Biocompatible three-dimensional structures for tissue repair

Abstract

The present invention provides a biocompatible three-dimensional scaffold and a composition for reconstructing hollow tissue comprising the same. The present invention has strong physical strength and provides mechanical support for the recessed space, while allowing the internal space to be filled with an active ingredient for tissue regeneration, and efficiently induces the quantitative recovery of irreversibly lost tissue. The present invention also uses a spherical scaffold that can be efficiently inserted into recessed sites of any shape, and is degraded at an appropriate time after regeneration is completed, making it useful as a human implant scaffold for repairing various adipose tissues, including breast tissue.

Description

[Technical field]

[0001] The present invention relates to a biocompatible scaffold having a spherical or near-spherical geometry and a method of using the same to restore breast tissue hollowed out by, for example, a surgical partial resection. [Background technology]

[0002] Breast cancer is a malignant tumor that develops in the cells of the breast. Although the causes of breast cancer have not been clearly identified, various factors such as female hormones, family history, past history, reproductive history, and dietary habits have been identified. The five-year survival rate for breast cancer is less than 20% for stage 4 cancer, compared to 100% for stage 0 cancer. In women who are going through physiologically active physical changes such as low birth rates, short lactation periods, early menarche, and late menopause, the incidence of breast cancer has recently increased rapidly due to the increased sensitivity of breast tissue due to the sudden increase in the number of times they are stimulated by female hormones, the westernization of dietary habits, and pollution of the living environment. Considering the current state of westernization, this increase in the incidence of breast cancer and the increase in the mortality rate from breast cancer are expected to continue for a considerable period of time in the future.

[0003] As of 2020, more than 2 million people are newly diagnosed with breast cancer in Korea every year, and the prevalence rate is increasing by 5% every year. In surgical procedures for early-stage breast cancer, partial mastectomy (lumpectomy) is gradually increasing, reaching twice the number of total mastectomies as of 2018. In repair surgery after partial mastectomy, the most common methods are to reshape the contralateral breast of the resected breast, insert a prosthesis into the resected breast, or transplant autologous fat harvested from the abdomen. Contralateral breast reshaping is not only expensive, but also has the disadvantage of creating new scars in areas that are not affected by the disease, even though it is a cosmetic surgery that is not related to survival. Even when a prosthesis is inserted to correct the appearance, it is expensive because expensive cadaver-derived dermis is used, and the repair effect is insufficient. Meanwhile, autologous fat transplantation has the disadvantage of the risk of skin-soft tissue fibrosis and adhesion due to radiation therapy, and the cosmetic effect disappears over time as the fat tissue is absorbed after transplantation. Therefore, there is a need to develop new therapeutic approaches that can efficiently and safely reconstruct lost tissue.

[0004] Throughout this specification, a number of papers and patent documents are referenced and citations are displayed, the disclosures of which are incorporated by reference in their entirety into this specification in order to more clearly describe the state of the art and the content of the present invention. Summary of the Invention [Problem to be solved by the invention]

[0005] The present inventors have made extensive research efforts to develop a three-dimensional structure for tissue regeneration that efficiently repairs tissue cavities caused by trauma, surgical resection, etc. As a result, they have found that when a spherical or hemispherical porous structure (scaffold) made of a biocompatible polymer and having an empty interior, specifically a spherical porous structure, is inserted into a collapsed tissue cavity, it has strong physical strength to provide mechanical support for the collapsed space, while being capable of loading an active ingredient that aids in tissue regeneration into the interior space, and not only induces the quantitative recovery of lost tissue, but also decomposes at an appropriate time after insertion, making it useful as a structure for human transplantation for repairing breast tissue, etc., and thus completed the present invention.

[0006] Therefore, an object of the present invention is to provide a three-dimensional structure for tissue regeneration. Another object of the present invention is to provide a composition for reconstructing hollowed out tissue. Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, the claims and the drawings. [Means for solving the problem]

[0007] According to one aspect of the present invention, there is provided a three-dimensional structure (scaffold) for tissue regeneration, comprising: (a) one or more spherical or hemispherical porous surface layers made of a biocompatible polymer; and (b) a cavity formed within said porous surface layer.

