Soft tissue repair material as well as preparation method and application thereof

Abstract

The invention relates to the technical field of soft tissue repair materials, in particular to a soft tissue repair material and a preparation method and application thereof. The invention relates to a polyurethane elastomer, which is prepared from an alternating block copolymer, the alternating block copolymer is obtained by reaction of polyester polyol, polyether polyol and diisocyanate, the use amount of diisocyanate accounts for 4-12% of the total mass of polyether polyol, polyester polyol and diisocyanate, and the use amount of polyurethane accounts for 1-5% of the total mass of polyether polyol, polyester polyol and diisocyanate. The diisocyanate is at least one or a combination of lysine diisocyanate and 1, 4-butane diisocyanate. The soft tissue repair material has an excellent repair effect and can be completely biodegraded, a degradation product cannot cause adverse reaction in vivo, and the soft tissue repair material is free of immunogenicity, has good biocompatibility and mechanical performance and can meet the core requirement of the soft tissue repair material.

Description

Technical Field

[0001] This invention relates to the field of soft tissue repair materials technology, and more specifically, to soft tissue repair materials, their preparation methods, and their applications. Background Technology

[0002] Soft tissue injury refers to traumatic conditions of the skin, muscles, ligaments, and other tissues outside the human skeleton caused by violence or chronic strain. Soft tissue repair materials are medical materials used to repair the above-mentioned injuries. Commonly used soft tissue repair materials mainly fall into the following categories: (1) Natural polymer materials, such as collagen and chitosan, which have the characteristics of promoting cell adhesion and antibacterial properties, but have problems such as insufficient mechanical strength or uncontrollable degradation rate. (2) Synthetic polymer materials, such as polyurethane and polylactic acid, have the advantages of being breathable, moisture-permeable, and biodegradable, but some materials may cause chronic inflammation or have mechanical properties that are not compatible with the repair site. (3) Bioactive materials, such as growth factors or stem cells, can accelerate tissue repair, but have problems such as high cost, harsh storage conditions, and potential tumorigenic risks. Therefore, it is necessary to provide a new soft tissue repair material that has mechanical properties that are compatible with the soft tissue being repaired, is non-immunogenic, can be completely degraded, and whose degradation products do not cause adverse reactions in the body.

[0003] In view of this, the present invention is proposed. Summary of the Invention

[0004] The purpose of this invention is to provide a soft tissue repair material, its preparation method, and its application. This soft tissue repair material exhibits good repair effects, is completely degradable, and its degradation products do not cause adverse reactions in vivo. The material is non-immunogenic and also possesses good biocompatibility and mechanical properties.

[0005] This invention is implemented as follows: In a first aspect, the present invention provides a soft tissue repair material prepared by alternating block copolymers, wherein the alternating block copolymers are obtained by reacting polyester polyols, polyether polyols and diisocyanates, wherein the amount of diisocyanate is 4-12% of the total mass of the polyether polyols, the polyester polyols and the diisocyanates, and the diisocyanate is at least one and a combination of lysine diisocyanate and 1,4-butane diisocyanate.

[0006] In an optional embodiment, the polyester polyol is prepared from at least one of polyethylene glycol butylene adipate, 1,6-hexanediol adipate, methyl-1,3-propanediol 1,6-hexanediol adipate, 1,6-diol neopentyl glycol decanted acid, and polycaprolactone; preferably, it is a polycaprolactone diol prepared from polycaprolactone.

[0007] In an optional embodiment, the polyether polyol includes at least one of polyethylene glycol, polypropylene glycol, and polytetrahydrofuran glycol; preferably polyethylene glycol.

[0008] In an optional embodiment, the number average molecular weight of the polycaprolactone diol is 2000-5000 Da, preferably 3000-4000 Da; In an optional embodiment, the number average molecular weight of the polyethylene glycol is 100-400 Da; preferably 200-300 Da.

[0009] In an optional embodiment, the soft tissue repair material meets at least one of the following requirements: (1) The degradation cycle is 4-8 weeks; (2) Porosity 30-80%, preferably 50-80%; (3) The thickness is 0.05-0.4 mm; (4) Tensile strength 15-40 MPa, elongation at break 85-260%, suture strength 7-16 N.

