Polymeric tissue repair material and method of making same

Abstract

The application discloses a kind of tissue repair materials and preparation method thereof, the preparation method of tissue repair material includes the following steps: respectively with first tissue repair polymer, second tissue repair polymer and third tissue repair polymer as solute, first electrospinning solution, second electrospinning solution and third electrospinning solution are prepared, and blend fiber membrane is obtained after twice electrospinning;Blending fiber membrane is dried, and the required tissue repair material is obtained.The preparation method of tissue repair material of the application, with the first tissue repair polymer, the second tissue repair polymer and the third tissue repair polymer different from each other in degradation period, so that the tissue repair material prepared can be realized step-by-step degradation when using, so that its degradation period is matched with soft tissue repair period, so that it can match the multi-stage repair process of tissue (especially soft tissue), provide whole process protection for the repair of soft tissue, without additional burden.

Description

Technical Field

[0001] This invention relates to the field of tissue repair, and in particular to a polymeric tissue repair material and its preparation method. Background Technology

[0002] Soft tissue repair is a crucial component of surgical procedures, especially vital for recovery after surgery or trauma. Currently, the main soft tissue repair materials on the market include natural polymers, synthetic polymers, metals, ceramics, and organic-inorganic composites. These materials play their respective roles at different stages of soft tissue repair, such as hemostasis, inflammation repair, support and shaping, and tissue regeneration.

[0003] Natural polymers, such as chitosan, hyaluronic acid, and collagen, are widely used in soft tissue repair due to their excellent biocompatibility and cell-friendly properties. Synthetic polymers, such as polyethylene glycol and polylactic acid, also play a role in soft tissue repair due to their controllable biodegradability and mechanical properties. Metallic materials mainly play a role in providing structural support and promoting healing, while ceramic materials play a role in assisting hard tissue repair due to their good biocompatibility and wear resistance.

[0004] However, existing technologies have some limitations in the application of soft tissue repair materials. Specifically, existing soft tissue repair materials are usually prepared by using a single material through a simple fiber interlacing structure. The degradation cycle of a single material is fixed, which cannot match the multi-stage repair process. At the same time, the simple fiber interlacing structure cannot monitor cell growth and can only achieve a simple barrier protection function. Summary of the Invention

[0005] Therefore, it is necessary to provide a method for preparing tissue repair materials that can solve the above problems.

[0006] In addition, it is necessary to provide tissue repair materials prepared by the aforementioned methods.

[0007] A method for preparing a tissue repair material includes the following steps: A first electrospinning solution, a second electrospinning solution, and a third electrospinning solution were prepared using a first tissue repair polymer, a second tissue repair polymer, and a third tissue repair polymer as solutes, respectively, wherein the degradation cycles of the first tissue repair polymer, the second tissue repair polymer, and the third tissue repair polymer are different from each other; The first electrospinning solution, the second electrospinning solution, and the third electrospinning solution are injected into a syringe, respectively. A pump propels the syringe to perform a first electrospinning, causing the first, second, and third electrospinning solutions injected into the syringe to spin first, second, and third filaments, respectively. A cylindrical metal rotating receiving disk receives the first, second, and third filaments, allowing the first, second, and third filaments to be blended and spun to obtain a first semi-finished product. The first electrospinning time is 3 to 5 minutes, the injection speed of the first electrospinning solution is 1 mL / h to 3 mL / h, the injection speed of the second electrospinning solution is 1 mL / h to 3 mL / h, the injection speed of the third electrospinning solution is 4 mL / h to 6 mL / h, the applied voltage is 10 kV to 20 kV, the receiving distance is 5 cm to 15 cm, and the rotation speed of the cylindrical metal rotating receiving disk is 700 r / h to 2000 r / h. After the first electrospinning is completed, the propulsion pump continues to advance the syringe for a second electrospinning, so that the first, second, and third electrospinning solutions injected into the syringe respectively spin the fourth, fifth, and sixth fibers. The cylindrical metal rotating receiving disk continues to receive the fourth, fifth, and sixth fibers, so that the fourth, fifth, and sixth fibers continue to be blended and spun to obtain a second semi-finished product. The second semi-finished product and the first semi-finished product form a blended fiber membrane. The second electrospinning time is 3 min to 5 min, the injection speed of the first electrospinning solution is 1 mL / h to 3 mL / h, the injection speed of the second electrospinning solution is 1 mL / h to 3 mL / h, the injection speed of the third electrospinning solution is 1 mL / h to 3 mL / h, the applied voltage is 15 kV to 25 kV, the receiving distance is 15 cm to 25 cm, and the rotation speed of the cylindrical metal rotating receiving disk is 700 r / h to 2000 r / h. The blended fiber membrane is dried to obtain the desired tissue repair material.

