Artificial implant with improved biocompatibility through surface treatment

Abstract

An embodiment of the present specification provides an artificial implant comprising: an implant body; and a coating layer formed on at least part of the surface of the implant body, wherein the coating layer comprises decellularized tissue.

Description

Artificial implants with improved biocompatibility through surface treatment

[0001] The present invention relates to an artificial implant that provides excellent safety within the human body and can prevent capsular contracture by coating the surface to impart hydrophilicity.

[0002] Artificial implants are Class 4 medical devices that exist within the body and are applied to various parts of the body, such as the nose and breasts. In particular, most artificial implants are in the form of a silicone shell that forms the outer surface of the implant, filled with a gel or saline solution of appropriate viscosity, and thus require exceptional stability within the body.

[0003] Therefore, the implant industry has secured the physical properties required for medical devices by methods such as adjusting the thickness of the silicone shell or modifying the composition of the filler, and research and development is generally underway to achieve natural shapes by controlling the physical properties of the filler.

[0004] However, if commercially available implants are used, they may not be properly fixed to the body, causing a foreign body sensation. Also, because they are not designed to fit the body's internal space, the implant may shift within the body, creating a void where blood or pus accumulates, which can lead to a seroma.

[0005] In addition, silicone implants inserted into the body are considered foreign substances, and a fibrous membrane forms around them. If this membrane becomes excessively thick, it can become stiff and lead to capsular contracture.

[0006] In this regard, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is also continuously being reported, which necessitates surgery when capsular contracture exceeding a certain thickness occurs and can even lead to the user's death.

[0007] Such capsular contracture occurs due to various causes, but the frequency of occurrence varies significantly depending on the characteristics of the shell, which is the outer part of the implant that comes into direct contact with and reacts with body tissues after implantation.

[0008] Currently, many attempts are being made to improve these problems by modifying the surface structure and composition to impart hydrophilicity, but there are limitations to reducing spherical formation through such attempts alone.

[0009] For example, a new surgical method involving wrapping an implant with an acellular dermal matrix (ADM) is being used, but this method has limitations, including being very expensive and requiring reprocessing in the operating room to fit the shape of the implant.

[0010] In addition, surrounding tissues may be damaged due to cavities or incisions created during the implantation process, and side effects such as an increased probability of inflammation resulting from this damage are also occurring.

[0011] Therefore, there is a need for the development of new artificial implants that can effectively prevent capsular contracture when implanted in the human body.

[0012] The present invention is intended to solve the problems revealed in the aforementioned prior art, and one of the various objectives of the present invention is to provide an artificial implant in which the surface of the artificial implant is coated with a biocompatible material, thereby having high hydrophilicity, a low likelihood of inflammation, and a low likelihood of capsular contracture.

[0013] According to one aspect, an artificial implant is provided, comprising: an implant body; and a coating layer formed on at least a portion of the surface of the implant body, wherein the coating layer comprises decellularized tissue.

[0014] In one embodiment, the decellularized tissue may be obtained by decellularizing muscle tissue, skin tissue, or adipose tissue.

[0015] In one embodiment, the coating layer may further include an additive.

[0016] In one embodiment, the additive may be at least one or two or more selected from the group consisting of silicone elastomer, PCL (polycaprolactone), PLA (polylactic acid), PLCL (poly-lactide-co-ε-caprolactone), PLLA (poly-L-lactic acid), PGA (polyglycolic acid), PLGA (poly-co-glycolic-acid), PHA (polyhydroxyalkanoate), PDO (polydioxanone), hyaluronic acid, collagen, and gelatin.

[0017] In one embodiment, the coating layer may have a content ratio of the additive to the decellularized tissue of 0.004 or more and 150 or less.

[0018] In one embodiment, the thickness of the coating layer may be 0.01mm to 10mm.

[0019] In one embodiment, the external surface contact angle of the artificial implant may be 120° or less.

[0020] In one embodiment, the decellularized tissue comprises water, organic matter, and inorganic matter, and may contain at least 30 parts by weight of the organic matter for every 100 parts by weight of the total of the organic matter and inorganic matter.

[0021] In one embodiment, the organic material may be at least one selected from the group consisting of collagen, elastin, proteoglycan, and laminin.

