TWI323665B - - Google Patents

Description

1323665 IX. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention relates to a biomedical material, and more particularly to a biomedical material that can be applied to promote wound healing. The biomedical materials of the present invention have the functions of stopping bleeding, promoting tissue regeneration, and promoting nerve repair and regeneration. [Prior Art]

The skin is the largest organ in the human body, and its total surface area contract is 1.5 to 2 square meters. The skin generally has the function of regulating body temperature and regulating water to avoid dehydration, and is also the primary line of defense against foreign pathogens. When the skin is injured, it may cause imbalance in body function, severe organ imbalance, and even death. Inflammation, ulcers, trauma, burns, surgery, and congenital malformations cause skin defects and abnormalities, which not only cause physical pain to the patient, but also often cause trauma to the patient at every stage of treatment. In the process of wound repair, an ideal environment is needed to accelerate the healing of the wound. Normally, normal people can usually heal a small area of the wound themselves. However, for a large area of burned patients, the skin of the patient's own body is usually cut to a thickness of about 0.014 inches, and the machine is opened _2 times. Covered in the injured area, also known as the splitthickness skin autograft. However, patients with large areas of injury have limited skin left alone, or when the patient's ability to regenerate wounds is weak, such as digging the eastern spleen to supplement the Western Wall in this way, it is no different. In patients with deep wounds and poor skin healing ability, such as ulceration of limbs in diabetic patients, in addition to using anti-inhibition to prevent infection, it is usually necessary to use allogeneic skin grafts. 5 In the source of xenogeneic skin, since 1500, some people have tried to make the skin of the skin of all skins as a source of allogeneic skin transplantation. In 1692, some people used the expanse month, in 1906, the rabbit skin, in 1966, the dog's skin, 1965. From now to now, there are scientists _ continued to make secrets, as a material for xenogeneic skin transplantation. The advantage of xenogeneic skin grafting is that its source is not scarce, and the inner layer of the skin is biocompatible collagen; however, its disadvantages are: (1) different, transplanted skin needs to be treated in a specific way to remove animal skin. The substance, (2) the animal-derived skin may carry a protein virus, and (3) the treated animal's skin is unable to obtain blood from the wound, often falling off. The most commonly used wound treatment for general burns is synthetic dressing, because it is simple to manufacture and obtain materials. Synthetic _ permeate can be attached to the wound. ‘There is elasticity, and it allows the wound fluid to flow out and avoid bacterial infection, so it has the most products on the market. Most of the materials used in synthetic dressings are polyester and polyamino? Acid _ film), polymorphic (p〇lypeptide) or chemically synthesized polymers (such as nylon) are mainly non-biodegradable materials. It is covered with silicone rubber and the inner layer contains antibiotics. It is suitable for superficial wounds. The healing time of wounds varies from 7 to 15 days. After wound healing, it can be removed. In recent years, 'the international application of tissue engineering methods to develop wound dressing technology has made rapid progress, but it is still limited to the epidermal tissue and connective tissue of the skin, and the artificial skin of the dog is not used. The preparation process is long, the method is tedious, and the price is also It's not cheap. It usually takes 1_2 months to heal the wound, and it can't meet the needs of patients with various skin defects. Therefore, 'the wound dressing itself still has a lot of room for improvement, including increasing its adhesion to the injury σ, preventing bacterial invasion and growth, increasing elasticity and extensibility, increasing preservation, non-rejection and foreign body reaction, water. Gas can be expected, internal hearing can be fine (four) shift, (4) bio-decomposable material f, biocompatible, non-toxic, easy to store, reduce the occurrence of sputum scars, shorten wound healing time and reduce prices. In addition, Bai Zhi plays an important role in the regeneration of the surrounding objects, the degree of cell migration and sorting, and the regeneration of the surrounding gods and workers. Therefore, providing a biomedical material that facilitates cell migration and sequencing will help repair nerve cells. SUMMARY OF THE INVENTION The purpose of the present invention is to provide a biomedical material for tissue engineering, which has anti-free radical anti-oxidation, reduces inflammatory reaction, and reduces immune response, in addition to having good biological phase and non-toxicity. It reduces the reaction of foreign substances, accelerates blood coagulation (hemostasis), has antibacterial properties, and accelerates the growth of regenerative cells on biomedical materials and promotes matrix secretion. In addition, the biomedical materials of the present invention can also accelerate the wound healing by increasing the speed at which cells migrate, sort, and regenerate, thereby achieving cell sorting. In addition, the biomedical materials of the present invention can also be used to promote regeneration of nerve tissue. A biomedical material according to the present invention comprising: - a matrix based on a polymer material selected from the group consisting of chitosan, collagen, polyester and polyamine a group of formates; a plurality of nanoparticles dispersed in the matrix, a) wherein the nanobes account for 嶋~5% of the total amount of the biomedical material and are indicated in accordance with the present invention A biomedical material for tissue engineering, which has the biocompatible 'biodegradable' required for biomedical materials. It also has an inflammatory reaction that accelerates blood coagulation, anti-free radicals, and anti-oxidation to reduce injury σ. The immune response reduces the antibacterial activity of the foreign body and can accelerate the growth of the regenerative cells on the biomedical material and the secretion of the matrix. In addition, the biomedical materials of the present invention can increase the speed of cell migration, sorting and regeneration in order to increase cell regeneration, and achieve the purpose of healing the scars by sorting into cell tissue. In addition, the biomedical materials of the present invention can also be used to promote regeneration of nerve cells. The present invention will be further described by the following detailed description and examples. These two examples are not intended to limit the disclosure of the present invention. Those skilled in the art will be able to make some modifications and (4) without departing from the scope of the invention. [Embodiment] A biomedical material according to the present invention is composed of a 1-molecular material-based matrix and a nanoparticle which is reduced in the matrix. It can be applied to the present invention as an example of the polymer material, such as Chit〇San, collagen, polystyrene, polyamine citrate, or