[0008] In one embodiment, the diameter of the first spun yarn is 2.5±0.5μm, the diameter of the second spun yarn is 3.0±0.5μm, and the diameter of the third spun yarn is 5.0±1.0μm; the porosity of the first semi-finished product is 70±5%, and the pore size of the first semi-finished product is 10-50μm.

[0009] In one embodiment, the diameter of the fourth spinning is 1.5±0.3μm, the diameter of the fifth spinning is 2.0±0.5μm, and the diameter of the sixth spinning is 4.0±1.0μm; the porosity of the second semi-finished product is 30±5%, and the pore size of the second semi-finished product is 50-200μm.

[0010] In one embodiment, the mass ratio of the first spinning, the second spinning, the third spinning, the fourth spinning, the fifth spinning, and the sixth spinning is (20-25):(15-20):(10-15):(15-20):(10-15):(5-10).

[0011] In one embodiment, the second semi-finished product is stacked on the first semi-finished product to form a flat or tubular composite structure, wherein the inner diameter of the tubular structure is 3mm to 15mm.

[0012] In one embodiment, the mass concentration of the first electrospinning solution is 8% to 12%, the mass concentration of the second electrospinning solution is 5% to 9%, and the mass concentration of the third electrospinning solution is 15% to 25%.

[0013] In one embodiment, the first tissue repair polymer is polycaprolactone-polyethylene glycol-polycaprolactone, the second tissue repair polymer is polylactide, and the third tissue repair polymer is poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine.

[0014] In one embodiment, the solvent of the first electrospinning solution is dioxane or dimethylformamide, the solvent of the second electrospinning solution is dioxane or dimethylformamide, and the solvent of the third electrospinning solution is dioxane or dimethylformamide.

[0015] In one embodiment, the operation of drying the blended fiber membrane is as follows: after vacuum drying the blended fiber membrane to remove residual liquid, the blended fiber membrane is placed in a vacuum drying oven for drying for 36h~48h.

[0016] A tissue repair material is prepared by the above-described method for preparing tissue repair materials.

[0017] The method for preparing the tissue repair material of the present invention uses a first tissue repair polymer, a second tissue repair polymer, and a third tissue repair polymer with different degradation cycles. This allows the prepared tissue repair material to undergo stepwise degradation during use, matching its degradation cycle with the soft tissue repair cycle. This allows it to match the multi-stage repair process of tissues (especially soft tissues), providing full-process protection for soft tissue repair without additional burden.

[0018] Furthermore, the preparation method of the tissue repair material of the present invention obtains fiber membranes with different porosities, pore sizes and fiber diameters (i.e., the first semi-finished product and the second semi-finished product) by adjusting the parameters in two electrospinning processes. The high porosity (70%) of the first semi-finished product promotes early adhesion of tissue cells, while the low porosity (30%) of the second semi-finished product provides long-term mechanical support. The two work together to match the soft tissue repair cycle, so that the prepared tissue repair material has a biomimetic fiber structure similar to the extracellular matrix, which can promote cell adhesion and proliferation. While playing a barrier and protective role, it can also effectively reduce postoperative inflammatory response.

