TW201200170A - Tissue repair device derived from fish scale - Google Patents

Abstract

The present invention discloses a tissue repair device derived from biodegradable and biocompatible fish scale comprising the favorable mechanical strength and the special microchannel structure which is good for cell attachment and proliferation. Before the tissue repair device is used for living body, for example human body, the content of the LAL value is less than 1000 Eu/ml, the best of LAL value is below 200 Eu/ml. In one embodiment of the invention, the LAL value for medical device is below 50 Eu/ml.

Description

201200170 VI. DESCRIPTION OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention is a biological structure, which is a tissue repair structure that takes care of a living body such as a human body. [Prior Art] Millions of people around the world suffer from eye diseases, some are congenital and some are caused by the day after tomorrow, such as chemical burns. For patients with corneal damage, mild medication can maintain normal vision; however, patients with severe corneal damage often need to be treated surgically. The traditional treatment method is to use cornea transplantation to restore the patient's vision, but the limited corneal source is a problem that needs to be solved. This factor also makes the research and development of corneal substitutes increasing. Due to the nature of the different materials, corneal substitutes were born using different principles. At present, synthetic polymers are used as the mainstream, and the use of core and skirt technology is used to restore the patient's vision to normal. For example, in U.S. Patent No. 6,976,997, poly-2-hydroxyethyl methacrylate (pHEMA) is used as the core portion of the crucible, and for the skirt portion, polytetrafluoroethylene is used. (polytetrafluoroethylene, PTFE) or expanded polytetrafluoroethylene (ePTFE) is used as a material for corneal repair. In addition, the core part also has artificial cornea made of polymethyl methacrylate (PMMA), such as Marshall G. Doane, et al., "Fabricati〇n〇fa Keratoprosthesis", C〇rnea' 15(2), 179-184 (1996). However, the above-mentioned polymer materials are not biodegradable materials, so they are continuously present in the patient's eyes after being implanted in the patient's eyes, provided that the material itself has insufficient oxygen permeability or excessive refractive index. If you continue to maintain a good state after planting a living object (such as a human body), it may still cause a burden on the patient's eyes. Therefore, the use of tissue engineering techniques as a method of corneal surgery provides a concept of another treatment. Tissue engineering technology provides a biocompatibility and biodegradable material as a scaffold to provide a three-dimensional structure of the three-dimensional space, allowing the patient's own cells to enter the struts; as time goes by, patients The cells themselves can grow well on the fulcrum, and the different components contained in the nucleus will gradually be turned over. (4) The scales are decomposed. After the ridges are completely decomposed, the patient's own enemy has grown up, but _ fine repair and the purpose of vision recovery, and this organization is the patient's own wealth, so there will be no immune rejection. ··· and other side effects, the prognosis is better. The conventional method of obtaining the scaffold material is to take the tissue directly from other species (or the same species) and perform appropriate steps such as decanting, and then use the tissue repair according to the actual requirements according to the characteristics of the material, such as U.S. Patent No. 201200170, No. 7, 678, 144, the small intestine submucosa (SIS) for vascular grafts; the decellularized renal capsule mentioned in U.S. Patent No. 70,708,899 (renai capsuie) An implant for use in a cardiac catheter stent and a decellularized amniotic membrane described in U.S. Patent No. 6,326,019 is used for corneal tissue repair. Because the strips produced in this way have their own mechanical strength, they are more suitable for the limitations required by human implants, and

The preparation procedure of the stent is relatively simple, and the stability of the stent process is relatively south compared with the synthetic polymer. However, the use of animal tissue as a scaffold for tissue engineering, if the animal and human being used have common infectious diseases, the safety of the use of the stent will be another issue that needs to be taken seriously. In view of this, how to improve the current problems of corneal repair materials, and to develop a simple and reliable safety and effectiveness of the weaving repair device is a goal that the relevant industry is committed to. SUMMARY OF THE INVENTION A novel purpose is to provide a tissue repair structure, particularly a tissue repair structure applied to the repair of damaged tissue of a body (such as a human body). This article contains a special micro-cavity (----attachment and additional i channel (rai) hanneu, 纟ur microcells of this new type of tissue restoration structure. In the organization repair 201200170 loss angle =: weaving =, - tissue repair structure, the other purpose of the test cortex type 2 is to provide a kind of tissue repair structure, applied to the dermis layer filled tissue repair structure. The purpose of the skin table is to provide - Tissue repair structure applied to the tissue repair structure of the skin wound dressing.

