Polymer tissue repair material and preparation method thereof

Abstract

The invention discloses a tissue repair material and a preparation method thereof.The preparation method of the tissue repair material comprises the following steps that a first tissue repair polymer, a second tissue repair polymer and a third tissue repair polymer serve as solutes, and a first electrospinning solution, a second electrospinning solution and a third electrospinning solution are prepared, a blended fiber membrane is obtained after two times of electrospinning; and drying the blended fiber membrane to obtain the required tissue repair material. According to the preparation method of the tissue repair material, the first tissue repair polymer, the second tissue repair polymer and the third tissue repair polymer with different degradation periods are used, so that the prepared tissue repair material can be degraded step by step during use, and the degradation period of the tissue repair material is matched with a soft tissue repair period; therefore, the method can be matched with the multi-stage repairing process of the tissue (especially the soft tissue), provides whole-process protection for the repairing of the soft tissue, and has no extra burden.

Description

Technical Field

[0001] The present invention relates to the field of tissue repair, and in particular to a polymer tissue repair material and a preparation method thereof. Background Art

[0002] Soft tissue repair is an essential component of surgery, especially crucial for recovery after surgery or trauma. Currently, soft tissue repair materials on the market primarily include natural and synthetic polymers, metals, ceramics, and organic-inorganic composites. These materials play distinct roles in different stages of soft tissue repair, such as hemostasis, inflammation repair, plastic support, and proliferation.

[0003] Natural polymers, such as chitosan, hyaluronic acid, and collagen, are widely used in soft tissue repair due to their excellent biocompatibility and cell-friendliness. 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. Metal materials primarily provide structural support and promote healing, while ceramic materials play a role in assisting hard tissue repair due to their excellent biocompatibility and wear resistance.

[0004] However, existing technologies for soft tissue repair materials have limitations. Specifically, existing soft tissue repair materials are typically made from a single material using a simple interlaced fiber structure. This single material has a fixed degradation cycle and cannot accommodate the multi-stage repair process. Furthermore, this simple interlaced fiber structure cannot monitor cell growth, providing only a simple barrier and protective effect. Summary of the Invention

[0005] Based on this, it is necessary to provide a method for preparing a tissue repair material that can solve the above problems.

[0006] In addition, it is also necessary to provide a tissue repair material prepared by the above-mentioned method for preparing the tissue repair material.

[0007] A method for preparing a tissue repair material comprises the following steps: A first electrospinning solution, a second electrospinning solution and a third electrospinning solution are 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 respectively injected into the syringe, and 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 are injected into the syringe to respectively spin out the first spinning, the second spinning, and the third spinning, and the cylindrical metal rotating receiving disk receives the first spinning, the second spinning, and the third spinning, so that the first spinning, the second spinning, and the third spinning are blended and spun to obtain a first semi-finished product, wherein the first 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 4 mL / h to 6 mL / h, the loading voltage is 10 kV to 20 kV, the receiving distance is 5 cm to 15 cm, and the rotation receiving 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 is continued to be controlled to propel the syringe for a second electrospinning, so that the first electrospinning solution, the second electrospinning solution and the third electrospinning solution are injected into the syringe to respectively spin out the fourth spinning, the fifth spinning and the sixth spinning, and the cylindrical metal rotating receiving disk continues to receive the fourth spinning, the fifth spinning and the sixth spinning, so that the fourth spinning, the fifth spinning and the sixth spinning continue to be blended and spun to obtain a second semi-finished product, and the second semi-finished product and the first semi-finished product constitute a blended fiber membrane, wherein the second electrospinning time is 3min~5min, the injection speed of the first electrospinning solution is 1mL / h~3mL / h, the injection speed of the second electrospinning solution is 1mL / h~3mL / h, the injection speed of the third electrospinning solution is 1mL / h~3mL / h, the loading voltage is 15kV~25kV, the receiving distance is 15cm~25cm, and the rotation receiving speed of the cylindrical metal rotating receiving disk is 700r / h~2000r / h; The blended fiber membrane is dried to obtain the desired tissue repair material.