[0019] The tissue repair material prepared by the method of the present invention can automatically adhere under human body temperature and when immersed in tissue fluid, without the need for suture fixation, simplifying surgical procedures and making the operation convenient.

[0020] Preferably, the third tissue repair polymer is poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine. The poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine obtained by block modification of two materials with different glass transition temperatures has a glass transition temperature of 35.5±0.5℃ as determined by differential scanning calorimetry (DSC). It can automatically curl and adhere at human body temperature (36-38℃). The innovative glass transition temperature design enables automatic adhesion at human body temperature. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] in: Figure 1 This is a flowchart illustrating a method for preparing a tissue repair material according to one embodiment.

[0023] Figure 2 This is a histological examination result of hypertrophic scar formation in a wound obtained from a test case.

[0024] Figure 3 The image shows the SEI and ETI indices of hypertrophic scars obtained in the test case.

[0025] Figure 4 This is a graph showing the in vitro degradation results of the tissue repair material prepared in Example 1. Detailed Implementation

[0026] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] Combination Figure 1 This invention discloses a method for preparing a tissue repair material according to one embodiment, comprising the following steps: S10. Prepare a first electrospinning solution, a second electrospinning solution, and a third electrospinning solution using the first tissue repair polymer, the second tissue repair polymer, and the third tissue repair polymer as solutes, respectively.

[0028] The degradation cycles of the first tissue repair polymer, the second tissue repair polymer, and the third tissue repair polymer are different from each other.

[0029] Preferably, in this embodiment, the mass concentration of the first electrospinning solution is 8%~12%, the mass concentration of the second electrospinning solution is 5%~9%, and the mass concentration of the third electrospinning solution is 15%~25%.

[0030] Generally, the first, second, and third tissue repair polymers can be synthetic polymer materials, such as: polycaprolactone-polyethylene glycol-polycaprolactone (PCEC), poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine (PEG-MELG), polylactide (PLLA), poly(lactic-co-glycolic acid) copolymer (PLGA), polylactic-polyethylene glycol block copolymer (PELA), etc.

[0031] Specifically, this application breaks through the limitations of single materials. By studying the biocompatibility and degradation cycle of different materials, it ultimately selected polycaprolactone-polyethylene glycol-polycaprolactone as the first tissue repair polymer, polylactide as the second tissue repair polymer, and poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine as the third tissue repair polymer. The three different materials are combined in a specific ratio to achieve an ordered material composition. This allows the final tissue repair material to undergo stepwise degradation during use, matching its degradation cycle with the soft tissue repair cycle. This allows it to match the multi-stage repair process of tissues (especially soft tissues), providing comprehensive protection for soft tissue repair without additional burden.

[0032] The third tissue repair polymer is poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine. The poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine obtained by block modification of two materials with different glass transition temperatures allows it to automatically curl at 36℃~38℃. The innovative glass transition temperature design enables automatic adhesion under human body temperature environment.

[0033] Specifically, in this embodiment, the mass concentration of the first electrospinning solution is 10%, the mass concentration of the second electrospinning solution is 7%, and the mass concentration of the third electrospinning solution is 20%.

[0034] Preferably, in this embodiment, the solvent of the first electrospinning solution is dioxane or dimethylformamide, the solvent of the second electrospinning solution is dioxane or dimethylformamide, and the solvent of the third electrospinning solution is dioxane or dimethylformamide.

[0035] S20. The first electrospinning solution, the second electrospinning solution, and the third electrospinning solution are injected into the syringe respectively. The propulsion pump propels the syringe to perform the first electrospinning, so that the first electrospinning solution, the second electrospinning solution, and the third electrospinning solution injected into the syringe are spun into the first spun yarn, the second spun yarn, and the third spun yarn respectively. The cylindrical metal rotating receiving disk receives the first spun yarn, the second spun yarn, and the third spun yarn, so that the first spun yarn, the second spun yarn, and the third spun yarn are blended and spun to obtain the first semi-finished product.