[0008] The present inventors have made extensive research efforts to develop a three-dimensional structure for tissue regeneration that efficiently regenerates irreversibly lost tissue, particularly for repairing tissue cavities caused by trauma, surgical resection, etc. As a result, they have found that when a spherical or hemispherical porous structure made of a biocompatible polymer and having an empty space inside, specifically a spherical porous structure, is inserted into a collapsed tissue cavity, it has strong physical strength to provide mechanical support for the collapsed space, while being capable of loading an active ingredient that aids in tissue regeneration into the empty space inside, and not only induces the quantitative recovery of lost tissue, but also decomposes at an appropriate time after insertion, making it useful as a structure for human transplantation to repair various tissues, including breast tissue.

[0009] As used herein, the term "structure" or "scaffold" refers to a tissue engineering structure for promoting the repair and regeneration of damaged tissue by placing biological cells, specifically cells derived from damaged tissue or cells involved in the repair of damaged tissue. Specifically, the structure of the present invention may be a single-layer structure consisting of a single porous sphere, or a multi-layer structure in a core-shell form in which multiple spheres are stacked.

[0010] In this specification, the term "spherical" refers to a three-dimensional figure composed of a collection of points that are the same distance from the center, but the "spherical" surface layer of the present invention does not need to be a geometrically perfect sphere, and includes all structures in which the distance between each point on the strands that make up the surface layer and the center does not exceed a certain range.

[0011] According to a specific embodiment of the present invention, the spherical or hemispherical porous surface layer of the present invention has a geometric structure selected from the group consisting of an icosahedron, a truncated icosahedron and a truncated octahedron.

[0012] According to another embodiment of the present invention, the spherical or hemispherical porous surface layer of the present invention may be a sphere or a shape close to a sphere formed by three-dimensionally molding a planar radial structure, in which case it has a curved surface that is not a polyhedron.

[0013] Most specifically, the spherical or hemispherical porous surface layer of the present invention has the geometry of a truncated icosahedron. As used herein, the term "truncated icosahedron" refers to the soccer ball-shaped polyhedron that would be created if each vertex (corner trisection point) of a regular icosahedron, each face of which is made up of equilateral triangles, were cut open.

[0014] By using such a spherical or nearly spherical geometric scaffold, it can be efficiently inserted into every corner of the recessed space regardless of the shape of the cavity, and can be produced in a standardized manner regardless of the shape or volume of the cavity to be repaired.

[0015] According to a specific embodiment of the invention, the porous surface layer is made of a biocompatible polymer strand. The fibers are crossed, and two or more types of biocompatible polymers can be mixed and used.

[0016] According to the present invention, the surface of the porous sphere (or hemisphere) of the present invention is made by strands having a certain thickness crossing at certain intervals to form pores of a certain size.

[0017] 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, and the role of the support is reduced, and if the diameter is larger than 50 mm, it is difficult to regenerate the tissue, a long period of time is required for biodegradation, and elasticity is reduced. More specifically, the strand has a diameter of 0.5 to 30 mm, 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.

[0018] As used herein, the term "polymer" refers to a synthetic or natural polymeric compound in which monomers of the same or different types are successively linked together. Thus, polymers include homopolymers (polymers in which one type of monomer is polymerized) and hybrid polymers made by polymerization of at least two different monomers, which in turn include copolymers (polymers made from two different monomers) and polymers made from more than two different monomers.

[0019] As used herein, the term "biocompatibility" refers to the property of not causing short-term or long-term side effects when administered into a living body and comes into contact with cells, tissues, or body fluids of an organ, and specifically includes not only tissue compatibility and anticoagulant compatibility, which do not cause necrosis of tissue or coagulation of blood upon contact with biological tissue or blood, but also biodegradability, which disappears after a certain period of time has passed after administration to the body.

[0020] As used herein, the term "biodegradable" refers to the property of being naturally decomposed when exposed to a physiological solution of pH 6-8, specifically, the property of being decomposed over time in a living body by body fluids, decomposing enzymes, microorganisms, etc.