Another purpose is to provide a tissue repair structure for tissue repair structures that are produced after the prevention of suture marks. If type (four) - the purpose is to provide a kind of tissue repair structure, applied to the tissue repair structure of bone deficiency, such as bone nails, bone plates, etc. The new-provided _ repair structure contains - a substrate that has been treated with appropriate steps, biodegradability and biocompatibility of scales. Because the structure of the tissue repairing structure provided by the present invention is special, the new---the rhyme material can be converted according to the requirements of the _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ The strength of the tissue repair structure, and this processing step is relatively simple. The structure of the tissue repair described in the present invention can be further understood by the following detailed description and the accompanying drawings. [Embodiment] The tissue repairing device of the present invention mainly provides a tissue repairing structure of a living body (such as a human body) having sufficient mechanical strength, which is washed by a fish scale, and only a part of the fish scale is retained as a tissue repairing structure, and Before use, the tissue repair structure must be washed to UL.

ESI 7 201200170 amebocyte lysate ' LAL test), which is a test method for analyzing the content of endotoxin contained in bacteria', and the test value of the treated tissue repair structure in the LAL setting must be less than 1 class Eu/nd, which is preferably implemented. For example, the LAL test value is less than 200 Eu/ml. Wherein the processing steps of the tissue repair structure can be processed according to the actual application situation, at least the steps of removing cells, decalcifying, etc., and the tissue repairing structure, especially the fish scales from the bony fish, wherein Round scales and scales. Referring to Figures 4 and 5', 'Fig. 4 shows a scanning electron microscopy (SEM) image of the fish scale microstructure; and Figure 5 shows the corneal cell culture taken from the rabbit's eye. A scanning electron microscopy (SEM) image of the growth of corneal cells after fish scales on fish scale materials. The microstructure of the surface of the scale has a special microchannel portion, and the width of the microchannel is at least 1 μm. In a preferred embodiment, the microchannel is microchannel. The width is 10_50 eggs, and the height of the microchannels is at least 1 em'. In a preferred embodiment, the height of the microchannels is 1-30, please refer to FIG. 4A. With this special microchannel microstructure, it will facilitate the cell's protrusion along the microchannel above the fish scale material treated by appropriate steps (such as decellularization, decalcification, etc.). The wall (ie, the cells will be attached and propagated along the direction of the arrow) will be referred to Figure 5A. The so-called microchannel microstructure refers to the surface morphology observed under scanning electron microscopy (SEM), and the so-called microchannel (micr〇channei) The width refers to the distance between the raised wall and the wall, please refer to the arrow in Figure 4A; as for the micro-channel Cmicnxhannel) the height refers to the height of the raised wall. Another feature of the scale structure is that its surface topography is a concentric circle of radiation radiating from the center. This surface topography will help guide cell growth, see Figure 4B and Figure 5A.