[0010] In an optional embodiment, the soft tissue repair material is at least one of a three-dimensional electrospun fiber layer, an oriented electrospun layer, an oriented electrospun monolayer, an oriented electrospun multilayer, and a cast film layer.

[0011] In a second aspect, the present invention provides a method for preparing the soft tissue repair material described in the foregoing embodiments, comprising: mixing and reacting polyester polyol, polyether polyol and diisocyanate to form an alternating block copolymer; The alternating block copolymer is processed using electrospinning and / or casting methods to form the soft tissue repair material.

[0012] In an optional embodiment, the step of forming the alternating block copolymer includes: mixing a polyether polyol and a diisocyanate and an organometallic catalyst and reacting them at 15-30°C for 20-48 hours to form a prepolymer intermediate; Then, the dehydrated polyester polyol is mixed with the prepolymer intermediate and reacted at 60-65°C for 20-48 hours to form an alternating block copolymer crude product. The crude alternating block copolymer is then post-processed.

[0013] In an optional embodiment, the reaction conditions for forming the alternating block copolymer meet the following requirements: (1) The molar ratio of the polyester polyol and the polyether polyol is 1:0.8 to 1:0.2; (2) The amount of the organometallic catalyst is 1-4% of the total mass of the polyether polyol and the diisocyanate.

[0014] Thirdly, the present invention provides the application of the soft tissue repair material described in the foregoing embodiments in the preparation of products for oral soft tissue repair, skin repair, or mucosal repair.

[0015] The present invention has the following beneficial effects: By specifically selecting diisocyanates and controlling their amount to form alternating block copolymers, the present invention enables the formation of soft tissue repair materials using these alternating block copolymers to have good soft tissue repair effects. The soft tissue repair materials are completely degradable, and the degradation products do not cause adverse reactions. Using these soft tissue repair materials will not cause inflammation or adhesions. Attached Figure Description

[0016] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 The diagram illustrates the surgical implantation process of the repair material provided for animal experiments of this invention, wherein the left image shows defect modeling, the middle image shows the implantation of the repair material, and the right image shows reverse suturing. Figure 2 Gross observation image 30 days post-surgery after surgical implantation of the repair material provided for animal experiments of this invention; Figure 3 HE staining results of the experimental group provided for animal experiments of this invention; Figure 4 The image shows the pathological analysis results of HE staining of the control group provided for the animal experiments of this invention. Detailed Implementation

[0018] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0019] Clinically, repair membranes used for oral soft tissue or mucosal repair generally require a tensile strength ≥3.7 MPa, an elongation at break ≥75%, and a suture tear force ≥4 N. Excessive or insufficient strength will affect the repair outcome. Simultaneously, an appropriate degradation rate is also necessary; ideally, the material should have completely degraded by the time the tissue has fully regenerated and regained its function. Too rapid a degradation rate will cause the repair site to lose support before the newly formed tissue has acquired sufficient mechanical strength, affecting the repair effect. Too slow a degradation rate will leave the material in the body for a long time after fulfilling its temporary scaffold function, leading to a series of problems, such as: 1. Chronic inflammatory response: the body continuously recognizes it as a foreign body, leading to long-term inflammatory cell infiltration; 2. Impeded tissue regeneration: the material occupies space, physically hindering the ingrowth and remodeling of new tissue; 3. Fibrous encapsulation formation: the body may attempt to encapsulate and isolate it with fibrous capsules, affecting its integration with surrounding tissues; 4. Increased risk of long-term complications: such as infection, displacement, or severe reactions caused by the generation of large amounts of debris in the later stages of degradation. The repair cycle of oral soft tissue or mucosa is not a fixed number of days but a dynamic physiological process. Typically, initial clinical healing (wound closure) takes about 2-4 weeks, while the maturation and remodeling of deep tissues can take weeks to months.

[0020] The soft tissue repair material provided in this invention has a tensile strength of 15-40 MPa, an elongation at break of 85-260%, and a suture strength of 5-16 N, which can meet the above clinical requirements. The degradation cycle is 4-8 weeks, which can ensure that the initial clinical healing has been completed and the maturation and remodeling of deep tissues have been basically completed. It will not cause chronic inflammation, will not hinder complete tissue regeneration, and will avoid risks such as complications.