> Kun compound. When chitosan is used as the butyl sulphate in the present invention, in the case of Yu Shizheng knives, the limitation of the formula can be applied according to the conventional formula: Batongye has the following formula (I)

(I) =, a chitinase which can be applied to the present invention, for example, can be prepared by using a chitosan compound. According to f, it usually has the structural formula shown by the following formula (π): ^Tf's meaning, its , · ch2oh

CH2〇H

(Π) The chitosan can be self-existing in the exoskeleton of the arthropods. Therefore, when the chitin is not completely gone (10), it is a mixture of a few diced and a few diced. The ratio of the second: is generally determined by the deacetylation process of chitosan. The chitosan which can be applied to the present invention is preferably not less than, and more preferably Good is not less than 75%. 9 is known as a high molecular polymer, which usually has a molecular weight of tens of thousands of Dalton (Da), and the molecular f of chitosan applicable in the present invention is in the present invention. There is no particular limitation, but it is preferably 10 to 1,500 kilotons (kDa), more preferably lake ~], _ thousand daltons (kDa). Then, the butyrin can be obtained by the external bone path of the arthropod, by the conventional chemical processing method, or can be obtained from the cell wall of the plant, the _ and the true _ by a conventional treatment method. Traditionally, it has good antibacterial, biocompatibility, bioactivity and biodegradability. On the other hand, the degradation rate in the regenerated objects is slow, and the higher the degree of degeneration, the slower the riding. Furthermore, the product degraded by chitosan is glucosamine, which is not cytotoxic. The biomedical material prepared by using chitosan as a substrate will have the advantage of knowing 4 chitosan. Further, the above-mentioned collagen which can be applied to the present invention is not particularly limited, and for example, a diterpene purified from beef tendon can be used. . _ phantom or purified from the second type of porcine cartilage: (yp collagen), but not limited to this. In the present invention, there is no particular limitation in the present invention. The particle size of the nanoparticle described above is preferably a chopped strand, and more preferably, it can be applied to the nanoparticle of the present invention, which may be a gold U particle or a non-metallic nep. Examples of the metal nanoparticle described above are, for example, gold nanoparticles (nano gold), silver nanoparticles (nano silver), and the like, but are not limited thereto. As an example of the aforementioned non-metallic nanoparticle, for example, a seed of i02, a clay, a ceramic, or the like, but not limited thereto. The proportion of the aforementioned nanoparticle relative to the total weight of the biomedical material is preferably 0.0005. /. ~5% (w/w), more preferably 〇〇〇1~〇〇1% (▲) (ie 10~100ppm). The material of the present invention may be non-porous and may be fibrous; the surface of the medical material is a smooth surface or a surface having a micro-groove structure. The preparation method of the above-mentioned biomedical material can be prepared by mixing a polymer solution with nevraz. For example, in the case of chitosan, it can be prepared by dissolving chitosan in a water-soluble solution. The picker 'adds the nanoparticle to the above-mentioned chitin-rich solution, and evenly distributes the =^ to the aqueous solution. Finally, several T (four) cut (four) rows containing the nanoparticles are dried, # the invention of the biomedical material. < The aforementioned weakly acidic aqueous solution preferably means water having a pH of from 3.5 to 6.5 = more preferably an aqueous solution having a pH of from 4 to 6. The weakly acidic aqueous solution can be used as a 丨 乂. There is no particular limitation in the present invention. In the middle, the 1 m particle * is uniformly dispersed in the aqueous solution of chitosan, and / can be achieved by a stirring operation. The method of drying an aqueous solution of chitosan containing nano particles can be dried by freeze-drying at a normal temperature. According to the biomedical materials pointed out by the present invention, and the biocompatibility and non-toxicity:: has an accelerated blood and can accelerate the regeneration of fine, secondary anti-free radical, anti-oxidation, reduce the inflammatory reaction of π, reduce the & Reacts, reduces foreign matter reaction, and has antibacterial properties