[0022] An artificial implant according to one aspect of the present invention has the advantage of having high biocompatibility due to the hydrophilicity imparted to its surface and a significantly low incidence of capsular contracture due to reduced inflammatory response.

[0023] The effects of one aspect of the present invention are not limited to the effects described above, and should be understood to include all effects that can be inferred from the configurations described in the detailed description of the invention or the claims of this specification.

[0024] Figure 1 is a graph showing the surface contact angle according to the surface roughness value of the artificial implant of the present invention.

[0025] Figure 2 shows experimental data on the effect of inhibiting capsular contracture of the artificial implant of the present invention, where (a) is a graph of interferon-γ factor concentration and (b) shows the thickness of the formed film.

[0026] Hereinafter, one aspect of the present specification will be described with reference to the attached drawings. However, the details described in the present specification may be implemented in various different forms and are therefore not limited to the embodiments described herein.

[0027] Throughout the specification, when a part is described as "including" a certain component, this means that, unless specifically stated otherwise, it does not exclude other components but rather allows for the inclusion of additional components.

[0028] When a range of numerical values ​​is described in this specification, unless a specific range is otherwise described, the value has the precision of significant figures provided according to the standard rules in chemistry for significant figures. For example, 10 includes a range of 5.0 to 14.9, and the number 10.0 includes a range of 9.50 to 10.49.

[0029] artificial implants

[0030] An artificial implant according to one aspect of the present invention comprises: an implant body; and a coating layer formed on at least a portion of the surface of the implant body.

[0031] The implant body is a two-dimensional or three-dimensional structure composed mainly of a skeletal structure, and may be a two-dimensional planar structure or a three-dimensional structure with a cross section selected from a circular, oval, or teardrop shape, but is not limited thereto.

[0032] The implant body may consist of a shell and a filler filled inside the shell, in which case the shell may be a silicone shell and the filler may be a silicone gel. The silicone gel may be a polyorganosiloxane.

[0033] The above-mentioned organosiloxane polymer may be one selected from the group consisting of dimethylsiloxane, methylhydrogensiloxane, methylphenylsiloxane, diphenylsiloxane, dimethylvinylsiloxane, trifluoropropylsiloxane, and mixtures of two or more of these, but the type is not particularly limited as long as the functional characteristics of the artificial implant can be realized.

[0034] Alternatively, the implant body may be formed as an integral structure that does not include a separate shell, and in this case, the implant body may include a biodegradable polymer.

[0035] The above biodegradable polymer may include one or more selected from the group consisting of PCL (polycaprolactone), PLCL (poly-lactide-co-ε-caprolactone), PLA (polylactic acid), PLLA (poly-L-lactic acid), PGA (polyglycolic acid), PLGA (poly-co-glycolic-acid), PHA (polyhydroxyalkanoate), and PDO (polydioxanone), and preferably, the biodegradable polymer may be PCL (polycaprolactone), but is not limited thereto.

[0036] When using PCL with a number average molecular weight (Mn) of 45,000 to 80,000 as the above-mentioned biodegradable polymer, there are additional advantages such as excellent moldability and biodegradability, which results in superior biocompatibility when the artificial implant is applied to the body, improved tissue responsiveness, prevention of implant displacement due to improved adhesion, and significantly reduced risk of capsular contracture and seroma formation.

[0037] The coating layer is formed on at least a portion of the surface of the implant body and comprises decellularized tissue. Here, “decellularized tissue” generally refers to any tissue that does not substantially contain cells and / or cellular components.

[0038] For example, soft tissues such as skin, parts of the skin (e.g., dermis), blood vessels, heart valves, fascia, cartilage, adipose tissue, and neural connective tissue may all be used to produce the decellularized tissue. Preferably, the decellularized tissue may be obtained by decellularizing muscle tissue, skin tissue, or adipose tissue. Most preferably, the decellularized tissue may be acellular dermal tissue (ADM).

[0039] Here, “acellular dermal tissue” may be human-derived allogeneic or animal-derived xenogeneic dermal tissue, and preferably may be human-derived acellular allogeneic dermal tissue, but is not limited thereto. The acellular dermal tissue is a dermal layer obtained by chemically treating isolated dermis to remove cells capable of causing an immune rejection reaction, and mainly contains collagen and elastin.