[0021] Specifically, the present invention provides a soft tissue repair material, which is prepared by alternating block copolymers, wherein the alternating block copolymers are obtained by reacting polyester polyols, polyether polyols and diisocyanates, wherein the amount of diisocyanate accounts for 4-12% of the total mass of the polyether polyols, the polyester polyols and the diisocyanates, and the diisocyanate is at least one and a combination of lysine diisocyanate and 1,4-butane diisocyanate.

[0022] By limiting the specific diisocyanate and its dosage, the soft tissue repair material exhibits high biocompatibility, is non-immunogenic, and can effectively repair damaged soft tissue. Furthermore, the soft tissue repair material is completely degradable and causes no inflammation after use.

[0023] The amount of diisocyanate used is any value between 4% and 12% of the total mass of the polyether polyol, the polyester polyol, and the diisocyanate, such as 4%, 6%, 8%, 10%, 12%.

[0024] The polyether polyol includes one of polyethylene glycol (PEG), polypropylene glycol (PPG), and polytetrahydrofuran glycol (PTMEG); preferably polyethylene glycol. Its number-average molecular weight is 100-400 Da; for example, any value between 100-400 Da such as 100 Da, 200 Da, 250 Da, 300 Da, 350 Da, 400 Da; preferably 200-300 Da.

[0025] The polyester polyol is prepared from at least one of the following: poly(ethylene glycol butylene adipate) (PBGA), poly(hexanediol adipate) (PHA), poly(methyl-1,3-propanediol 1,6-hexanediol adipate) (PMHA), poly(1,6-diol neopentyl glycol adipate) (PHS), and polycaprolactone (PCL); preferably, it is a polycaprolactone diol prepared from polycaprolactone. The polycaprolactone has a number-average molecular weight of 50,000 to 200,000 Da, for example, any value between 50,000 Da, 60,000 Da, 70,000 Da, 80,000 Da, 90,000 Da, 100,000 Da, 110,000 Da, 120,000 Da, 130,000 Da, 140,000 Da, 150,000 Da, 160,000 Da, 170,000 Da, 180,000 Da, 190,000 Da, and 200,000 Da. Preferably, it has a molecular weight between 70,000 and 120,000 Da. The number average molecular weight of polycaprolactone diol is 2000-5000 Da, such as any value between 2000 Da, 2500 Da, 3000 Da, 3500 Da, 4000 Da, 4500 Da, 5000 Da, etc.; preferably 3000-4000 Da.

[0026] Using the above-mentioned material and molecular weight selection makes it easier to obtain the desired soft tissue repair material, which has good biocompatibility, excellent mechanical properties, no immunogenicity, and no adverse reactions in vivo due to degradation products.

[0027] Furthermore, the degradation cycle of the soft tissue repair material is 4-8 weeks; the porosity is 30-80%, preferably 50-80%; the thickness is 0.05-0.4 mm; the tensile strength is 15-40 MPa, the elongation at break is 85-260%, and the suture strength is 7-16 N.

[0028] This soft tissue repair material promotes cell growth and adheres well to the damaged area.

[0029] Furthermore, the soft tissue repair material is at least one of three-dimensional electrospun fiber layer, oriented electrospun layer, oriented electrospun monolayer, and oriented electrospun multilayer.

[0030] Secondly, the present invention provides a method for preparing the soft tissue repair material described in the foregoing embodiments, comprising: S1, forming alternating block copolymers; S1.1, forming polyester polyols; Polyesters (e.g., poly(ethylene glycol butylene adipate), poly(1,6-hexanediol adipate), poly(methyl-1,3-propanediol 1,6-hexanediol adipate), poly(1,6-diol neopentyl glycol decantedate), and polycaprolactone) are dissolved in organic solvent one (e.g., benzene-based solvents such as toluene) and added to a three-necked flask. The mass ratio of polyester to organic solvent one is controlled at 1:8-1:12. Toluenesulfonic acid is dissolved in organic solvent two (e.g., polyols such as 1,4-butanediol), and the molar ratio of polyester to organic solvent two is controlled at 1:2-1:7. The mass of toluenesulfonic acid is 1-3% of the total mass of polyester and organic solvent two. This solution is added to the three-necked flask, and the reaction is carried out at 70-80°C for 3-8 hours. After the reaction product cools to room temperature, it is washed three times with ice water. The resulting lower layer liquid was distilled under reduced pressure for 30 min. The remaining liquid was poured into a mixture of methanol and ice-cold distilled water to wash the precipitate, maintaining a methanol to distilled water volume ratio of 1:9. After washing twice, the mixture was filtered to obtain a polyester polyol (e.g., polycaprolactone diol).