2 growth and matrix secretion on biomedical materials. In addition, it is still possible to increase the speed of migration, sorting and regeneration on the material of the fine-grained material 4, thereby achieving a fine and woven sorting* achievement. Rapid injury σ healing. In addition, the biomedical materials of the present invention also have a better hydrophilicity than chitosan for promoting the rejuvenation of the god 35 cells. In addition, Example 1 Preparation of the biomedical material of the present invention

Weigh 5 grams of chitosan (molecular weight 4 〇〇 kDa, deacetylation degree 85 / ί), Fluka, Switerland) into 500 ml of 1% aqueous acetic acid solution, and stir until completely dissolved, by means of A 1% aqueous solution of chitosan was prepared. Take the original >50 ppm nano gold solution (average particle size 5~10 _ 'Jinghuatang), dilute it to 40, 30, 20 ppm with secondary water and take 5mI 'with 5 ml above Mix 1% aqueous solution of chitosan. In order to obtain a chitosan-Au solution. Similarly, a 500 mg nano silver solution (average particle size 5~1〇nm, Jinghuatang) was diluted with secondary water to 200, 40, 20 ppm 12 1323665 and then taken 5ml ' 5 mi of the above 1% aqueous solution of chitosan was mixed. To obtain a solution of chitosan-silver (chit〇san-Ag). The above chitosan-Au solution was applied to a slide having a diameter of 5 cm (thickness of about 10 μm) and allowed to dry at room temperature. After it is completely dried, it can obtain a chitosan-Au film.

200 μl of the aforementioned chit〇san_Ag solution was applied to a slide of a diameter of 3 2 (thickness of about 10 μm) and allowed to dry at room temperature. After it is completely dried, it can obtain a chit〇san-Ag film. Further, in the same manner as in the foregoing method, but without adding nanoparticles, a film was directly formed from chitosan, whereby it was used as a control group. Example 2 The surface morphology of the chitosan-Au film and the chit〇san_Ag film prepared in Example 1 was observed using an atomic force microscope (AFM). Atomic force