As for the material of the fish scale, after the treatment of the process of the withdrawal, etc., the extracellular matrix (ECM) structure of the #scale itself is not damaged, so the fish scale material having the extracellular matrix will not only Conducive to the cell's _ money proliferation, but also because its structure is not destroyed by the process of the process, but to maintain its original three-dimensional (3-D) structure, which is conducive to the cell without losing its type and function The lower 'stable presence continues and persists in the decalcified scale structure, please refer to FIG. 4C and FIG. 5B and FIG. 5C. In addition, the past literature pointed out that the internal structure of the fish scale is a plurality of county structures composed of a layered structure and the structure of each layer is transported, and the complement is arranged in a forward direction. Furthermore, the adjacent layers and the layers of the directional fiber structure are approximately 90 degrees out of phase. Forming - staggered secret filling structure. Therefore, the fibrous structure of the staggered layers of the fish scale provides good mechanical properties and can also be maintained in a living organism (such as the human body) (10) - sufficient mechanical strength to provide a stable stent, allowing the cells to grow. . In addition, depending on the application, the (four) process can be used to create a suitable mechanical strength for cell growth in 201200170 implanted organisms (such as humans). The fibrous structure in the layered structure of the fish scale is collagen. The collagen is mainly composed of collagen type (Ι), so it is also used for tissue repair and prevention of scarring. Have positive help. In addition, many tissues in an organism (such as a human body), especially human bodies, such as the cornea, skin, bones, etc., one of the main components of the extracellular matrix is collagen type (collagen type). -I), so the main components of the scales are exactly in line with the application of tissue repair in living organisms (such as humans). Furthermore, there is also a calcium phosphate miscellaneous molecule between the fibrous collagen (c〇l lagen) structure of the fish scale, such as hydrQxyapatite (HAP), tricalcium ph〇sphate (Tcp)... And the inclusions in which they are closely bonded to each other, forming a particularly perfect interlaced structure, thus providing a good tensile strength of at least 〇·5 MPa, wherein the preferred embodiment is 〇·5 50 MPa, if it is to be treated When used in tissue engineering stents, the fish scales provide sufficient mechanical strength to be implanted in an organism (such as a human body) and do not disintegrate the stent and lose its function. The fish scale itself has good mechanical properties and similar biological (such as human body) components, and thus is a good biological biomimetic material. In addition, until now, the fish-brewed humans have a common spread. Therefore, when the fish scales are in contact with the human body or in contact with the body surface, the doubts about the possible infectious diseases of the human body can be excluded. 201200170 The scale-derived tissue repair structure can be used to prepare the material type in different ways depending on the application level. Please refer to Figure 1, which describes the tubular structure of the tissue repair structure; Figure 2 depicts the tissue repair structure of the plate form and the tissue repair structure of the powder form depicted in Figure 3, wherein the tubular form or flat form (piate form) The material of the form can be obtained according to the use of the special mold to obtain a specific shape. Alternatively, it may be a screw form tissue repair structure, the details of which are described in the various embodiments below. Example 1 Preparation of decellularized fish scales After obtaining about two hundred grams of fish scales, 'wash at least three times with twice deionized water until clean. The step of decellularization is then carried out in the cleaned fish scales, wherein the decellularization step can employ hypotonic, detergent, Triton X-100, sodium dodecyl group using low osmotic pressure to cause cell swelling. Sodium sulfate (SDS), protein inhibitor, DNase, and ribose nucleus (Mase), followed by methods to increase porosity and porosity Then Xiang. The fish scales mixed with the above steps. After the treatment, the material is rinsed with sterile phosphate buffer at least three times and then immersed in phosphate buffer, which is the decellularized fish scale. m 11 201200170 Example 2 Preparation of decalcified fish scales At room temperature, the fish scales were placed in a 5% nitric acid solution for 6-16 hours to reduce inorganic components such as calcium phosphate salts inside the scales, such as hydroxyl apatite. Hydrate (hydroxyapatite, HAP), tricalcium phosphate (TCP), etc. Then, after immersing the above materials in A solution (10% EDTA, 2% nitric acid) for 2 to 3 days at 4 ° C and continuously changing the a solution, the above materials will be more gradually increased with the soaking time. Further, the inorganic components such as calcium phosphate salts in the fish scale are reduced, such as hydroxyapatite (HAP), tricalcium phosphate (TCP), and the like. The material treated in the above procedure was immersed in 7% alcohol and stored in 4<> Example 3 Measurement of Oxygen Permeability of Descaled Fish Scales After oxygenation (Dk) of decellularized and decalcified scales, an oxygen permeability meter (Oxygen Permeometer M〇del 2〇1T; Heart., Albany, CA' USA) In the environment of absolute humidity and temperature evil, the oxygen permeability of the material is determined by the value of the Gu Lin test towel as a X 1 〇 (cm2 X ml 〇 2) / (sec χ ml χ 咖 %), wherein the oxygen permeable rate of the tissue repair structure is preferably 3G to 13G W χ W 〇 2) / (sec X ml x mmHg). 12 201200170 Embodiment 4 In an embodiment, the structure of the fish scale tissue repaired by the above partial or all steps can be used as a scaffold material in tissue engineering and applied to damage of an organism (such as a human body). Repair of the cornea. The decalcified fish scales are cut to the appropriate size' size to fit the size of the patient's lesion, typically 4-20 mm in size. Before implanting an organism (such as a human body), the tissue repair structure must be washed to a level of LAL (1 imuius amebocyte lysate, LAL test), which is a method for analyzing the content of endotoxin contained in bacteria, and washing The net tissue repair structure must have a test value of less than 1000 Eu/ml in the LAL assay and a preferred embodiment LAL test value of less than 2 (10) Eu/ml. In one embodiment, the corneal cells are removed from the rabbit and placed in the fish scale tissue repair structure treated by the aforementioned partial or all steps, and the first, second, and third are respectively observed by a confocal microscopy microscope. Seven days of corneal cell attachment and proliferative behavior. Before observation, 'in order to be able to observe the cell attachment pattern on the tissue repair structure', it is necessary to first fix the cells on the tissue repair structure without destroying the cell type. In one embodiment, the selected cells are decanted to a 3 7% fQnnaidehyde (pentane-path) reaction for 15 minutes at room temperature. This can be used to provide the same function of chemical reagents to achieve this purpose, such as formic acid (formaldehyde) ° 201200170 Then, in order to enable the dye to smoothly enter the cell surface to reach the desired site, it is necessary A hole is created in the cell membrane. In this embodiment, the chemical agent selected to achieve the perforation is Trit〇n χ_1〇〇, and the reaction is for five minutes. In order to reduce the non-specific combination, in this case, 10% normal g serum (normal g〇at serum) and 5% bovine serum albumin (bovine serum albumin) were used for one hour at room temperature. The step of blocking is performed. In order to observe the eon eal 显微镜 显微镜 于 于 于 于 于 eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon eon -phalloidin was used to stain F-actin (F_actin), and the results are shown in Fig. 6. Please refer to Figures 6A, 6B, 6C and 6D. In the figure, the red glory is the F-aetln that has been dyed, and the green fluorescent light is the part that is stained to the nucleus. The fish riding structure does have a patchwork extension and hyperplasia, and as the accompanying time increases, the number of cells on the scale material that has been treated in an appropriate step increases. In the fifth embodiment, in the embodiment, the fish scale processed by the partial or all steps may be applied to the external wound treatment of the bird (four), and the external wound may be the wound left by the suture after the operation. The trauma caused by Qing light...etc., using the above-mentioned partial step and full treatment, as a wound dressing 201200170, not only can effectively isolate the infection of external wounds. In addition, the fish scale is composed of collagen. The collagen (c〇iiagen) referred to is mainly collagen type-1, and this main component of the fish scale is just like the collagen in the skin. The protein has the same composition, so it can also prevent the wound from being unsightly due to the scars left by the sore. More importantly, the special structure of the fish scale provides a sufficient tensile strength of at least 〇·5 MPa during the wound sore process. Prior to use, the tissue repair structure must be washed until it can be identified by LAL (limus amebocyte lysate, LAL test), which is a method for analyzing the content of endotoxin contained in bacteria, and the tissue repair structure after washing is The test value in the LAL identification must be less than 1 〇〇〇 Eu / ml, and the preferred embodiment has a LAL test value of less than 2 〇〇 Eu / mi. Embodiment 6