[0031] S1.2, End sealing; Dehydrated polyether polyol (e.g., PEG) and an organometallic catalyst (e.g., non-tin organometallic catalyst: organobismuth) are dissolved in organic solvent three (e.g., polyhalogenated C1-C3 alkanes such as dichloroethane). Diisocyanate dissolved in organic solvent three is added dropwise to the above solution. The reaction is carried out at 15-30°C for 20-48 h. After the reaction is completed, the mixture is distilled under reduced pressure to obtain a prepolymer intermediate. The molar ratio of the polyester polyol to the polyether polyol is 1:0.8-1:1.2; the amount of the organometallic catalyst is 1-4% of the total mass ratio of the polyether polyol and the diisocyanate.

[0032] S1.3, Synthesis reaction; The prepolymer intermediate and the dehydrated polyester polyol were reacted in organic solvent 3 at 60-65℃ for 20-48 h. After the reaction was completed, heating was stopped, and the mixture was cooled to 45-55℃ and distilled under reduced pressure to obtain the crude product material.

[0033] The embodiments of the present invention can obtain alternating block copolymers with the required degradation time and mechanical properties by controlling the reaction temperature and reaction time, thereby ensuring the performance of the formed soft tissue repair material.

[0034] S1.4 Post-processing; After cooling the crude product material obtained from the synthesis of S1.3 to room temperature (20-35°C), it was washed in a petroleum ether / methanol mixed solution, with the volume ratio of methanol to petroleum ether controlled at 1:2-1:10. After washing, the product was filtered, and the solid was dried at 30-40°C under vacuum for 24-72 h until constant weight was obtained, yielding an alternating block copolymer.

[0035] The alternating block copolymer is processed using electrospinning and / or casting to form the soft tissue repair material. The electrospinning and / or casting methods are conventional procedures and will not be described in detail in this embodiment.

[0036] Thirdly, the present invention provides the application of the soft tissue repair material described in the foregoing embodiments in the preparation of tissue sutures for skin or oral mucosa.

[0037] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0038] Example 1 This invention provides a method for preparing a soft tissue repair material, comprising: S1, forming alternating block copolymers; S1.1, Synthetic polyester polyols; Polycaprolactone (PCL) M n = 85000 Da) was dissolved in toluene and added to a three-necked flask, controlling the mass ratio of PCL to toluene at 1:10. p-Toluenesulfonic acid was dissolved in 1,4-butanediol, controlling the molar ratio of PCL to 1,4-butanediol at 1:5. The mass of p-toluenesulfonic acid was 2% of the total mass of PCL and 1,4-butanediol, and this solution was added to the three-necked flask. The reaction was carried out at 75°C for 5 h. After the reaction product cooled to room temperature, it was washed three times with ice water. The resulting lower layer was distilled under reduced pressure for 30 min. The remaining liquid was poured into a mixture of methanol and ice-cold distilled water to wash away the precipitate, controlling the volume ratio of methanol to distilled water at 1:9. After two washes, the mixture was filtered to obtain PCL-diol 3000.