[0040] The above-mentioned acellular dermal tissue may be used in particle form or sheet form, but is not limited thereto. If the above-mentioned acellular dermal tissue is granulated to form a microstructure, it can be used as a particle-type acellular dermal tissue, and if cells are removed while maintaining the sheet-type dermal tissue structure, it can be used as a sheet-type acellular dermal tissue for skin grafting, etc.

[0041] Particulate acellular dermal tissue is often used as a skin substitute after freeze-drying and hydrating with saline or distilled water. Because it can maintain a fluid state, it has the advantage of being able to be injected using a syringe without surgery. Therefore, it is used for various tissue repairs, such as treating skin tissue defects caused by accidents as well as treating chronic diseases like diabetic ulcers.

[0042] In addition, since particulate acellular dermal tissue is used as a filler in the plastic surgery market as a safe and effective biomaterial, it can be used to increase the hydrophilicity of artificial implants without rejection reactions within the tissue.

[0043] If the above-mentioned acellular dermal tissue is a particulate acellular dermal tissue, it may have a particle size of about 300-800 μm, and preferably a particle size of about 450-650 μm.

[0044] If the particle size of the above-mentioned particulate acellular dermal tissue is less than the above range, the rate of biodegradation of the dermal tissue is further accelerated due to the influence of the protein-degrading enzyme collagenase (Matrix Metalloproteinase, MMP-1), which may shorten the time of preservation of the coating layer in the body after inserting the artificial implant, and if the particle size of the above-mentioned particulate acellular dermal tissue exceeds the above range, the coating on the surface of the artificial implant may not be formed smoothly.

[0045] The above-mentioned decellularized tissue may undergo experiments to confirm whether it substantially contains no cells or cellular components. For example, the processed tissue may be examined by light microscopy to determine whether cells or cellular components remain, and DNA or other nucleic acid analyzers may be used to check for the presence of residual nuclear material within the tissue matrix. Finally, the cell-free status of the tissue matrix can be verified through analytical methods that identify cell-specific components, such as surface antigens.

[0046] The above-mentioned decellularized tissue is composed of water, minerals, and organic matter, but the minerals are unlikely to contribute to securing hydrophilicity. Meanwhile, the higher the proportion of protein contained in the organic matter, the more advantageous it may be for securing hydrophilicity and improving biocompatibility.

[0047] Accordingly, the decellularized tissue may contain at least 30 parts by weight of the organic material with respect to 100 parts by weight of the total of the organic and inorganic materials, preferably at least 40 parts by weight, more preferably at least 50 parts by weight, and most preferably at least 60 parts by weight, but is not limited thereto.

[0048] The above organic material may be at least one selected from the group consisting of collagen, elastin, proteoglycan, and laminin, and preferably the organic material may be collagen, but is not limited thereto.

[0049] The aforementioned collagen, elastin, proteoglycans, and laminin are components abundant in connective tissue and epithelial tissue, and are constituent proteins that make up the extracellular matrix.

[0050] If the above organic material is at least one selected from the group consisting of collagen, elastin, proteoglycan, and laminin, the outer surface of the artificial implant may be sufficiently hydrophilic, thereby improving biocompatibility.

[0051] In addition, the coating layer may further include additives. The additives may be used to reinforce the hydrophilicity of the coating layer, and accordingly, biocompatibility may be increased upon implantation of the artificial implant, and the incidence of capsular contracture may be reduced.

[0052] The above additive may be one or more selected from the group consisting of silicone elastomer, PCL (polycaprolactone), PLCL (poly-lactide-co-ε-caprolactone), PLA (polylactic acid), PLLA (poly-L-lactic acid), PGA (polyglycolic acid), PLGA (poly-co-glycolic-acid), PHA (polyhydroxyalkanoate), PDO (polydioxanone), hyaluronic acid, collagen, and gelatin, and preferably the additive may be hyaluronic acid or PCL (polycaprolactone), but is not limited thereto.

[0053] When hyaluronic acid is used as the above additive, due to the excellent moisturizing properties of hyaluronic acid, which has a water content of 50 to 200 times, it is advantageous for imparting hydrophilicity, so when the artificial implant is applied in the body, biocompatibility can be greatly improved, tissue responsiveness can also be excellent, and the possibility of capsular contracture can also be lowered.

[0054] In addition, if PCL with a number average molecular weight (Mn) of 45,000 to 80,000 is used as the above additive, the moldability and biodegradability are excellent, so the biocompatibility can be greatly improved when the artificial implant is applied in the body, tissue responsiveness can also be excellent, and the possibility of capsular contracture and seroma development can also be reduced.

