (Fig. 2c). Figure 3 shows microCT images of the transverse section (Fig. 3a) and longitudinal section (Fig. 3b) of the transplanted site after 2, 4, and 6 months, respectively, following the transplantation of the biocompatible 3D scaffold of the present invention into a rat model, and the results of H&E staining and Masson's trichrome staining performed after transversely sectioning the tissue of the transplanted site. Figure 4 shows the results of performing H&E staining and Masson's trichome staining on tissue sections of the transplanted site after 3 months had passed since the biocompatible 3D scaffold of the present invention was transplanted into a pig model. Specific details for implementing the invention

[0057] The present invention will be described in more detail below through examples. These examples are intended solely to explain the invention more specifically, and it will be obvious to those skilled in the art that the scope of the invention is not limited by these examples according to the gist of the invention.

[0059] Examples

[0060] Preparation Example 1: Preparation of a biocompatible three-dimensional structure

[0061] A 3D printer (RAISE 3D, USA) was used to manufacture a three-dimensional polymer structure, and the 3D printing technique allows for easy adjustment of the size of the three-dimensional structure according to conditions such as nozzle diameter, temperature, extrusion pressure, and nozzle travel speed. To occupy the volume of the lost portion within the tissue while possessing high mechanical elasticity, the inventors fabricated a three-dimensional structure having an overall sphere shape by geometrically intersecting strands with a diameter of 1 mm. Polycaprolactone (PCL, Polycaprolactone, Sigma-Aldrich, USA) was used as the raw polymer, and for the fabrication of the polymer mesh, the nozzle diameter was set to 0.4 mm, the nozzle temperature to 130°C, the printing speed to 5 mm / s, and the nozzle travel speed to 40 mm / s. With the settings completed, a three-dimensional structure having a truncated icosahedral structure with a diameter of 1 cm and a strand thickness of 1 mm was fabricated. Subsequently, sterilization was performed using an e-beam before use in the experiment. The fabricated three-dimensional polymer structure forms a hollow spherical structure with a mesh of various shapes formed on the surface as each strand intersects in various forms (Fig. 2).

[0063] Preparation Example 2: Fabrication of collagen-coated biocompatible 3D structures

[0064] Collagen coating using a collagen solution was additionally performed on the biocompatible three-dimensional structure prepared in Preparation Example 1. A collagen solution was prepared by dissolving atelocollagen extracted from porcine dermis (Type 1, medical device grade, Darim Tissen, Korea) at a concentration of 0.5% in 0.5M acetic acid at 4°C for 12 hours.

[0065] To achieve a uniform coating of collagen, hydrophilicity was imparted to highly hydrophobic polycaprolactone by performing a plasma surface treatment. A polycaprolactone 3D structure was placed on a glass Petri dish and treated using a plasma surface treatment device (PDC-32G-2 Plasma, Harrick Plasma, USA) for 60 seconds under medium vacuum conditions of 1.0-0.1 Torr.

[0066] After the surface treatment process, the sample was placed on a plate of a certain height, and a collagen solution was added to sufficiently submerge the 3D structure, followed by a coating process at 4°C for 30 minutes. After the coating process was completed, the sample was cooled to -50°C for 3 hours, and then dried using a freeze dryer (MG-VFD5, MG Indus., KOREA) for 14 hours to create a porous surface structure of the coated collagen.

[0067] Subsequently, a neutralization process was performed to remove acetic acid present in the form of salts within the freeze-dried collagen. To this end, the freeze-dried specimens were washed four times for 15 minutes each using anhydrous alcohol (Ethanol absolute, Merck KGaA, Germany), followed by neutralization of the acetic acid four times for 15 minutes each using 0.5 M NaOH (Duksan General Science, Korea) dissolved in 70% ethanol. Afterward, to remove any remaining NaOH, the specimens were washed sequentially four times for 15 minutes each using 50% and 30% ethanol and triple-distilled water. The washed collagen-coated 3D structures were cooled to -50°C for 3 hours, and then dried using a freeze-dryer for 12 hours as previously mentioned. Finally, sterilization was performed using an e-beam prior to use in the experiment.

[0068] The fabricated three-dimensional polymer structure forms a hollow spherical structure with a mesh of various shapes formed on the surface by each strand intersecting in various forms.

[0070] Experimental Example 1: Rat model animal experiment

[0071] The inventors intended to evaluate whether the introduction of the three-dimensional polymer structure of the present invention could be applied to tissue regeneration, for example, partial breast reconstruction. The experiment was conducted by dividing the subjects into a total of four groups: a group in which approximately 50% of the mammary gland tissue of SD rats (8 weeks old, female) was excised with surgical scissors and sutured; a group in which approximately 50% of the mammary gland tissue was excised with surgical scissors, the three-dimensional structure (PCL ball) of Preparation Example 1 was implanted into the excised mammary gland tissue area, and sutured; a group in which approximately 50% of the mammary gland tissue was excised with surgical scissors, the three-dimensional structure (PCL-col ball) of Preparation Example 2 was implanted, a collagen preparation was injected into the three-dimensional structure, and sutured; and a group in which approximately 50% of the mammary gland tissue was excised with surgical scissors, the three-dimensional structure of Preparation Example 2 was implanted, mouse mammary gland tissue was inserted into the three-dimensional structure, and sutured.