The operating conditions of the microscope were tapping mode (tapping m〇de)' scanning range was Ιμιη, 5 μιη, and the resolution was 1 nm. The probe material is Shi Xi (8), and the probe specifications are: SI-DF2〇 (f=l33kHz, (4) running). The roughness Ra(nm) of the surface of the film was measured and shown in Table-. Further, in Table 1, it can be seen that the chitosan film to which nano-gold and nano-silver are added has an average crude longitude of 3 to 5 nm and 4 to 5 nm. In addition, the phase diagram (phage) of the surface of the film can be observed by atomic force microscopy (refer to the first figure, whether nano gold or nano silver can be uniformly dispersed in chitosan to form a nanocomposite, And it can be seen from the first figure that nanocrystalline crystal grains (10 to 50 nm) appear in the nano composite material. "13 In the third embodiment, the films prepared in the respective examples were respectively cut into a diameter of 1.5 cm. The pattern is as follows: After the second water is dropped on the film to balance the water absorption, the excess moisture on the surface of the material is dried, and the contact angle of the surface of the material is measured using a contact angle meter (CA-D, Face, Japan). The measured results are shown in Table 2. The size of the conventional contact angle represents the hydrophilicity of the substance and the water droplets. The higher the contact angle, the higher the hydrophobicity, and the smaller the hetero-angle, the higher the hydrophilicity. As can be seen from the results, chitosan containing nanoparticle (nanogold or nanosilver) has a lower contact angle than the film of the control group. Therefore, the present invention can be known Biomedical materials are better than conventional chitosan Water-based. Example 4 The phase of the chit〇san-Au film prepared in Example 1 was observed by a phase contrast microscope (phase optical microscope). The results obtained are shown in the second figure. Microcrystallization of the surface of the glycan can promote coagulation (A.

Hoekstra et al., 1998, 19, 1467·71). From the second figure, it can be found that many tiny crystal regions appear on the surface of the experimental group, while the experimental group does not. This shows that the biomedical material of the present invention can promote blood coagulation and thereby achieve the effect of helping the wound to stop bleeding. 1323665 Example 5 The film prepared in Example 1 was placed in a well of a 24-well culture dish, and a glass cover glass was used as a control group. Human gingival fibroblasts (hGF) or human dermal fibroblasts (hSF) with a cell density of 5xl〇4 cells/ml were plated in each well, and imi cell solution was added to each well at 37 ° C, 5 Incubate in a cell culture incubator with % C〇2. After 96 hours of cultivation, the film was dried by freeze drying. Add 1.5 to the dried film, respectively.

Decomposing solution (containing 55 mM sodium citrate, 150 mM sodium chloride, 5 mlvi cysteine-HCl, 5 mM Na2EDTA, 1 mg of papain per 2 μl before use), placed at 6 〇t : The reaction was carried out for 24 hours (sample). The cell liquid was adjusted to six concentration gradients using the aforementioned decomposition liquid as a standard. Remove 0.5 ml of sample and standard, add 5 ml of fluorescent dye (containing 10 mM Tris-HCl, 1 mM Na2EDTA, 0.1 mM gasification sodium, adjust pH=7.4; add dye Hoechst 33258 (Sigma) before use. Slow