[0055] The coating layer may have a content ratio of the additive to the decellularized tissue of 0.004 or more and 150 or less, preferably 0.01 or more and 50 or less, and most preferably 0.04 or more and 10 or less.

[0056] For example, the coating layer has a content ratio of the additive to the decellularized tissue of 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, It may be 85, 90, 95, 100, 110, 120, 130, 140, 150, or a value between two of these values, but is not limited thereto.

[0057] If the coating layer contains the additive, its hydrophilicity increases, which may be more advantageous in terms of biocompatibility. However, if the content is excessive, it may be difficult to secure the physical properties of the coating layer, and consequently, workability may be reduced when manufacturing artificial implants.

[0058] The thickness of the coating layer may be 0.01mm to 10mm. For example, the thickness of the coating layer is 0.01mm, 0.02mm, 0.03mm, 0.04mm, 0.05mm, 0.06mm, 0.07mm, 0.08mm, 0.09mm, 0.1mm, 0.2mm, 0.3mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm, 1.0mm, 1.5mm, 2.0mm, 2.5mm, 3.0mm, 3.5mm, 4.0mm, 4.5mm, 5.0mm, 5.5mm, 6.0mm, 6.5mm, 7.0mm, 7.5mm, 8.0mm, 8.5mm, 9.0mm, 9.5mm, 10mm, or a value between two of these values. It is possible.

[0059] If the thickness of the coating layer is less than the above range, the coating function of the acellular dermis is not sufficiently exerted, making it difficult to secure hydrophilicity, and if the thickness of the coating layer exceeds the above range, the coating becomes excessively thick, which may adversely affect the tactile sensation of the implant and further increase the likelihood of capsular contracture.

[0060] The average contact angle of the outer surface of the artificial implant may be 120° or less, preferably 90° or less, and most preferably 60° or less. Here, the “average contact angle” is an indicator for measuring the degree of hydrophilicity of a specific surface and refers to the angle formed by the tangent between the bottom surface and the water droplet on the specific surface. The average contact angle is an average value based on measurement and is determined by the surface tension between the water and the bottom surface. Additionally, the more hydrophilic the surface of the material, the flatter the shape forms, which can result in a smaller average contact angle.

[0061] For example, the average contact angle of the outer surface of the artificial implant is 120°, 119°, 118°, 117°, 116°, 115°, 114°, 113°, 112°, 111°, 110°, 109°, 108°, 107°, 106°, 105°, 104°, 103°, 102°, 101°, 100°, 99°, 98°, 97°, 96°, 95°, 94°, 93°, 92°, 91°, 90°, 89°, 88°, 87°, 86°, 85°, 84°, 83°, 82°, 81°, 80°, 79°, 78°, 77°, 76°, 75°, 74°, 73°, 72°, 71°, 70°, 69°, 68°, 67°, 66°, 65°, 64°, 63°, 62°, 61°, 60°, 59°, 58°, 57°, 56°, 55°, 54°, 53°, 52°, 51°, 50°, 49°, 48°, 47°, 46°, 45°, 44°, 43°, 42°, 41°, 40°, 39°, 38°, 37°, 36°, 35°, 34°, 33°, 32°, 31°, 30°, 29°, 28°, 27°, 26°, 25°, 24°, 23°, 22°, 21°, 20°, 19°, 18°, 17°, 16°, 15°, 14°, 13°, 12°, 11°, 10°, 9°, 8°, 7°, 6°, 5°, 4°, 3°, 2°, 1° or a value between two of these values.

[0062] If the average contact angle of the outer surface satisfies the above range, there is an advantage that when the artificial implant is inserted into the body, it adheres well to blood or intracellular fluid, thereby lowering the possibility of capsule formation or ALCL development.

[0063] On the other hand, if the average contact angle of the outer surface exceeds the above range, hydrophilicity is not ensured, resulting in low wettability to body fluids and tissues, and tissue reactivity (cell adhesion ability) may not be sufficiently ensured. Consequently, the artificial implant may be recognized as a foreign substance within the body, which may lead to a decrease in the rate of tissue regeneration or an increased likelihood of capsular contracture.