[0039] S1.2, End sealing; 1,4-Butane diisocyanate (BDI) and lysine diisocyanate (LDI) were mixed in a 1:1 molar ratio and dissolved in 1,2-dichloroethane. The mixture was then added to a three-necked flask, maintaining a mass ratio of BDI and LDI to 1,2-dichloroethane of 1:5. Subsequently, dehydrated polyethylene glycol (…) was added… M n= 200 Da) and bismuth neodecanoate were added to a dropping funnel and dissolved in 1,2-dichloroethane. The mass ratio of PEG200 and bismuth neodecanoate to the volume ratio of 1,2-dichloroethane was controlled at 1:10, and the molar ratio of the total molar amount of BDI and LDI to PEG200 was controlled at 2:1. The amount of bismuth neodecanoate was 2% of the total mass of PEG200, BDI and LDI. The mixture was slowly added dropwise to a three-necked flask at 30°C and reacted for 18 h. After the reaction was completed, the mixture was distilled under reduced pressure for 20 min, and the remaining solution was added to a dropping funnel to obtain the prepolymer intermediate.

[0040] S1.3, Synthesis reaction; The dehydrated PCL-diol 3000 was added to a three-necked flask and dissolved in 1,2-dichloroethane, maintaining a mass ratio of PCL-diol 3000 to 1,2-dichloroethane of 1:10. The remaining solution obtained in step 1 was slowly added dropwise to the three-necked flask, maintaining a molar ratio of PEG to PCL-diol of 1:1. The reaction was carried out at 65°C for 25 h. After the reaction was completed, the product was cooled to 50°C and then distilled under reduced pressure for 30 min. The above proportions resulted in BDI and LDI accounting for 10.27% of the total mass of PEG, PCL-diol, BDI, and LDI.

[0041] 4. Post-processing; After vacuum distillation, the product was cooled to 20-35℃ and then added to a petroleum ether / methanol mixed solution to wash the precipitate. The volume ratio of petroleum ether to methanol was controlled at 4:1. After washing the precipitate twice, the product was filtered and the filter residue was vacuum dried at 35℃ for 72 h to obtain the biodegradable material (hereinafter referred to as PCL-PEG).

[0042] S2, electrospinning; The PCL-PEG material obtained in step S1 was dissolved in tetrahydrofuran (THF). N , N An electrospinning solution was prepared by mixing THF and DMF in a dimethylformamide (DMF) solution. This solution, by mass percentage, consists of the following components: 30% biodegradable material, and the remainder is a mixture of THF and DMF. THF:DMF (v / v) = 1:1.

[0043] The distance between the nozzle and the receiver was adjusted to (20±1) cm; the receiver rotation speed was set to (350±100) rpm / min; the nozzle injection speed was set to (0.25±0.05) mL / min; the nozzle translation speed was set to (400±50) mm / min, and the translation distance was set to (180±50) mm; the negative voltage was set to (-3±0.5) kV, and the positive voltage was set to (11±0.5) kV. A 22G needle (inner diameter 0.41 mm) was used as the nozzle head. Electrospinning time: 4 h. An electrospun layer with a thickness of 0.26 mm was obtained, which is the initial product of the soft tissue repair material. The initial product was freeze-dried or soaked in water until the total amount of solvent residue in the initial product was ≤0.1%; then dried until the moisture residue in the initial product was ≤0.5%; the rough edges or uneven thickness of the dried initial product were removed, and it was cut into the required size, which is the finished product.

[0044] Examples 2-4 and Comparative Examples 1-4 Examples 2-4 and Comparative Examples 1-4 also provide a method for preparing a soft tissue repair material. The preparation method is basically the same as the preparation method provided in Example 1, except that some conditions are different. The specific different conditions are shown in Table 1 below. All other conditions are the same as in Example 1.

[0045]

[0046] Test Example 1 The soft tissue repair materials of Examples 1-4 and Comparative Examples 1-4 were subjected to degradation period tests. The degradation period test method is as follows: Prepare PBS buffer using sterile double-distilled water, then add CaCl2, type I collagenase, lipase, protease, and α-amylase to prepare a buffer with a CaCl2 concentration of 10 mM, a type I collagenase concentration of 2 U / mL, a lipase concentration of 0.5 U / mL, a protease concentration of 1 U / mL, and an α-amylase concentration of 2 U / mL. Adjust the pH value to 6.8 ± 0.2.

[0047] The soft tissue repair material was vacuum dried to constant weight. The weight of the sample was accurately measured and recorded as m1. The sample was then placed in a sterilized 20 mL sample bottle (the ratio of buffer volume to sample mass should be greater than or equal to 30:1). Buffer was added, and the centrifuge tube was placed in a constant temperature shaking incubator with the temperature set at 37°C and the shaking speed at 100 rpm.