In the scouring solution, the concentration of the dye after dilution was 0.1 jug/ml), and the mixture was evenly allowed to stand for 1 hour in the dark. Absorbance values (Em: 458 nm, Ex: 365 nm) were measured using a fluorophotometer (F2500, Hitachi); a calibration curve was prepared using a standard product, and the number of sample cells was quantified using this calibration curve. The calculated results are shown in Table - II. 细胞 The number of cells obtained from the DNA analysis data of Table 3 shows that the experimental group has a larger number of cells. Further, a solution of chondrotin sulfate C sodium salt (Sigma) was prepared as a standard mouth using the above-mentioned decomposition liquid as a solvent. Take 0.5 ml of the sample and standard treated with the above decomposition solution, add 5 plus 15 DMMB dye (take 21 mg Dmmb dye (Aldrich) & 2 g sodium formate (Showa), dissolve in 5 ml 95% alcohol, After diluting with 800 ml of secondary water, adjust the pH to 1.5 with lanthanum (Fluka), adjust the final total volume to 丨L), and mix well. The absorption value (wavelength: 525 nm) was measured by visible light/ultraviolet spectrometer, and the calibration curve was drawn by the standard product. Then the calibration curve was used to determine the glycosaminoglycan (GAG) content in the sample σσ. . The calculated results are shown in Table 4. The results obtained in Table 4 show that the experimental group has more GAG amount. Separately, 0.5 ml of the sample treated with the above-mentioned decomposing liquid was taken, and an equivalent amount of 6N hydrochloric acid was added thereto, and the reaction was carried out at ll ° C for 24 hours. The sample after the acidification reaction described above is subjected to vacuum drying to remove the solvent, and then 10 (1) water is added to the dried sample to dissolve the sample. Hydroxamic acid (1^1}^}}〇111^, The aqueous solution of D (:1, USA) is the standard 'take 2〇μΐ sample and standard, add 40 μΐ isopropanol and 20 μΐ oxidant solution (mixture of mash and mash (ν/ν = 4 /1) ; sputum: acetic acid / citrate buffer (ρ Η = 6 〇) containing 57 g of sodium acetate (Showa), 37.5 g of trisodium citrate (Wako, Japan), 5.5 g of citric acid (Riedel-de Hagn, Germany), 385 ml of isopropanol; solution B: 7 0/0 chloramines T solution (Sigma), reaction for 5 minutes; add Ehrlich's reagent solution 260 μΐ, The absorption value (wavelength: 550 nm) was measured by a micro-reader (micr〇reader, £ max, Molecular devices, USA) after 17 hours in the dark/protected reaction. The calibration curve was prepared from the standard, and then This calibration curve is used to quantify the content of hydroxyproline in the sample. The collagen content in the sample is 1 〇χ hydroxyproline content. The calculated results are shown in the table. The results obtained in Table 4 show that the experimental group has a larger amount of collagen. Based on the above results, it can be known that the biomedical materials of the present invention are better than the conventional chitosan film for hGF or hSF. The cell attaching effect 'can promote the secretion of the cell matrix (this can be known by the results of glucosamine poly-and collagen). Example 6 is a solution of the chitosan solution obtained in the first embodiment. Or a solution of a chitosan solution containing nano-particles on an etched wafer having a width, a width of 2 μm, and a depth of 3 μm, which is to be dried and placed in a %-well culture dish' and covered with a glass cover glass As a control group, each mouse was covered with a cell density of 5xio4celis/ml, and 1 ml of cell liquid was added to the well, and the cells were placed at 37t:, 5% c, and 3/0 of the parent. Culture in the incubator. After observing 24+, 'observe the cell sorting situation. The result is as shown in the third figure. As shown in the third figure, it can be seen that the accelerated cell elongation and movement are added to align the groove i. J = The results show that the biomedical materials of the present invention are indeed aligned The migration and subtraction of the stem cell, the stem cell is used in Example 