[0021] Biocompatible polymers that can be used in the present invention include PCL [poly(caprolactone)], HEMA [poly(2-hydroxyethyl methacrylate)], PVA (polyvinyl alcohol), PEO (polyethylene oxide), phospholipids, collagen, aliphatic polyethers, 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-lysine), poly(L-glutamic acid), poly(aspartic acid), carboxymethylcellulose, cellulose sulfate, agarose, alginate, carrageenan, hyaluronic acid, dextran, chitosan, poly(hydrogen), and the like. Examples of biocompatible polymers that may be used in the present invention include, but are not limited to, aliphatic polyesters, PLA [poly(lactide)], PGA [poly(glycolide)], PDO [poly(dioxanone)], PBL [poly(butyrolactone)], PVL [poly(valerolactone)], PLG [poly(cyanoacrylic acid)], polyphosphazenes, poly(hydroxyethyl methacrylate), poly(methyl methacrylate), poly(tetrafluoroethylene), poly(dimethylsiloxane), poly(ethylene oxide-β-propylene oxide), poly(vinyl methyl ether), poly(N-alkylacrylamide), decellularized matrix (dECM), and combinations thereof. More specifically, biocompatible polymers that may be used in the present invention include, but are not limited to, aliphatic polyesters, PLA [poly(lactide)], PGA [poly(glycolide)], PDO [poly(dioxanone)], PBL [poly(butyrolactone)], PVL [poly(valerolactone)], PLG [poly(cyanoacrylic acid)], poly(cyanoacrylic acid), ... A [poly(lactide-co-glycolide)], PCL [poly(caprolactone)], or a combination thereof, most specifically PCL [poly(caprolactone)].

[0022] The biocompatible three-dimensional structure of the present invention comprises biocompatible polymer strands coated with collagen.

[0023] In the present specification, the term "coating" means to form a new layer of a certain thickness by modifying a specific substance on a target surface, and the target surface and the coating substance can be modified by ionic or non-covalent bonds. The term "non-covalent bond" is a concept including not only physical bonds such as adsorption, cohesion, entanglement and entrapment, but also bonds that occur by interactions such as hydrogen bonds and van der Waals bonds acting alone or together with the physical bonds. In the present invention, when the collagen solution coats the strands constituting the scaffold, it may form a sealed layer completely surrounding the surface of each strand, or may form a partially sealed layer.

[0024] According to a specific embodiment of the present invention, the structure has a diameter of 3 to 200 mm. If the diameter is less than 3 mm, significant regeneration of adipose tissue is not smooth, and if the diameter is 200 mm or more, it is difficult to insert into a tissue depression.

[0025] More specifically, the structure (scaffold) has a diameter of 10 to 100 mm, more specifically, a diameter of 15 to 50 mm, even more specifically, a diameter of 20 to 40 mm, and most specifically, a diameter of about 30 mm.

[0026] According to another aspect of the present invention, there is provided a composition for reconstructing hollow tissue, comprising the above-mentioned scaffold of the present invention; and collagen, adipose tissue, mammary gland tissue, or a combination thereof as an active ingredient.

[0027] As described above, the scaffold of the present invention can be loaded with an active ingredient that helps regenerate tissues, including collagen, adipose tissue, and mammary gland tissue, in the empty space inside. Such active ingredients for tissue regeneration can be appropriately selected, including collagen, adipose tissue, and mammary gland tissue, as well as cells or tissue mass derived from the tissue, depending on the characteristics of the tissue to be regenerated. In addition, the active ingredient that helps regenerate tissue may be implanted into the lesion while still filled in the internal space of the scaffold of the present invention, or may be implanted into the lesion first and then filled in the internal space of the scaffold before suturing.

[0028] As used herein, the term "transplantation" refers to the process of transferring living tissues, cells, active ingredients that aid in tissue regeneration, or artificial supports that receive them from a donor to a recipient with the aim of maintaining the functional integrity of the transplanted tissues or cells in the recipient. Thus, the term "transplant support" refers to a physical support used in the process of transferring living tissues or cells to a recipient.

[0029] According to a particular embodiment of the invention, said hollowed out tissue is adipose tissue or fibrous tissue, more particularly said adipose tissue is breast adipose tissue.

[0030] According to yet another aspect of the present invention, there is provided a radial porous mesh made of a biocompatible polymer for forming the above-mentioned three-dimensional scaffold for tissue regeneration of the present invention. The porous mesh of the present invention has a radial shape extending from a center. By forming a mesh having a large number of straight lines into a spindle shape in a radial manner and molding the corresponding ends of the mesh into a round sphere, the above-mentioned "spherical porous surface layer having a cavity" of the present invention can be formed.