[0048] Remove the sample from the buffer solution, dry it in a vacuum desiccator until it reaches a constant weight, and then weigh it. Record the weight as m2.

[0049] Mass loss = (m1-m2) / m1×100% The mass loss of the sample was measured. The time point at which the mass loss reached 100% is the degradation cycle of the sample.

[0050] The results are shown in the table below.

[0051]

[0052] Mechanical properties of the soft tissue repair materials of Examples 1-4 and Comparative Example 5 were tested. Comparative Example 5 was the same as the control in the animal experiment below, which was the commercially available oral repair membrane. The structure and composition of this product is a xenogeneic decellularized dermal matrix prepared from bovine skin tissue after a series of treatments. The main component is collagen, which can be degraded in vivo.

[0053] Test Example 2 The testing method is as follows: (1) Tensile strength: First, cut the above-mentioned dry samples into multiple specimens with appropriate width, flat edges, parallel sides and no visible defects. Then, turn on the universal testing machine, set the parameters, perform tensile strength test, and process the data.

[0054] (2) Elongation at break: First, cut the above-mentioned dry samples into multiple specimens with appropriate width, flat edges, parallel sides and no visible defects. Then, turn on the universal testing machine, set the parameters, conduct the elongation at break test, and process the data. The formula for calculating the elongation at break is: (elongation at break of the diaphragm / original length of the diaphragm) × 100%.

[0055] (3) Suture strength: First, cut the above-mentioned dry samples into multiple specimens with appropriate width, flat edges, parallel sides and no visible defects. Then, use the selected specification of suture thread to sew one end of the sample with two needles and tie it. Suture multiple oral repair membrane specimens in the same way. Then, use a universal testing machine to clamp the sample and test the suture strength at the suture joint to obtain the test data.

[0056] The test results are as follows:

[0057] Based on the above results, it can be seen that the mechanical properties of the soft tissue repair material provided in this application embodiment are significantly better than those of Comparative Example 5.

[0058] Animal experiments Beagles aged 10-18 months were selected for animal experiments.

[0059] In experimental animals, buccal soft tissue (oral mucosa) defects were randomly created on both sides, forming defects of approximately 13 mm × 16 mm. In the experimental group, the test instrument (the soft tissue repair material from Example 1) was cut to a size of 17.5 mm × 20 mm, placed at the defect site, and then sutured. In the control group, the control product (a commercially available oral repair membrane, whose structure and composition are xenogeneic acellular dermal matrix prepared from bovine skin tissue through a series of treatments, with collagen as its main component, and degradable in vivo) was cut to a size of 17.5 mm × 20 mm, placed at the defect site, and then sutured. The surgical implantation procedure is described in [link to surgical procedure]. Figure 1 Yellow gauze was used to cover the material to prevent animals from licking it off.

[0060] Gross observation image taken 30 days post-surgery. Figure 2 The right image shows a gross observation of the device implanted with the test instrument, while the left image shows a gross observation of the control sample implanted with the test instrument. According to... Figure 2 As observed, both the experimental and control groups showed good wound healing with no adverse reactions such as redness, swelling, or infection. The boundary between the wound and the surrounding normal tissue was relatively blurred, and no material degradation residue was observed. The soft tissue repair material provided in this embodiment of the invention can complete soft tissue repair without any material degradation residue.

[0061] HE staining analysis See Figure 3 The results were satisfactory. Thirty days post-surgery, HE staining was performed on the repaired buccal soft tissue (oral mucosa) defects in both the experimental and control groups. The results are shown in [link to results]. Figure 3 and Figure 4 .in, This indicates the viewfinder area when using a high-powered lens (400×). Polymorphonuclear leukocytes; Lymphocytes; Macrophages; New blood vessels.

[0062] according to Figure 3 It was observed that the newly formed epidermal cells at the implantation site underwent terminal differentiation into distinct stratified squamous epithelium with a relatively smooth surface; the dermal fibrous connective tissue had recovered to its normal structure, was densely arranged, and neovascularization was visible, indicating that the tissue had essentially healed. A very small amount of inflammatory cell infiltration was observed, with cell type and quantity referenced in the scoring; no tissue necrosis or other lesions were observed. No material degradation residue was found.