[0064] The outer surface of the above artificial implant has a square root mean height value (S q The thickness may be 0.01 to 50 μm, preferably 0.1 to 35 μm, and most preferably 1 to 20 μm, but is not limited thereto.

[0065] Here, "square root mean height (S q )” refers to the average value obtained by squaring the average height from the reference plane to the surface. In addition, the square root average height value (S q ) may be defined according to ISO 25178-2:2030 standards.

[0066] For example, the outer surface of the artificial implant has a square root mean height value (S q) 0.01μm, 0.02 μm, 0.03 μm, 0.04 μm, 0.05μm, 0.06μm, 0.07μm, 0.08μm, 0.09μm¸0.1μm, 0.2μm, 0.3μm, 0.4μm, 0.5μm, 0.6μm, 0.7μm, 0.8μm, 0.9μm, 1μm, 2μm, 3μm, 4μm, 5μm, 6μm, 7μm, 8μm, 9μm, 10μm, 11μm, 12μm, 13μm, 14μm, 15μm, 16μm, 17μm, 18μm, 19μm, It may be 20μm, 21μm, 22μm, 23μm, 24μm, 25μm, 26μm, 27μm, 28μm, 29μm, 30μm, 31μm, 32μm, 33μm, 34μm, 35μm, 36μm, 37μm, 38μm, 39μm, 40μm, 41μm, 42μm, 43μm, 44μm, 45μm, 46μm, 47μm, 48μm, 49μm, 50μm, or a value between two of these values.

[0067] The square root mean height value (S) of the outer surface of the above artificial implant q If ) is below the above range, sufficient hydrophilicity may not be ensured, and biocompatibility may not be ensured; consequently, the rate of tissue regeneration may be reduced, or the likelihood of capsular contracture may increase. The square root mean height value (S) of the outer surface of the artificial implant q If this exceeds the above range, the surface becomes excessively rough, which may increase the likelihood of spherical contracture, seroma, and anaplastic large cell lymphoma (BIA-ALCL).

[0068] The tensile strength of the coating layer may be 10 to 30 MPa. For example, the tensile strength of the coating layer may be 10 MPa, 11 MPa, 12 MPa, 13 MPa, 14 MPa, 15 MPa, 16 MPa, 17 MPa, 18 MPa, 19 MPa, 20 MPa, 21 MPa, 22 MPa, 23 MPa, 24 MPa, 25 MPa, 26 MPa, 27 MPa, 28 MPa, 29 MPa, 30 MPa, or a value between two of these values.

[0069] If the tensile strength of the coating layer exceeds the above range, the strength may be excessively high, increasing the likelihood of spherical contracture; if it is below the above range, the strength may be low, failing to meet the standard physical properties of the artificial implant.

[0070] The above coating layer may be formed by contacting a coating solution, in which decellularized tissue, etc. is dissolved in a solvent, with at least a portion of the surface of the implant body and then drying it, but is not limited thereto.

[0071] The above solvent may be one or more selected from the group consisting of distilled water, physiological saline, PBS (phosphate buffered saline), dextran solution, PEG (Polyethyleneglycol) solution, glycerol, and HEPES Buffer solution, and preferably may be physiological saline, but is not limited thereto.

[0072] The above solvent may further include one or more selected from the group consisting of xylene, toluene, and ethanol, and preferably may include xylene, but is not limited thereto.

[0073] When physiological saline and xylene are used as the above solvents, the decellularized tissue is stabilized, which has the advantage of improving workability during the coating of the artificial implant, but is not limited thereto.

[0074] Method for manufacturing artificial implants

[0075] The method for manufacturing an artificial implant will be described in detail below. However, the description of parts within the same scope as the artificial implant will be omitted.

[0076] A method for manufacturing an artificial implant according to another aspect of the present invention comprises the steps of: (a) dissolving decellularized tissue in a solvent to prepare a coating solution; and (b) contacting the coating solution with at least a portion of the surface of an implant body and then drying it to form a coating layer.

[0077] Step (a) above is an immersion process to sufficiently disperse the decellularized tissue in a solvent, which can be performed at 20-40°C for 0.2-1.5 hours, preferably at 25°C for 1 hour, but is not limited thereto.