[0036] The electrospinning process involves a first electrospinning time of 3-5 minutes, a first electrospinning solution injection rate of 1-3 mL / h, a second electrospinning solution injection rate of 1-3 mL / h, a third electrospinning solution injection rate of 4-6 mL / h, a loading voltage of 10-20 kV, a receiving distance of 5-15 cm, and a rotating receiving speed of 700-2000 r / h for the cylindrical metal rotating receiving disk.

[0037] Preferably, in this embodiment, high-voltage electrospinning technology is used to prepare a first semi-finished fiber membrane with special porosity and fiber diameter by controlling parameters such as the ejection speed of the electrospinning solution, the applied voltage, the receiving distance, and the rotation receiving speed of the cylindrical metal rotating receiving disk.

[0038] Preferably, in this embodiment, the diameter of the first spinning is 2.5±0.5μm, the diameter of the second spinning is 3.0±0.5μm, and the diameter of the third spinning is 5.0±1.0μm; the porosity of the first semi-finished product is 70±5%, and the pore size of the first semi-finished product is 10-50μm.

[0039] S30. After the first electrospinning is completed, the propulsion pump continues to propel the syringe for the second electrospinning, so that the first, second and third electrospinning solutions are injected into the syringe to spin the fourth, fifth and sixth fibers, respectively. The cylindrical metal rotating receiving disk continues to receive the fourth, fifth and sixth fibers, so that the fourth, fifth and sixth fibers continue to be blended and spun to obtain the second semi-finished product. The second semi-finished product and the first semi-finished product form a blended fiber membrane.

[0040] The second electrospinning time is 3 min to 5 min, the injection rate of the first electrospinning solution is 1 mL / h to 3 mL / h, the injection rate of the second electrospinning solution is 1 mL / h to 3 mL / h, the injection rate of the third electrospinning solution is 1 mL / h to 3 mL / h, the applied voltage is 15 kV to 25 kV, the receiving distance is 15 cm to 25 cm, and the rotation speed of the cylindrical metal rotating receiving disk is 700 r / h to 2000 r / h.

[0041] Preferably, in this embodiment, high-voltage electrospinning technology is used to prepare a second semi-finished fiber membrane with special porosity and fiber diameter by controlling parameters such as the ejection speed of the electrospinning solution, the applied voltage, the receiving distance, and the rotation receiving speed of the cylindrical metal rotating receiving disk.

[0042] Preferably, in this embodiment, the diameter of the fourth spinning is 1.5±0.3μm, the diameter of the fifth spinning is 2.0±0.5μm, and the diameter of the sixth spinning is 4.0±1.0μm; the porosity of the second semi-finished product is 30±5%, and the pore size of the second semi-finished product is 50-200μm.

[0043] Preferably, in this embodiment, the mass ratio of the first spinning, the second spinning, the third spinning, the fourth spinning, the fifth spinning, and the sixth spinning is (20-25):(15-20):(10-15):(15-20):(10-15):(5-10).

[0044] In particular, in this embodiment, the second semi-finished product is stacked on the first semi-finished product to form a flat or tubular composite structure, wherein the inner diameter of the tubular structure is 3mm to 15mm.

[0045] Specifically, in this embodiment, in order to ultimately make the prepared tissue repair material similar to the extracellular matrix structure, the extracellular matrix sections were scanned by an electron scanning microscope to obtain the structure of the extracellular matrix. Then, by adjusting the parameters in two electrospinning processes, fiber membranes with different porosities, pore sizes, and fiber diameters (i.e., the first semi-finished product and the second semi-finished product) were obtained. This makes the prepared tissue repair material have a biomimetic fiber structure similar to the extracellular matrix, which can promote cell adhesion and proliferation. While playing a barrier and protective role, it can also effectively reduce postoperative inflammatory response.

[0046] S40. Dry the blended fiber membrane to obtain the desired tissue repair material.