[0031] According to a specific embodiment of the present invention, the porous mesh may include a fixing portion and a fixing portion receiving portion at both ends facing each other with respect to the center of the radial shape. In this way, the corresponding ends of the linear mesh extending from the center in a radial shape are mechanically connected via the fixing portion and the fixing portion receiving portion, respectively, so that the spherical porous surface layer becomes stronger. The fixing portion and the fixing portion receiving portion may be formed only at one pair of corresponding ends (left side of FIG. 2C), may be formed at multiple pairs of corresponding ends, or may be formed at all pairs of corresponding ends (right side of FIG. 2C).

[0032] In addition, when a fixing portion is formed at one end, a fixing portion accommodating portion may be formed not only at the end corresponding to the fixing portion but also at all remaining ends, thereby allowing one fixing portion to be coupled to multiple fixing portion accommodating portions (left side of Figure 2C).

[0033] According to yet another specific embodiment, the porous mesh has n ends extending from the center of the radial shape, of which n-1 ends include a fixing portion or a fixing portion receiving portion, and one end can include n-1 fixing portion receiving portions or fixing portions capable of forming bonds with the fixing portions or fixing portion receiving portions included in the remaining n-1 ends (middle of Figure 2C).

[0034] The fastening portion and fastening portion receiving portion may be, for example, but are not limited to, a hook and a hook receiving portion, respectively, and any fastening means capable of forming a mechanical connection and securing the formed connection is applicable.

[0035] According to yet another aspect of the present invention, the present invention provides a method for reconstructing hollow tissue of a subject, comprising transplanting the above-mentioned scaffold of the present invention; and collagen, adipose tissue, mammary gland tissue, or a combination thereof into the hollow tissue of a subject.

[0036] The scaffold, collagen, adipose tissue and mammary tissue used in the present invention have already been described in detail, so their description will be omitted to avoid excessive duplication. Effect of the Invention

[0037] The features and advantages of the present invention can be summarized as follows: (a) The present invention provides a biocompatible three-dimensional scaffold and a composition for reconstructing hollow tissue comprising the same. (b) The present invention has strong physical strength and provides mechanical support for the recessed space, while allowing the internal space to be filled with an active ingredient for tissue regeneration, thereby efficiently inducing quantitative recovery of irreversibly lost tissue. (c) The present invention also uses a spherical scaffold that can be efficiently inserted into any shape of depressed area and can be usefully used as a scaffold for human transplantation to repair various adipose tissues, including breast tissue, by decomposing at an appropriate time after regeneration is completed. [Brief description of the drawings]

[0038] [Figure 1] FIG. 1 is a schematic diagram showing the process of partial repair of lost breast tissue by applying the biocompatible three-dimensional structure of the present invention. By inserting the structure of the present invention into the cavity that occurs after partial mastectomy, the sunken breast can be repaired. [Figure 2A] FIG. 2 shows structural diagrams of the biocompatible three-dimensional structures of the present invention having various strand morphologies, each of which is a schematic diagram of a sphere (FIG. 2A), a hemisphere (FIG. 2B), and a radial structure for forming a spherical structure (FIG. 2C). [Figure 2B] FIG. 2 shows structural diagrams of the biocompatible three-dimensional structures of the present invention having various strand morphologies, each of which is a schematic diagram of a sphere (FIG. 2A), a hemisphere (FIG. 2B), and a radial structure for forming a spherical structure (FIG. 2C). [Figure 2C] FIG. 2 shows structural diagrams of the biocompatible three-dimensional structures of the present invention having various strand morphologies, each of which is a schematic diagram of a sphere (FIG. 2A), a hemisphere (FIG. 2B), and a radial structure for forming a spherical structure (FIG. 2C). [Figure 3A] Figure 3 shows micro-CT images taken of the transverse section (Figure 3A) and longitudinal section (Figure 3B) of the transplant site 2 months, 4 months, and 6 months after the biocompatible three-dimensional support of the present invention was transplanted into a rat model, and the results of H&E staining and Masson's trichrome staining of the tissue at the transplant site that was sliced ​​transversely. [Figure 3B] Figure 3 shows micro-CT images taken of the transverse section (Figure 3A) and longitudinal section (Figure 3B) of the transplant site 2 months, 4 months, and 6 months after the biocompatible three-dimensional support of the present invention was transplanted into a rat model, and the results of H&E staining and Masson's trichrome staining of the tissue at the transplant site that was sliced ​​transversely. [Figure 4] Figure 4 shows the results of H&E staining and Masson's trichrome staining of tissue sections from the transplanted site three months after the biocompatible three-dimensional support of the present invention was transplanted into a pig model. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0039] The present invention will be described in more detail with reference to the following examples. It will be obvious to those skilled in the art that these examples are merely for the purpose of illustrating the present invention in more detail, and that the scope of the present invention is not limited to these examples according to the gist of the present invention.