[0063] according to Figure 4It was observed that the newly formed epidermal cells at the implantation site underwent terminal differentiation into distinct stratified squamous epithelium with a relatively smooth surface; the dermal fibrous connective tissue had recovered to its normal structure, was densely arranged, and neovascularization was visible, indicating that the tissue had essentially healed. A very small amount of inflammatory cell infiltration was observed, with cell type and quantity referenced in the scoring; no tissue necrosis or other lesions were observed. No material degradation residue was found.

[0064] The control sample is a xenogeneic decellularized dermal matrix prepared from bovine skin tissue through a series of treatments. Its main component is collagen, which is an animal-derived repair material. It may have immunogenicity issues. However, the repair material provided in this embodiment of the invention not only has a degradation cycle that matches clinical requirements and superior mechanical properties compared to the control sample repair material, but also does not have immunogenicity issues.

[0065] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A soft tissue repair material, characterized in that, It is prepared by alternating block copolymers, wherein the alternating block copolymers are obtained by reacting polyester polyols, polyether polyols and diisocyanates, wherein the amount of diisocyanate is 4-12% of the total mass of the polyether polyol, the polyester polyol and the diisocyanate, and the diisocyanate is at least one or a combination of lysine diisocyanate and 1,4-butane diisocyanate.

2. The soft tissue repair material according to claim 1, characterized in that, The polyester polyol is prepared from at least one of polyethylene glycol butylene adipate, 1,6-hexanediol adipate, methyl-1,3-propanediol 1,6-hexanediol adipate, 1,6-diol neopentyl glycol adipate, and polycaprolactone; preferably, it is a polycaprolactone diol prepared from polycaprolactone.

3. The soft tissue repair material according to claim 2, characterized in that, The polyether polyol includes at least one of polyethylene glycol, polypropylene glycol, and polytetrahydrofuran glycol; preferably polyethylene glycol.

4. The soft tissue repair material according to claim 3, characterized in that, The number average molecular weight of the polycaprolactone diol is 2000-5000 Da, preferably 3000-4000 Da; Preferably, the number average molecular weight of the polyethylene glycol is 100-400 Da; more preferably, it is 200-300 Da.

5. The soft tissue repair material according to claim 1, characterized in that, The soft tissue repair material meets at least one of the following requirements: (1) The degradation cycle is 4-8 weeks; (2) Porosity 30-80%, preferably 50-80%; (3) The thickness is 0.05-0.4 mm; (4) Tensile strength 15-40 MPa, elongation at break 85-260%, suture strength 7-16 N.

6. The soft tissue repair material according to claim 1, characterized in that, The soft tissue repair material is at least one of the following: a three-dimensional electrospun fiber layer, an oriented electrospun layer, an oriented electrospun monolayer, an oriented electrospun multilayer, and a cast film layer.

7. A method for preparing the soft tissue repair material according to claim 1, characterized in that, include: Polyester polyols, polyether polyols and diisocyanates are mixed and reacted to form alternating block copolymers; The alternating block copolymer is processed using electrospinning and / or casting methods to form the soft tissue repair material.

8. The preparation method according to claim 7, characterized in that, The steps for forming the alternating block copolymer include: mixing a polyether polyol and a diisocyanate and an organometallic catalyst and reacting them at 15-30°C for 20-48 hours to form a prepolymer intermediate; Then, the dehydrated polyester polyol is mixed with the prepolymer intermediate and reacted at 60-65°C for 20-48 hours to form an alternating block copolymer crude product. The crude alternating block copolymer is then post-processed.

9. The preparation method according to claim 8, characterized in that, The reaction conditions for forming the alternating block copolymer must meet the following requirements: (2) The molar ratio of the polyester polyol and the polyether polyol is 1:0.8-1:1.2; (3) The amount of the organometallic catalyst is 1-4% of the total mass of the polyether polyol and the diisocyanate.

10. The use of the soft tissue repair material of claim 1 in the preparation of products for oral soft tissue repair, skin repair or mucosal repair.

Images