[0047] Specifically, in this embodiment, the operation of drying the blended fiber membrane is as follows: after vacuum drying the blended fiber membrane (48h) to remove residual liquid, the blended fiber membrane is placed in a vacuum drying oven for another 36h~48h.

[0048] The method for preparing the tissue repair material of the present invention uses a first tissue repair polymer, a second tissue repair polymer, and a third tissue repair polymer with different degradation cycles. This allows the prepared tissue repair material to undergo stepwise degradation during use, matching its degradation cycle with the soft tissue repair cycle. This allows it to match the multi-stage repair process of tissues (especially soft tissues), providing full-process protection for soft tissue repair without additional burden.

[0049] Furthermore, the preparation method of the tissue repair material of the present invention obtains fiber membranes (i.e., the first semi-finished product and the second semi-finished product) with different porosities, pore sizes and fiber diameters by adjusting the parameters in two electrospinning processes. This results in the prepared tissue repair material having a biomimetic fiber structure similar to the extracellular matrix, which can promote cell adhesion and proliferation. While playing a barrier and protective role, it can also effectively reduce postoperative inflammatory response.

[0050] The present invention also discloses a tissue repair material prepared by the above-described method for preparing tissue repair materials according to one embodiment.

[0051] The tissue repair material prepared by the method of the present invention can automatically adhere under human body temperature and when immersed in tissue fluid, without the need for suture fixation, simplifying surgical procedures and making the operation convenient.

[0052] The following are specific examples.

[0053] In a specific embodiment, polycaprolactone-polyethylene glycol-polycaprolactone (PCEC) was RESERMER® C 212 PEG-PCL-PEG purchased from Evonik, polylactide (PLLA) was PURASORB® PL 18 purchased from Corbion, and poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine (PEG-MELG) was a custom-made product purchased from Ivy Chemicals.

[0054] Example 1 1. Polycaprolactone-polyethylene glycol-polycaprolactone (PCEC), polylactide (PLLA), and poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine (PEG-MELG) were dissolved in dioxane or dimethylformamide (DMF) respectively, and stirred at room temperature for 18 hours to obtain three electrospinning solutions. The mass fraction of PCEC in the electrospinning solutions was 10%, the mass fraction of PLLA was 7%, and the mass fraction of PEG-MELG was 20%. The electrospinning solutions were injected into syringes for later use.

[0055] 2. The electrospinning solution injected into the syringe is electrospinned under the action of a propulsion pump. The injection rates of polycaprolactone-polyethylene glycol-polycaprolactone (PCEC) and polylactide (PLLA) are adjusted to 2 ml / h, and the injection rate of poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine (PEG-MELG) is adjusted to 5 ml / h. The applied voltage is 15 kV, the receiving distance is 10 cm, and a cylindrical metal rotating receiving disk is used to receive the electrospinning to obtain a blend of the three. The rotating receiving speed is adjusted to 1350 r / h. After 4 min, the injection rates of the three are adjusted to 2 ml / h, the solution is replenished in time, the applied voltage is adjusted to 20 kV, the receiving distance is 20 cm, and a cylindrical metal rotating receiving disk is used to receive the electrospinning. The rotating receiving speed is adjusted to 1350 r / h. After 4 min, a blend of the three is obtained.

[0056] 3. Collect the obtained blended fiber membranes and vacuum dry them for 48 hours to remove residual solvent; 4. Place the obtained blended fiber membrane in a vacuum drying oven and dry for 24 hours to obtain the desired tissue repair material.

[0057] Example 2 1. Polycaprolactone-polyethylene glycol-polycaprolactone (PCEC), polylactide (PLLA), and poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine (PEG-MELG) were dissolved in dioxane or dimethylformamide (DMF) respectively, and stirred at room temperature for 18 hours to obtain three electrospinning solutions. The mass fraction of PCEC in the electrospinning solutions was 8%, the mass fraction of PLLA was 9%, and the mass fraction of PEG-MELG was 15%. The electrospinning solutions were injected into syringes for later use.