[0040] Working Example Manufacturing Example 1: Manufacturing of biocompatible three-dimensional structures A 3D printer (RAISE 3D, USA) was used to fabricate the three-dimensional polymer structure. The 3D printing method allows the size of the three-dimensional structure to be easily adjusted by conditions such as nozzle diameter, temperature, discharge pressure, and nozzle movement speed. The inventors fabricated a three-dimensional structure with an overall spherical shape by geometrically intersecting strands with a diameter of 1 mm in order to occupy the volume of the lost part in the tissue while having high mechanical elasticity. Polycaprolactone (PCL, Polycaprolactone, Sigma-Aldrich, USA) was used as the raw polymer, and the nozzle diameter was set to 0.4 mm, the nozzle temperature to 130 °C, the output speed to 5 mm / s, and the nozzle movement speed to 40 mm / s to fabricate the polymer mesh. When the setting was completed, a three-dimensional structure with a truncated icosahedral structure with a diameter of 1 cm and a strand thickness of 1 mm was fabricated. Thereafter, it was sterilized with e-beam before use in the experiment. The three-dimensional polymer structure that was created forms a spherical structure with a hollow interior, with meshes of various shapes formed on the surface as the strands cross in various ways (Figure 2).

[0041] Manufacturing Example 2: Manufacturing of collagen-coated biocompatible three-dimensional structures The biocompatible three-dimensional structure produced in Production Example 1 was further coated with collagen using a collagen solution. Atelocollagen (type 1, medical grade collagen) extracted from porcine dermis was used. A collagen solution was prepared by dissolving 0.5% collagen (medical grade, Dalim Tissen, Korea) in 0.5 M acetic acid at 4° C. for 12 hours.

[0042] To coat the collagen uniformly, the strongly hydrophobic polycaprolactone was treated with plasma to make it hydrophilic. The polycaprolactone 3D structure was placed on a glass Petri dish and treated with a plasma surface treatment machine (PDC-32G-2 Plasma, Harrick Plasma, USA) for 60 seconds under vacuum conditions of 1.0-0.1 Torr.

[0043] After the surface treatment process, the 3D structure was placed on a plate of a certain height, and the collagen solution was poured in so that the 3D structure was fully immersed, and the coating process was carried out for 30 minutes at 4°C. After the coating process, the sample was cooled to -50°C for 3 hours, and then dried for 14 hours using a freeze dryer (MG-VFD5, MG Indus., Korea) to create a porous surface structure of the collagen coated on the surface.

[0044] Then, a neutralization process was carried out to remove acetic acid present in the form of salt inside the freeze-dried collagen. For this, the freeze-dried specimen was washed four times for 15 minutes using absolute alcohol (Ethanol Absolute, Merck KGaA, Germany), and then neutralized with acetic acid by dissolving 0.5M NaOH (Duksan General Science, Korea) in 70% ethanol for 15 minutes four times. Then, to remove the residual NaOH present in the specimen, it was washed four times for 15 minutes using 50% and 30% ethanol and triple distilled water. After washing, the collagen-coated 3D structure was cooled to -50°C for 3 hours and then dried using a freeze dryer for 12 hours as mentioned above. Then, it was sterilized with e-beam before being used in the experiment.

[0045] The three-dimensional polymer structure thus fabricated is a spherical structure with a hollow interior, in which the strands cross in various ways, forming meshes of various shapes on the surface.