[0072] At 2, 4, and 6 months after suturing, the transplant site was imaged using microCT (Quantum GX2 microCT Imaging System, PerkinElmer), and each experimental animal was sacrificed to extract tissue from the area where the 3D structure was transplanted. The tissue was then sectioned vertically or horizontally, followed by H&E (hematoxylin & eosin) staining and Masson's trichrome staining. As a result, as shown in Figures 3a and 3b, microCT scans at 2, 4, and 6 months of mice that had about 50% of their mammary gland tissue resected and received no treatment showed no recovery of the lost tissue. In contrast, microCT scans at 2, 4, and 6 months of mice that had the 3D structure of the present invention transplanted showed that tissue was significantly formed within the 3D structure over time. In the group in which collagen was injected into the 3D structure after implantation, it was confirmed that tissue detected as opaque on microCT within the 3D structure was continuously maintained. In the group in which mouse mammary gland tissue was filled into the structure and sutured after implantation, it was observed that tissue gradually grew within the structure over time. Through H&E staining, it was confirmed that tissue was generated within the internal cavity in all cases: when only the 3D structure was implanted, when the 3D structure injected with collagen was implanted, and when the 3D structure inserted with mammary gland tissue was implanted. In particular, in the group implanted with the 3D structure, adipose tissue was observed to have formed and entered from the periphery into the structure, while in the 3D structure injected with collagen, regeneration into fibrous tissue was confirmed. Furthermore, in the 3D structure inserted with mammary gland tissue, it was observed that the mammary gland tissue was well maintained within the structure and regenerated in a form where fibrous tissue surrounded the mammary gland tissue.

[0073] In addition, through Masson's trichrome staining, it was observed that a large amount of collagen was produced inside the 3D structure injected with collagen preparations compared to the 3D structure. Considering that injected collagen typically degrades within 1-2 months, it was confirmed that fibrous tissue was formed by the injected collagen, and by the 6th month, the tissue was composed and restored using collagen secreted from the fibrous tissue. Furthermore, it was found that inside the 3D structure into which mammary gland tissue was inserted, the remaining tissues, excluding the mammary gland tissue, were fibrous tissues composed of collagen.

[0075] Experimental Example 2: Pig Model Animal Experiment

[0076] To construct a minipig partial mastectomy model, 12-month-old adult minipigs were reared in an SPF facility. After providing a one-week acclimatization period, anesthesia was induced by intramuscular injection of 1 mg / kg alfaxane and 2 mg / kg xylazine, and the anesthetic state was maintained by inhaling 2% isoflurane during surgery. After sterilizing the surgical site of the minipig with 70% ethanol and iodine, 15 ml of mammary gland tissue was partially resected to construct the partial mastectomy model. Three-dimensional structures of Preparation Example 1 (PCL ball) and Preparation Example 2 (PCL-col ball) were implanted into the partially resected surgical site, and the area was sutured. Subsequently, 20 mg / kg cefazolin and 0.4 mg / kg meloxicam were intramuscularly injected for three days. Three months after surgery, the minipigs were sacrificed by injecting KCL under general anesthesia, and the transplanted PCL balls and PCL-col balls were retrieved. Subsequently, the cells and tissues were fixed by washing them three times with PBS (Phosphate-buffered saline) and treating them with a 10% formalin solution. To confirm the characteristics of the fixed tissues, H&E (Hematoxylin & Eosin) staining and Masson's trichrom staining were performed. As a result, as shown in Figure 4, it was confirmed that tissue originating from within the minipigs had entered and formed inside the PCL balls and PCL-col balls three months after transplantation into the partial mastectomy model. Furthermore, in the group transplanted with PCL balls, a small amount of fibrous tissue was formed inside the PCL balls and autologous mammary gland tissue was introduced from the outside, whereas in the group transplanted with PCL-col, a large amount of fibrous tissue was formed inside the PCL-col balls and almost no autologous mammary gland tissue was introduced from the outside.

[0078] Foregoing, specific parts of the present invention have been described in detail. It is evident to those skilled in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of the invention. Accordingly, the actual scope of the invention is defined by the appended claims and their equivalents.

Claims

Claim 1 A three-dimensional scaffold for tissue regeneration formed by molding a radial planar porous mesh made of a biocompatible polymer selected from the group consisting of PCL [poly(caprolactone)], aliphatic polyester, PLA [poly(lactide)], PGA [poly(glycolide)], PDO [poly(dioxanone)]), PBL [poly(butyrolactone)], PVL [poly(valerolactone)], PLGA [poly(lactide-co-glycolide)], polyL-lysine, polyL-glutamic acid, polyaspartic acid, poly(hydroxybutyric acid), poly(alkylene succinic acid), polyanhydride, poly(ortho ester), polycyanoacrylate, and combinations thereof, wherein the porous mesh comprises a plurality of straight meshes extending radially from the center of the radial shape, and the ends of the straight meshes comprise a fixation portion or a fixation portion receiving portion, and among the ends, the fixation portion A three-dimensional scaffold for tissue regeneration characterized by having at least one pair of end portions including a portion Claim 2 A scaffold according to claim 1, characterized in that the porous surface layer is formed by intersecting biocompatible polymer strands. Claim 3 delete Claim 4 delete Claim 5 A scaffold according to claim 2, characterized in that the strand has a diameter of 0.1 to 50 mm. Claim 6 A scaffold according to claim 5, characterized in that the strand is coated with collagen. Claim 7 A scaffold according to claim 1, characterized in that the scaffold has a diameter of 3 to 200 mm. Claim 8 delete Claim 9 delete Claim 10 A scaffold according to any one of claims 1, 2 and 5 to 7; and a composition for cavitation tissue reconstruction comprising collagen, adipose tissue, mammary gland tissue, or a combination thereof as an active ingredient. Claim 11 A composition for reconstructing cavitized tissue according to claim 10, characterized in that the cavitized tissue is adipose tissue or fibrous tissue. Claim 12 A composition for reconstructing cavitation tissue, characterized in that, in claim 11, the adipose tissue is breast adipose tissue. Claim 13 delete Claim 14 delete Claim 15 delete

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