[0078] Step (b) above is a process of applying a coating solution to the surface of the manufactured implant body. Through this coating, decellularized tissue can be uniformly dispersed to ensure hydrophilicity and improve wettability with tissues within the human body. The advantage is that hydrophilicity can be imparted to the surface of the implant body through Step (b), thereby easily enhancing the biocompatibility of the implant.

[0079] The coating of step (b) above may be performed 1 to 10 times each. For example, the coating of step (b) above may be performed 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times. If the coating is not performed, the outer surface of the artificial implant is not hydrophilized, making it difficult to impart biocompatibility. If the coating is performed more than 10 times, the thickness of the coating becomes excessively thick, which worsens the tactile sensation of the implant, thereby lowering user satisfaction and increasing the likelihood of capsular contracture.

[0080] The coating of step (b) above can be performed by pre-treating the surface of the artificial implant body with a method such as ultrasonic cleaning and then dip-coating the coating solution of step (a), and can be performed using physical methods such as electrospinning or spray spinning, but is not limited thereto. When the coating is performed by the above coating method, a coating of approximately 1 mm can generally be formed on the surface of the artificial implant with a single coating.

[0081] After step (b) above, the method may further include step (c) cooling and freeze-drying the artificial implant. In this process, cooling may be performed using liquid nitrogen in step (c). This maintains a sterile state and facilitates subsequent freeze-drying.

[0082] Subsequently, by freeze-drying, the solvent remaining on the outer surface of the artificial implant is removed, thereby enhancing the integrity of the coating layer and further increasing the biocompatibility of the artificial implant.

[0083] The embodiments of this specification will be described in more detail below. However, the following experimental results represent only representative results among the above embodiments, and the scope and content of this specification should not be interpreted as being narrowed or limited by the embodiments. The respective effects of various embodiments of this specification not explicitly presented below will be described in detail in the relevant sections.

[0084] Example 1

[0085] First, an allogeneic dermal matrix was prepared as an acellular dermal matrix (ADM) and added to 80 parts by weight of sterile physiological saline as a solvent in the amount listed in Table 1 below, and hyaluronic acid was added as an additive in the amount listed in Table 1 below to prepare a coating solution. Then, the prepared silicone shell was immersed at 25°C for 1 hour. Afterward, the outer surface was washed, and the immersion process was repeated twice for a total of three coatings. Finally, the artificial implant with the outer surface coated was placed in liquid nitrogen to completely cool it, and then the solvent contained in the artificial implant was removed using a freeze dryer.

[0086] Comparative Example 1

[0087] The artificial implant was coated three times in the same manner as in Example 1, except that no cell-free tissue was added to the coating solution, and finally, the artificial implant with the outer surface coated was placed in liquid nitrogen to be completely cooled, and then the solvent contained in the artificial implant was removed using a freeze dryer.

[0088] Solvent (sterile physiological saline) (parts by weight) Allogeneic cell dermal tissue (ADM) (parts by weight) Hyaluronic acid (parts by weight) Example 180191

[0089] Experimental Example 1: Evaluation of the hydrophilicity of the outer surface of an artificial implant

[0090] The degree of hydrophilicity was measured for each artificial implant prepared in the examples and comparative examples using a contact angle analyzer under conditions of 37°C, which is the same as atmospheric pressure and body temperature.

[0091] First, three rectangular pieces were cut from the base (the posterior lateral part when implanted in the patient), the equator (the part with the largest diameter), and the apex (the anterior lateral part when implanted in the patient) of the outer surface of the artificial implant and placed on a plate. Then, 1 ml of distilled water was dropped onto the surface and left for 2 minutes, after which the contact angle was measured. This was repeated 5 times, and the average value of the results is shown in Table 2 and Figure 1 below.

[0092] Example 1 Comparative Example 1 Average contact angle (°) 49.67 1.1

[0093] Referring to Table 2 and Figure 1, it can be seen that in Example 1, the coating layer satisfies the acellular dermal tissue content range of the present invention, and the average contact angle is 60° or less, thus confirming that the outer surface of the manufactured artificial implant has excellent hydrophilicity. On the other hand, in the case of Comparative Example 1, although an additive was coated, the average contact angle was greater than 70°, indicating that hydrophilicity was not properly secured. Based on this high hydrophilicity, the experiment of Experimental Example 2 below was conducted to confirm that capsular contracture is suppressed when the artificial implant of the present invention is applied to an actual human body.