[0046] Experimental example 1: Rat model animal experiment The present inventors attempted to evaluate whether the introduction of the three-dimensional polymer structure of the present invention can be applied to tissue regeneration, for example, partial breast reconstruction surgery. The rats were divided into four groups, including a group in which about 50% of the tissue in the mammary gland area of ​​SD rats (8 weeks old, female) was excised with surgical scissors and then sutured, a group in which about 50% of the tissue in the mammary gland area was excised with surgical scissors and then the three-dimensional structure (PCL ball) of Preparation Example 1 was transplanted into the excised mammary gland tissue area and then sutured, a group in which about 50% of the tissue in the mammary gland area was excised with surgical scissors and then the three-dimensional structure (PCL-col ball) of Preparation Example 2 was transplanted and a collagen preparation was injected into the three-dimensional structure and then sutured, and a group in which about 50% of the tissue in the mammary gland area was excised with surgical scissors and then the three-dimensional structure of Preparation Example 2 was transplanted, and mouse mammary gland tissue was sandwiched in the three-dimensional structure and then sutured, and the experiment was carried out.

[0047] At 2, 4, and 6 months after suturing, the transplantation site was photographed using a micro-CT (Quantum GX2 microCT Imaging System, PerkinElmer), and each experimental animal was sacrificed to extract tissue from the area where the three-dimensional structure was transplanted, which was then sectioned vertically or horizontally and stained with H&E (hematoxylin&eosin) and Masson's trichrome. As a result, as shown in Figures 3A and 3B, the micro-CT images taken at 2, 4, and 6 months for a mouse in which about 50% of the mammary tissue was removed and no treatment was performed showed that the lost tissue was not restored at all, whereas the micro-CT images taken at 2, 4, and 6 months for a mouse in which the three-dimensional structure of the present invention was transplanted confirmed that tissue was significantly formed within the three-dimensional structure over time. It was confirmed that in the group in which the collagen preparation was injected into the 3D structure after transplantation of the 3D structure, tissue was continuously maintained within the 3D structure, which was detected as opaque on micro-CT. In the group in which the mouse mammary tissue was filled and sutured after transplantation of the 3D structure, it was confirmed that tissue gradually grew within the structure over time. H&E staining confirmed that tissue was generated in the internal cavity in all cases where only the 3D structure was transplanted, where the 3D structure injected with the collagen preparation was transplanted, and where the 3D structure inserted with the mammary tissue was transplanted. In particular, it was observed that adipose tissue was generated and entered from the periphery of the structure into the interior in the group in which the 3D structure was transplanted, and that fibrous tissue was regenerated in the 3D structure injected with the collagen preparation. It was also observed that in the 3D structure inserted with the mammary tissue, the mammary tissue was well maintained within the structure, and regenerated in a form in which fibrous tissue surrounded the periphery of the mammary tissue.

[0048] In addition, Masson's trichrome staining was used to observe that more collagen was produced inside the 3D structure injected with the collagen preparation than inside the 3D structure, and considering that the injected collagen is usually broken down within 1-2 months, it was confirmed that fibrous tissue was formed by the injected collagen, and that tissue was constructed and repaired by collagen secreted from the fibrous tissue by the 6th month. Furthermore, it was found that the remaining tissues, excluding the mammary gland tissue, inside the 3D structure into which the mammary gland tissue was inserted were fibrous tissues made of collagen.

[0049] Experimental example 2: Pig model animal experiment To prepare a partial mastectomy model in minipigs, 12-month-old adult minipigs were bred in an SPF breeding facility. After a one-week acclimatization period, anesthesia was induced by intramuscular injection of 1 mg / kg alfaxane and 2 mg / kg xylazine, and then anesthesia was maintained during surgery by respiratory anesthesia with 2% isoflurane. The surgical site of the minipigs was sterilized with 70% ethanol and iodine, and 15 ml of mammary tissue was partially excised to prepare a partial mastectomy model. The three-dimensional structures of Production Example 1 (PCL ball) and Production Example 2 (PCL-col ball) were transplanted into the partially excised surgical site and then sutured. Thereafter, 20 mg / kg cefazolin and 0.4 mg / kg meloxicam were intramuscularly injected for three days. Three months after the operation, the minipig was sacrificed by injecting KCL under general anesthesia to obtain the transplanted PCL and PCL-col balls. After that, it was washed three times with PBS (phosphate-buffered saline) and treated with 10% formalin solution to fix the cells and tissues. Then, H&E (hematoxylin & eosin) staining and Masson's trichrome staining were performed to confirm the characteristics of the fixed tissue. As a result, as shown in Figure 4, it was confirmed that tissues derived from the inside of the minipig individual flowed into and were generated inside the PCL and PCL-col balls three months after transplantation into the partial mastectomy model. In addition, in the group transplanted with the PCL ball, a small amount of fibrous tissue was generated inside the PCL ball, confirming the flow of autologous mammary gland tissue from the outside, and in the group transplanted with PCL-col, it was confirmed that a large amount of fibrous tissue was generated inside the PCL-col ball, confirming that autologous mammary gland tissue hardly flowed in from the outside.