[0058] 2. The electrospinning solution injected into the syringe is electrospinned under the action of the propulsion pump. The injection rates of polycaprolactone-polyethylene glycol-polycaprolactone (PCEC) and polylactide (PLLA) are adjusted to 1 ml / h, and the injection rate of poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine (PEG-MELG) is adjusted to 6 ml / h. The applied voltage is 10 kV, the receiving distance is 15 cm, and a cylindrical metal rotating receiving disk is used to receive the electrospinning to obtain a blend of the three. The rotating receiving speed is adjusted to 700 r / h. After 5 min, the injection rates of the three are adjusted to 1 ml / h, the solution is replenished in time, the applied voltage is adjusted to 25 kV, the receiving distance is 15 cm, and a cylindrical metal rotating receiving disk is used to receive the electrospinning. The rotating receiving speed is adjusted to 2000 r / h. After 3 min, a blend of the three is obtained.

[0059] 3. Collect the obtained blended fiber membranes and vacuum dry them for 48 hours to remove residual solvent; 4. Place the obtained blended fiber membrane in a vacuum drying oven and dry for 3 hours to obtain the desired tissue repair material.

[0060] Example 3 1. Polycaprolactone-polyethylene glycol-polycaprolactone (PCEC), polylactide (PLLA), and poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine (PEG-MELG) were dissolved in dioxane or dimethylformamide (DMF), respectively, and stirred at room temperature for 18 hours to obtain three electrospinning solutions. The mass fraction of PCEC in the electrospinning solutions was 12%, the mass fraction of PLLA was 5%, and the mass fraction of PEG-MELG was 25%. The electrospinning solutions were injected into syringes for later use.

[0061] 2. The electrospinning solution injected into the syringe is electrospinned under the action of the propulsion pump. The injection rates of polycaprolactone-polyethylene glycol-polycaprolactone (PCEC) and polylactide (PLLA) are adjusted to 3 ml / h, and the injection rate of poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine (PEG-MELG) is adjusted to 4 ml / h. The applied voltage is 20 kV, the receiving distance is 5 cm, and a cylindrical metal rotating receiving disk is used to receive the electrospinning to obtain a blend of the three. The rotating receiving speed is adjusted to 2000 r / h. After 3 min, the injection rates of the three are adjusted to 3 ml / h, the solution is replenished in time, and the applied voltage is adjusted to 15 kV, the receiving distance is 25 cm, and a cylindrical metal rotating receiving disk is used to receive the electrospinning. The rotating receiving speed is adjusted to 700 r / h. After 5 min, a blend of the three is obtained.

[0062] 3. Collect the obtained blended fiber membranes and vacuum dry them for 48 hours to remove residual solvent; 4. The obtained blended fiber membrane was dried in a vacuum drying oven for 48 hours to obtain the desired tissue repair material.

[0063] Test case 1. Scar severity assessment test To verify the efficacy of the tissue repair material prepared in Example 1 in reducing postoperative scar formation and promoting physiological repair, a rat abdominal wall defect model experiment was conducted. SPF-grade SD rats (male, 8 weeks old, weighing 250±20g) were purchased from the Beijing Vital River Laboratory Animal Center (License No.: SCXK2023-0005) and approved by the ethics committee (Approval No.: IACUC-2024-0032). The experimental group used the material from Example 1 (20×20mm², ethylene oxide sterilized), the positive control group used the commercially available absorbable anti-adhesion material Neoveil (Gunze Ltd., Japan), and the negative control group underwent only surgical suturing. A full-thickness rat abdominal wall defect model (15mm in diameter) was established, and after layered suturing, the test material was covered. Histological analysis was performed on postoperative days 7, 14, and 28.