[0094] Experimental Example 2: Evaluation of the Inhibition of Spherical Contracture on the External Surface of an Artificial Implant

[0095] The responsiveness and biocompatibility of the cells were evaluated by culturing adipose tissue-derived stem cells on the surface of each artificial implant prepared in the examples and comparative examples.

[0096] Specifically, four artificial implants manufactured in the examples and comparative examples were prepared for each group, and after ethanol disinfection, they were inserted below the subcutaneous muscle layer (panniculus carnosus muscle) of pigs. After 8 weeks (2 months), the capsule and blood formed around the inserted implants were collected, and the following experiment was conducted.

[0097] To measure the concentration of interferon-γ, an inflammation-related cytokine, through immunohistochemistry (IHC) staining, blood samples were cultured for 16-24 hours, and the concentration of interferon gamma was measured using an enzyme-linked immunosorbent assay (ELISA). The results are shown in Figure 2 (a) below.

[0098] In addition, to confirm the in vivo inhibitory activity of spherical contracture, the collected capsules were stained with H&E (hematoxylin and eosin stain), and the thickness of the capsules was observed under a microscope. The thickness of each capsule was divided into three parts and measured three times for each part, and the results are shown in Figure 2 (b) below.

[0099] Here, interferon-γ (IFN-γ) is a type of cytokine, and its concentration is proportional to the likelihood of inflammation and the potential for the expression of anaplastic large cell lymphoma (ALCL). Referring to Figure 2 below, it was found that Example 1 satisfies the content range of the coating layer proposed in the present invention, and since the concentration of interferon-γ is maintained at a lower level compared to Comparative Example 1, the likelihood of ALCL expression is reduced, and the inflammatory response is also reduced. In addition, it was confirmed that the average thickness of the film formed in Example 1 is approximately 65 μm, which is significantly lower than that of Comparative Example 1, which shows an average film thickness of approximately 120 μm.

[0100] Therefore, since the above artificial implant utilizes acellular tissue such as ADM coated on the surface of the implant, it can suppress inflammatory reactions that may occur in the user upon implant insertion and further reduce the possibility of capsular contracture. As such, it is more biocompatible and user-friendly compared to conventional artificial implants, and thus can be used as a next-generation artificial implant.

[0101] The foregoing description of this specification is for illustrative purposes only, and those skilled in the art to which one aspect of this specification pertains will understand that other specific forms can be easily modified without altering the technical concept or essential features described in this specification. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single unit may be implemented in a distributed manner, and components described as distributed may likewise be implemented in a combined form.

[0102] The scope of this specification is defined by the claims set forth below, and all modifications or variations derived from the meaning and scope of the claims and equivalent concepts thereof should be interpreted as being included within the scope of this specification.

Claims

1. Implant body; and A coating layer formed on at least a portion of the surface of the above-mentioned implant body; comprising, The above coating layer comprises decellularized tissue, Artificial implants.

2. In Paragraph 1, The above-mentioned decellularized tissue is an artificial implant obtained by decellularizing muscle tissue, skin tissue, or fat tissue.

3. In Paragraph 1, The above coating layer further comprises an additive, an artificial implant.

4. In Paragraph 3, The above additive is an artificial implant comprising at least one or two or more selected from the group consisting of silicone elastomer, PCL (polycaprolactone), PLA (polylactic acid), PLCL (poly-lactide-co-ε-caprolactone), PLLA (poly-L-lactic acid), PGA (polyglycolic acid), PLGA (poly-co-glycolic-acid), PHA (polyhydroxyalkanoate), PDO (polydioxanone), hyaluronic acid, collagen, and gelatin.

5. In Paragraph 3, The above coating layer is an artificial implant having a content ratio of the additive to the decellularized tissue of 0.004 or more and 150 or less.

6. In Paragraph 1, An artificial implant having a coating layer thickness of 0.01mm to 10mm.

7. In Paragraph 1, An artificial implant having an external surface contact angle of 120° or less.

8. In Paragraph 1, The above-mentioned decellularized tissue comprises water, organic matter, and inorganic matter, and is an artificial implant comprising at least 30 parts by weight of the organic matter with respect to 100 parts by weight of the total of the organic matter and inorganic matter.

9. In Paragraph 8, An artificial implant, wherein the above organic material is at least one selected from the group consisting of collagen, elastin, proteoglycan, and laminin.

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