[0050] Although certain parts of the present invention have been described in detail above, it is obvious to those skilled in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of the present invention. Therefore, the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. 3D scaffolds for tissue regeneration, including: (a) one or more spherical or hemispherical porous surface layers of a biocompatible polymer; and (b) a cavity formed within the porous surface layer.

2. The scaffold of claim 1 , wherein the porous surface layer is formed by crossing biocompatible polymer strands.

3. The biocompatible polymer may be PCL [poly(caprolactone)], HEMA [poly(2-hydroxyethyl methacrylate)], PVA (polyvinyl alcohol), PEO (polyethylene oxide), phospholipids, collagen, aliphatic polyesters, PLA [poly(lactide)], PGA [poly(glycolide)], PDO [poly(dioxanone)], PBL [poly(butyrolactone)], PVL [poly(valerolactone)], PLGA [poly(lactide-co-glycolide)], polyurethane, pibronectin, vitronectin, poly-L-lysine, poly-L-glutamic acid, polyaspartic acid, carboxymethylcellulose, cellulose sulfate, agarose, or the like.

2. The scaffold of claim 1, wherein the polysaccharide is selected from the group consisting of cellulose, alginate, carrageenan, hyaluronic acid, dextran, chitosan, poly(hydroxybutyrate), poly(alkylene succinate), polyamide, polyanhydride, poly(orthoester), poly(cyanoacrylic acid), polyphosphazene, poly(hydroxyethyl methacrylate), poly(methyl methacrylate), poly(tetrafluoroethylene), polydimethylsiloxane, poly(ethylene oxide-β-propylene oxide), poly(vinyl methyl ether), poly(N-alkylacrylamide), decellularized matrix, and combinations thereof.

4. 4. The scaffold of claim 3, wherein the biocompatible polymer is PCL [poly(caprolactone)].

5. The scaffold of claim 2, wherein the strands have a diameter of 0.1 to 50 mm.

6. The scaffold of claim 5 , wherein the strands are coated with collagen.

7. The scaffold of claim 1, wherein the scaffold has a diameter of 3 to 200 mm.

8. 2. The scaffold of claim 1, wherein the spherical or hemispherical porous surface layer has a geometric structure selected from the group consisting of a regular icosahedron, a truncated icosahedron, and a truncated octahedron.

9. The scaffold according to claim 1 , wherein the spherical or hemispherical porous surface layer is formed by three-dimensionally molding a planar radial structure.

10. A composition for reconstructing hollow tissue, comprising the scaffold according to any one of claims 1 to 9; and collagen, adipose tissue, mammary gland tissue, or a combination thereof as an active ingredient.

11. The composition of claim 10, wherein the hollowed out tissue is adipose tissue or fibrous tissue.

12. The composition of claim 11, wherein the adipose tissue is breast adipose tissue.

13. A radial porous mesh made of a biocompatible polymer for forming a three-dimensional scaffold for tissue regeneration according to claim 1.

14. The porous mesh according to claim 13, wherein the porous mesh includes a fixing portion and a fixing portion receiving portion at both positions facing each other with respect to the center of the radial shape.

15. The porous mesh of claim 13, wherein the porous mesh has n ends extending from the center of the radial shape, of which n-1 ends include fixing portions or fixing portion receiving portions, and one end includes n-1 fixing portion receiving portions or fixing portions that can form bonds with the fixing portions or fixing portion receiving portions included in the remaining n-1 ends.

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