In the implementation of the wealth, the fish scales of the former step by step by step can be used to protect and repair the damaged parts of the eye, such as sclera lenses (scierai le le), contact lens system (c〇ntact small eyes) Intraocular lenses and corneal bandage lenses (6) axis bandage lenses)···etc. After the eye surgery, the lens is worn, the laser protection layer is worn after the laser surgery or the needle glasses are worn. The damage caused by the ship, etc., can be _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Produce ·.· and other uses. However, the use of the 201200170 fish scale is not limited to the use of all scales as a covering for the eyes, and may be combined with other materials used for contact lenses to retain the central main visual area; only the scales are placed outside the central visual area. To prevent the creation of other unnecessary problems. Before use, the tissue repair structure must be washed until it can be identified (limulus amebocyte lysate, LAL 忉 pair), which is a method for analyzing the endotoxin containing bacteria in the bacteria, * washed and woven fabric repair structure The test value in the LAL identification must be less than 1 〇〇〇 Eu / ml, and the LAL test value of the preferred embodiment is less than 2 〇〇 Eu / π α. Embodiment 7 The fish scale processed by the foregoing partial steps or all steps may be applied to the soft-defective implant material, such as the face inspection, the fishtail pattern, and the like. When the material injected subcutaneously is formulated into a liquid state, the characteristics of the solution must have a weight characteristic. For example, if the material has a certain axis, the machine will be expanded immediately after she has weaved it. Because it is not enough, it cannot be used as a function of the fixed structure. Generally speaking, the part (4) or the total suppression When the scales of the treated fish scales are formulated into a solution, the viscosity is measured by a capillary rheometer, preferably 2 〇 2 berth ( ―, and the maximum is not more than the surface poise (p〇ise) is ^== _ Steps or all the steps processed by the whole fish, the bamboo shoots, the shame of the material or the p-step processed fish scales must first be ground through the grinding equipment to the size suitable for thin 201200170