[0064] H&E staining was used to observe morphological changes in scars, and histological examination of the formation of hypertrophic scars in wounds yielded the following results. Figure 2 Combining Figure 2 It can be seen that: 28 days post-surgery, the epidermal scar in the experimental group was smooth, the vascular density in the dermis was significantly increased, and no fibrosis was observed; in the control group, the epidermis was thickened and the collagen arrangement was disordered. Quantitative analysis using the scar elevation index (SEI) showed that the SEI value in the experimental group was 1.2±0.3, significantly lower than that in the Neoveil group (2.1±0.5) and the control group (3.5±0.7) (p<0.01).

[0065] Masson's trichrome staining was used to further evaluate collagen structure, and the scar elevation index (SEI) and epidermal thickness index (ETI) of hypertrophic scars were tested to obtain... Figure 3 Combining Figure 3 As can be seen, the collagen fibers in the experimental group were arranged regularly, similar to normal skin (score 4.5 / 5), while the Neoveil group and the blank group showed local cross-linking (score 3.0) and disordered deposition (score 1.8), respectively. Epidermal thickness index (ETI) analysis showed that the ETI value of the experimental group was 0.9±0.2, close to the level of normal tissue, while that of the blank group was 2.6±0.5, indicating that the material effectively inhibited excessive scar proliferation.

[0066] Combination Figure 2 and Figure 3 By evaluating the scar elevation index (SEI) and epidermal thickness index (ETI) at the wound site, it can be concluded that the degree of scarring in the experimental group using the tissue repair material prepared in Example 1 was significantly reduced compared to the control group, thus proving that the tissue repair material prepared in Example 1 has an excellent effect on promoting wound tissue repair and reconstruction.

[0067] 2. In vitro degradation test The tissue repair material prepared in Example 1 was cut into test pieces with dimensions of 20×20 mm². The test pieces were placed in a glass dish, and an in vitro degradation experiment was conducted to simulate the conditions of an in vivo liquid environment (temperature: 37℃, electrolyte and pH: 7.35~7.45). The degradation of the test pieces was observed, and the results were obtained. Figure 4 .

[0068] Combination Figure 4 As can be seen, the tissue repair material prepared in Example 1 can still completely retain its fibrous structure after a 7-day cycle, ensuring a long-term anti-adhesion effect after surgery, without the need for a second surgery to remove it (based on the time required for thoracic surgery).

[0069] By analogy, it can be concluded that the novel composite material has a reasonable degradation period after implantation: 1. It ensures that the barrier function can be maintained for a long time after the patient's surgery; 2. It meets the requirements of a normal recovery cycle and is basically degraded after recovery, thus maximizing safety.

[0070] In the description of the embodiments of the present invention, it should be noted that the terms "center," "longitudinal," "lateral," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing the embodiments of the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the embodiments of the present invention. In addition, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0071] In the description of the embodiments of the present invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "connected" and "linked" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium. Those skilled in the art can understand the specific meaning of the above terms in the embodiments of the present invention based on the specific circumstances.