7. The chitosan solution obtained in the first embodiment is used to obtain the rice metal animal as Sprague-Dawley by spin drying. Rats, after anesthesia, shaved off the hair on the back' and cut a wound with an area of 0.8 cm x 88 cm on the back with a depth of 2 mm. The wound was covered with the same sample as described above, which contained different doses of aFGF (〇, 1〇, 50, 1〇〇). By day 14, the tissue near the implant was removed, fixed, embedded, and stained with hematoxy lin-eosin (H&E), and the results are shown in the fourth panel. Epithelialization refers to the healing of the epidermal layer of the skin (ie, the uppermost layer of the skin), that is, the skin wound is nearly completely healed. It can be seen from ^4 that the epithelialization of the experimental group is complete (as indicated by the arrow). ^ Shows that the biomedical materials of the present invention promote wound healing. Example 8 The sample of Example 1 (diameter 75 mm) was placed in deionized water of i (nine), and deionized water containing no sample was used as a blank group. Add 3 ml of 32 M 2'2-dipheny M-picrylhydrazyl (DPPH) free radical (dissolved in methanol) to deionized water, mix at room temperature for 90 minutes, then Ultraviolet/visible spectrophotometer (UV/VIS spectrophotometer) measures the absorbance at 515 nm; Then, the radical scavenging rate (%) is converted into the formula (I) to evaluate the anti-free radical and anti-oxidation ability of the sample. The higher the value, the more resistant the sample is to anti-free radicals and antioxidants. Free radical capture rate (%) = wide ( \ 'N 1 - absorbance of the sample (absorbance of the blank group V; XI00% (I)) Purification of the mononuclear sphere by centrifugation of human blood with Percoll 'And RPMI-1640 medium containing 10% fetal bovine serum (FBS) and 1% (v / ν) antibiotics (100 〇〇 U / ml penicillin (picillin) and 10 mg / ml streptomycin) (Gibco) was cultured. One to five single-nuclear spheres were added to the wells of each of the 24-well culture plates containing the sample of Example 1, and cultured for 96 hours. The monocyte changes attached to the surface of the sample were counted using an inverted microscope. The ratio of macrophages, which is defined as the ratio of mononuclear sphere transformation, is used as an indicator of inflammatory effects. The lower the value, the lower the inflammatory response, immune response and foreign body reaction caused by the sample. Bacillus subtilis such as cz·//(10) was cultured overnight (bCRC 10447) in a shaker incubator (100 rpm) at 37 ° C. Washed with pbs, centrifuged (6500 rpm, 5 minutes), and then re-brided Suspended in 丨ml phosphate buffer solution (PBS) and diluted to 2χ1〇5~3xl〇6(CFU)/ml The sample prepared in Example 1 (7.5 mm in diameter) was placed in a test tube' and 1 ml of the aforementioned bacterial solution was added, followed by 9 ΐ nΐ nutrient medium (nutrient media, Bacto, France). After 12 hours of cultivation, counting The number of bacteria on the sample. The lower the value, the better antibacterial function of the sample. The test results of the free radical capture rate, mononuclear ball conversion rate and anti-caries property of the above-mentioned biomedical materials of the present invention are listed in Table 5. It can be seen from the results obtained in Table 5 that the biomedical materials of the present invention have good anti-free radical, anti-oxidation, anti-inflammatory effects, and have the functions of reducing the immune reaction, reducing the reaction of foreign substances, and having antibacterial properties. Embodiment 91323665 The hepatic artery was inserted into the liver, and the blood was allowed to flow out for 10 seconds. Then, the sample of Example 7 was pressed on the wound for 9 seconds and then removed, and the bleeding was observed. It was found that the hepatic artery of the control group continued to bleed. However, the hepatic portal vein of the experimental group has stopped bleeding. This result shows that the biomedical material of the present invention has a good effect of accelerating blood coagulation. ^ Example 10