The purpose of use by needle injection. In addition, it is worth noting that before implanting an organism (such as a human body), the tissue repair structure must be washed to pass the limulus amebocyte lysate (LAL test), which is an analysis of the endotoxin contained in the bacteria. The test method of the content, and the tissue repair structure after washing must have a test value of less than 1 〇〇〇Eu/ml in the LAL identification, and the LAL test value of the preferred embodiment is less than 2 〇〇Eu/ml. • Embodiment 8 In one embodiment, the fish scales treated in the foregoing partial or all steps may also be used in the application of bone patches, such as bone nails, bone plates or bone fillers. And the shape of the nail is a screw-like structure of a screw f〇rm. Several key factors for bone patching are that the implant must have sufficient mechanical strength and stiffness to accommodate the strength of the bone, avoiding stress concentrations due to large differences in mechanical strength, resulting in damage to the implant or the patient's own bone. In addition, whether the implant can induce the growth of osteoblasts also plays a very important role. If the implant itself does not facilitate the tissue regeneration of the patient, it will be difficult to fully recover the damaged part of the patient. Therefore, a better bone patch [such as bone nails, bone plates. The fish scales are prepared by cold, east compressed extrusion manufacturing (FCDM) or hot extrusion layer forming (compressed deposit manufacturing, HCDM), and can be used for the preparation of bone patches. Different shapes are used in conjunction with different molds