[0072] In embodiments of the present invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature is in indirect contact with the second feature through an intermediate medium. Furthermore, "above," "on top of," and "over" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0073] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0074] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a polymeric tissue repair material, characterized in that, Includes the following steps: A first electrospinning solution, a second electrospinning solution, and a third electrospinning solution were prepared using a first tissue repair polymer, a second tissue repair polymer, and a third tissue repair polymer as solutes, respectively, wherein the degradation cycles of the first tissue repair polymer, the second tissue repair polymer, and the third tissue repair polymer are different from each other; The first electrospinning solution, the second electrospinning solution, and the third electrospinning solution are injected into a syringe, respectively. A pump propels the syringe to perform a first electrospinning, causing the first, second, and third electrospinning solutions injected into the syringe to spin first, second, and third filaments, respectively. A cylindrical metal rotating receiving disk receives the first, second, and third filaments, allowing the first, second, and third filaments to be blended and spun to obtain a first semi-finished product. The first electrospinning time is 3 to 5 minutes, the injection speed of the first electrospinning solution is 1 mL / h to 3 mL / h, the injection speed of the second electrospinning solution is 1 mL / h to 3 mL / h, the injection speed of the third electrospinning solution is 4 mL / h to 6 mL / h, the applied voltage is 10 kV to 20 kV, the receiving distance is 5 cm to 15 cm, and the rotation speed of the cylindrical metal rotating receiving disk is 700 r / h to 2000 r / h. After the first electrospinning is completed, the propulsion pump continues to advance the syringe for a second electrospinning, so that the first, second, and third electrospinning solutions injected into the syringe respectively spin the fourth, fifth, and sixth fibers. The cylindrical metal rotating receiving disk continues to receive the fourth, fifth, and sixth fibers, so that the fourth, fifth, and sixth fibers continue to be blended and spun to obtain a second semi-finished product. The second semi-finished product and the first semi-finished product form a blended fiber membrane. The second electrospinning time is 3 min to 5 min, the injection speed of the first electrospinning solution is 1 mL / h to 3 mL / h, the injection speed of the second electrospinning solution is 1 mL / h to 3 mL / h, the injection speed of the third electrospinning solution is 1 mL / h to 3 mL / h, the applied voltage is 15 kV to 25 kV, the receiving distance is 15 cm to 25 cm, and the rotation speed of the cylindrical metal rotating receiving disk is 700 r / h to 2000 r / h. The blended fiber membrane is dried to obtain the desired tissue repair material.

2. The preparation method of the polymer tissue repair material according to claim 1, characterized in that, The diameter of the first spun yarn is 2.5±0.5μm, the diameter of the second spun yarn is 3.0±0.5μm, and the diameter of the third spun yarn is 5.0±1.0μm; the porosity of the first semi-finished product is 70±5%, and the pore size of the first semi-finished product is 10-50μm.

3. The preparation method of the polymer tissue repair material according to claim 2, characterized in that, The diameter of the fourth spinning is 1.5±0.3μm, the diameter of the fifth spinning is 2.0±0.5μm, and the diameter of the sixth spinning is 4.0±1.0μm; the porosity of the second semi-finished product is 30±5%, and the pore size of the second semi-finished product is 50-200μm.

4. The preparation method of the polymer tissue repair material according to claim 3, characterized in that, The mass ratio of the first spinning, the second spinning, the third spinning, the fourth spinning, the fifth spinning, and the sixth spinning is (20-25):(15-20):(10-15):(15-20):(10-15):(5-10).

5. The method for preparing the polymeric tissue repair material according to claim 3, characterized in that, The second semi-finished product is stacked on the first semi-finished product to form a flat or tubular composite structure, wherein the inner diameter of the tubular structure is 3mm to 15mm.

6. The method for preparing the polymeric tissue repair material according to any one of claims 1 to 5, characterized in that, The mass concentration of the first electrospinning solution is 8%~12%, the mass concentration of the second electrospinning solution is 5%~9%, and the mass concentration of the third electrospinning solution is 15%~25%.

7. The method for preparing the polymeric tissue repair material according to claim 6, characterized in that, The first tissue repair polymer is polycaprolactone-polyethylene glycol-polycaprolactone, the second tissue repair polymer is polylactide, and the third tissue repair polymer is poly(ethylene glycol) block poly(γ-benzyl-L-methionine)amine.

8. The method for preparing the polymeric tissue repair material according to claim 7, characterized in that, The solvent of the first electrospinning solution is dioxane or dimethylformamide, the solvent of the second electrospinning solution is dioxane or dimethylformamide, and the solvent of the third electrospinning solution is dioxane or dimethylformamide.

9. The method for preparing the polymeric tissue repair material according to claim 6, characterized in that, The operation of drying the blended fiber membrane is as follows: after vacuum drying the blended fiber membrane to remove residual liquid, the blended fiber membrane is placed in a vacuum drying oven for 36h~48h again.

10. A polymeric tissue repair material, characterized in that, It is prepared by the preparation method of the polymer tissue repair material according to any one of claims 1 to 9.

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