The film having the groove on the surface in Example 6 was rolled into a tubular shape to serve as a nerve conduit. The sciatic nerve of Sprague-Dawley rats was cut 1 mm, and the nerve conduit was connected to the nerve gap. After six weeks, the rats were sacrificed, the nerve conduits were taken out, and the cross section of the central region of the nerve conduit was observed by H&E staining to observe the repair and connection of the nerves, and the results are shown in the fifth graph.

As can be seen from the fifth figure, the fifth figure (A) is a longitudinal section of the control group with a 40-fold magnification, which shows only a small piece of tissue, and the fifth figure (B) is a 400-fold magnification of the nerve. Catheter sections also showed no formation of myelin in the control group. Further, referring to Fig. 5(C), a longitudinal section photograph of the nerve catheter of the present invention after being implanted for six weeks and magnified 40 times. As can be seen from the figure, 'the nerve conduit of the present invention has a significantly more tissue repair situation', which indicates that there is a nerve connection in the center of the catheter, and a 400-fold enlarged tissue section (figure (D)) also shows that A small circle of myelin is formed. 20 1323665

Table 2 Contact angle of the film surface Contact angle of the material (°) Control group 44.6 ± 1,154 chitin poly-gold 40ppm 35.0 ± 1.732 chitin poly-it 30ppm 36.6 ± 1.527 chitosan - gold 20ppm 37.0 ± 1.000 Glycan-silver 200ppm 34.6 ± 0.577 chitin poly-silver 40ppm 32.0 ± 1.000 chitosan-silver 20ppm 35.6 ± 0.577 Table 1 Average roughness of the film surface measured by atomic force microscopy (Ra) Material roughness (nm Control group <3 nm chitosan II-gold 40ppm 3.229 chitin polyacetate-gold 30ppm 4.926 chitin poly 20ppm 3.879 chitin poly-silver 200ppm 5.189 chitin poly-st-silver 40ppm 5.104 chitin poly-silver 20ppm 4.012 Table 3 The number of cells of human gingival fibroblasts (hGF) on the surface of the membrane. Number of cells control group 16500±200 Chitosan-Gold 30ppm 29000±300 Chitin-Gold 20ppm 27000±350 Chitin Poly St - Silver 40ppm 23500 Earth 100 Chitin Poly It-Silver 20ppm 18000士 200 21 1323665

Table 4: Cellular mass of human gingival fibroblasts (hGF) on the surface of the membrane Glycosaminoglycan (pg/cell number) Collagen (pg/cell number) Control group 0.0007 0.000011 Chitin poly- vinegar-gold 40 ppm 0.0018 0.000015丁聚餹-金30ppm 0.0020 0.000013 丁丁聚藤-银40ppm 0.0015 0.000017 chitosan-silver 20ppm 0.0009 0.000013 Table 5 film anti-free radical and anti-inflammatory situation material free radical capture rate (%) single nuclear ball transformation (activation) ratio (%) Bacterial attachment per unit area (CFU/cm2) Control group 15% 30% 2700 Experimental group - Gold 40 ppm 23% 7% 720 Experimental group - Silver 40 ppm 20% 17% 100

22 1323665 [Simple description of the diagram] The first picture is a photomicrograph of a micro-butanose film containing nano-gold or nano-silver observed by atomic force microscopy (AFM); (A) Chitosan with 40 ppm of nano-gold a sugar film; (B) a chitosan film containing 40 ppm of nano silver; (C) a chitosan film containing no nano gold or silver;

The first picture is a photograph of the surface of the film observed by a phase difference (day phase) microscope (phase valence microscope); (A) a chitosan film containing no nano gold or silver; (B) containing 40 ppm na The micro-butanose film of Mijin; the third picture shows the alignment of the growth of mouse brain neural stem cells on the film; (A) the chitosan film containing no nano gold or silver; (B) 40 a chitosan film of ppm nano gold;

Figure 4 is a photograph of a section of tissue surrounding the implant after 14 days of implantation of the biomedical material of the present invention; (A) a chitosan film containing no nano gold or silver; (B) containing 40 ppm The nano-butanose film of nanogold; the fifth picture is a photograph of the cross section of the central region of the nerve conduit after 6 weeks of implantation; (A) a chitosan film containing no nano gold or silver (4) 〇χ); (Β) contains no nano-gold or silver chitosan __χ); (C) a film containing 40 ppm of nano-gold (4〇χ); 1323665 (D) contains 40 Phenol nano-gold butyl vinegar film (40 〇χ). [Main component symbol description] None

twenty four

Claims (1)

% /7 X. Patent application scope: I A biomedical material, comprising: a matrix based on a molecular material, and the polymer material is chitosan, modified chitosan or Collagen; and a plurality of biomedical nano metal particles such as nano gold or nano silver, wherein the nano metal particles are dispersed in the matrix to form nanocrystal grains and a microcrystalline structure, wherein the nanometer The particles account for 0.0005% to 5% (w/w) of the total amount of the biomedical material, but do not include 1% to 5% (w/w). 2. The biomedical material as described in item 1 of the patent scope of the invention, wherein the particle size of the nanoparticle is b^Onm. 3. The biomedical material as described in claim 1 wherein the biomedical material is porous. 4. The biomedical material according to claim 1, wherein the biomedical material surface has a plurality of micro-trench structures, the micro-trench structures are parallel to each other, and the micro-trench structures have nerves The cells sort the growth of the micron-sized width, spacing and depth to promote regeneration of nerve cells. 5. A wound dressing for promoting wound healing and having an antibacterial effect, comprising the biomedical material as described in the scope of the patent application. 6. A wound dressing for accelerating blood coagulation comprising a biomedical material as described in claim 1 of the patent application. 7. A nerve conduit made of the biomedical material as described in claim 1 of the patent application. 25