ESI 201200170 The nails and bone plates are designed to meet the needs of the patient's damaged area. The advantage of using fish scales for bone replenishment is that the silk itself contains squamous protein ((7) u η), calcium salts (such as hydroxyapatite (hyd (7) lamp, HA, HA?), tank acid (tricalcium Phosphate, TCP), etc.) The components of the bones (such as the human body), so the process will be more convenient. In addition, ...,%, the excellent mechanical strength of the body will also provide a good machine strength after the preparation process such as the freeze extrusion lamination molding method or the addition of two extrusion lamination molding methods. The charm of the ornament is strong. And the county egg self (gq 丨丨 difficult print) T induced the production of osteoblasts, so as the patient's own osteoblasts gradually regenerate in the damaged / sputum, forming a sound tissue; at this time, plant The bone nails and bone plates formed by the fish have also been gradually solved by specific enzymes in the body over time. Therefore, after the patient's tissue growth is good, the implant is not required to be removed by the second operation, which can reduce the risk of surgical infection and reduce the patient's discomfort after the operation. It is worth noting that before implanting an organism (such as a human body), the tissue repair structure must be washed to a UL identification (limulus ameb〇cyte lysate, LAL test), which is an analysis of the endotoxin contained in the bacteria. The test method of the content 'the tissue repair structure after washing must have a test value of less than 1000 Eu/ml in the LAL identification, and the LAL test value of the preferred embodiment is less than 2〇〇Eu/ral °. In the actual example, the tissue repair structure of the scales processed in some or all of the steps can also enhance the mechanical strength and stability of the tissue repair structure by using a physical cross-linking agent. Here, the physical crosslinking agent 201200170 refers to a method of crosslinking by ultraviolet light (UV light), heat, or the like. If heating is used for cross-linking, the heating temperature should not exceed 15 〇 QC to avoid the destruction of biomolecules by the temperature. [Generally, the preferred implementation temperature is 70-140 °C. Embodiment 10 In one embodiment, the tissue repair structure of the fish scale treated by the foregoing partial or all steps can also be used to enhance the mechanical strength and stability of the tissue repair structure by chemical use. The chemical crosslinking agent referred to therein may be selected from the group consisting of glutaraldehyde, carb〇diimide, aminosilane, genipin, and hexadecenyl diiso. Hexamethylene diisocyanate (HMDI), formaldehyde (formaldehyde), acyi azide, etc. Of course, it is also possible to use other equivalent chemical intersections to tailor the purpose. In the preferred embodiment, the amount of the chemical cross-linking agent can be selected as the suffix, and the pentane _ is preferably used at a concentration of about 〇. _~3· _. In another preferred embodiment, the chemical cross-linking agent used may be selected from the group consisting of (3-dimethylaminopropyl) 3-ethylcarbodiimide hydrochloride (1 ethyb 3-(3-dimethylaminQpropyl). -carbodiiinide hydiOchlodde' EDC) (a compound of carbodiimide) and used at a concentration of about 1 to 300 mM. Although the present invention has been described above by way of a preferred example, it is not intended to limit the present invention. For example, Lin's departure from the spirit and scope of this new (4) should be included in the scope of the following patent application. 0 201200170 [Simple description of the diagram] Figure 1 is a circular column of the new tissue repair structure (her uiar f〇 Schematic diagram of rR 〇form. Figure 2 is a schematic diagram of the plate f〇rm type of the new tissue repair structure. Fig. 3 is a powder form of the novel tissue repair structure (p〇wder type diagram) Figure 4A shows the scanning electron microscopy (SEM) image of the scale structure of the fish scale treated with appropriate steps (35X). Figure 4B shows the scanning electrons of the fish scale structure treated by appropriate steps. Scanning electron microscopy (SEM) image (600X). Figure 4C is a scanning electron microscopy (SEM) image of the internal fiber structure of fish scales treated with appropriate steps. Figure 5A shows rabbit cornea. A scanning electron microscopy (SEM) image of the fish scale material treated in an appropriate step (culture time: 1 day). Scanning electron microscopy (SEM) image of cultured rabbit corneal cells in a properly processed fish scale material (culture time: 2 days) [s] 20 201200170 Figure 5C shows rabbit corneal cell culture in the Ele 电子 micro micro micro micro micro micro micro ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele ele 第 第 第 第 第 第 第 第 第Focus microscope (c〇nf〇cal micr〇sc〇py) dark field fluorescence map (culture time: 1 day). Figure 6B shows rabbit horned owl cells cultured in appropriately processed fish" • A co-focus microscope (c〇nf〇cal micr〇sc〇) dark field fluorescence map of the 粦 material (culture time: 2 days). Figure 6C shows rabbit corneal cell culture in a proper step A total light-focus microscope (c〇nf〇cal micr〇sc〇py) dark field fluorescence map of the fish scale material (culture time: 3 days). Figure 6D shows rabbit corneal cell culture in appropriate steps Processed fish scales A total light-focus microscope (c〇nf〇cal micr〇sc〇py) dark field fluorescence map (culture time: 7 days). [Main component symbol description] Tube form Tissue repair structure ^ Microchannel microstructure of a tissue-repaired structure in a tubular form 11 Plate-like tissue repair structure 2 Plate-like tissue repair Internal microchannel microstructure of the structure 21 [S3 21 201200170 Powder-like tissue repair structure 3 Powder-like tissue repair structure of internal micro-channels (mi crochanne 1) Microstructure 31

[s] 22

Claims (1)

201200170 VII. Patent application scope: 1. - The tissue repair structure contains at least one fish scale with a microenK±annei structure. 2. The tissue repair structure of claim 1, wherein the fish scale having a microchannel structure is derived from a bony fish, wherein the fish scale of the bony fish can be selected from a round scale or a scale. 3. The tissue repair structure as claimed in claim i, wherein the fish scale having the micr〇 channel structure has a LAL value of less than 1000 Eu/ml. 4. The tissue repair structure according to claim i, wherein the fish scale structure having a microchannel structure is fibrous. 5. The tissue repair structure of claim i, wherein the fish scale having a microchannel structure contains collagen (c〇n print). 6. The tissue repair structure of claim 1, wherein the fish scale having a microporous Onicrochannel structure further comprises squaric acid contacts. 7. The tissue repair structure according to claim 1, wherein the fish scale having the microporous C Onicrochannel), .D structure has a fibrous multi-layer structure interlaced with the layers. 8. The tissue repair structure of claim 19, wherein the fish scale having a microchannel (Wh fine el) structure is a circular tube column (she (6) -). 9. If you apply for the patent scope! The tissue repair structure according to the item wherein the fish scale having the microporous Onicroch fine el) has a flat shape (piate f-cut). 10. The tissue repair structure of claim i, wherein the fish scale having a micro [S1 23 201200170 microchannel structure is a powder form. 11. The tissue repair structure of claim 1, wherein the fish scale having a microchannel structure is a screw form. [s] 24