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

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

[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 sheet or tubular composite structure, wherein the inner diameter of the tubular structure is 3 mm to 15 mm.

[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: vacuum drying the blended fiber membrane to remove residual liquid, and then placing the blended fiber membrane in a vacuum drying oven to dry for 36 hours to 48 hours.

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

[0017] The preparation method of the tissue repair material of the present invention uses the first tissue repair polymer, the second tissue repair polymer, and the third tissue repair polymer with different degradation cycles, so that the prepared tissue repair material can be degraded step by step during use, so that its degradation cycle matches the soft tissue repair cycle, thereby matching the multi-stage repair process of tissue (especially soft tissue), providing full-process protection for soft tissue repair without additional burden.

[0018] In addition, 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 the two electrospinning processes. The high porosity (70%) of the first semi-finished product promotes the early attachment of tissue cells, and the low porosity (30%) of the second semi-finished product provides long-term mechanical support. The two synergistically match the soft tissue repair cycle, so that the prepared tissue repair material has a bionic fiber structure similar to the extracellular matrix, which can promote cell attachment and proliferation, and while playing a barrier and protective role, it can also effectively reduce postoperative inflammatory reactions.

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

[0020] Preferably, the third tissue repair polymer is poly(ethylene glycol)-block poly(γ-benzyl-L-methionine)amine, which is obtained by block-modifying these two materials with different glass transition temperatures. The glass transition temperature of PEG-MELG is 35.5±0.5°C as tested by differential scanning calorimetry (DSC), and it can achieve automatic curling and adhesion at human body temperature (36-38°C). The innovative glass transition temperature design achieves automatic adhesion in a human body temperature environment. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0022] in: Figure 1 The present invention is a flow chart of a method for preparing a tissue repair material according to one embodiment.

[0023] Figure 2 Graph showing the histological examination results of hypertrophic scar formation in the wound obtained in the test example.

[0024] Figure 3 Figure 3 is the SEI and ETI index diagram of hypertrophic scar obtained in the test case.

[0025] Figure 4 This is a diagram showing the in vitro degradation results of the tissue repair material prepared in Example 1. DETAILED DESCRIPTION

[0026] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0027] Combine Figure 1 The present invention discloses a method for preparing a tissue repair material according to an embodiment of the present invention, comprising the following steps: S10, preparing 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% 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%.

[0030] Generally speaking, the first tissue repair polymer, the second tissue repair polymer, and the third tissue repair polymer 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 acid-polyethylene glycol block copolymer (PELA), etc.

[0031] Specifically, this application breaks the limitation of using a single material. By studying the biocompatibility and degradation cycles of different materials, the authors 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. These three different materials are combined in a well-proportioned manner, resulting in a tissue repair material that degrades in stages during use, matching its degradation cycle with the soft tissue repair cycle. This allows the material to adapt to the multi-stage repair process of tissues, particularly soft tissue, providing comprehensive protection for soft tissue repair without any 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 is obtained by block-modifying these two materials with different glass transition temperatures. It can automatically curl at 36°C~38°C. The innovative glass transition temperature design enables automatic adhesion in a human body temperature environment.

[0033] Particularly, 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, respectively injecting the first electrospinning solution, the second electrospinning solution and the third electrospinning solution into the syringe, and 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 are injected into the syringe to respectively spin out the first spinning, the second spinning and the third spinning, and the cylindrical metal rotating receiving disk receives the first spinning, the second spinning and the third spinning, so that the first spinning, the second spinning and the third spinning are blended and spun to obtain a first semi-finished product.

[0036] Among them, the time of the first electrospinning is 3min~5min, the injection speed of the first electrospinning solution is 1mL / h~3mL / h, the injection speed of the second electrospinning solution is 1mL / h~3mL / h, the injection speed of the third electrospinning solution is 4mL / h~6mL / h, the loading voltage is 10kV~20kV, the receiving distance is 5cm~15cm, and the rotation receiving speed of the cylindrical metal rotating receiving disk is 700r / h~2000r / h.

[0037] Preferably, in this embodiment, high-voltage electrospinning technology is applied to prepare a first semi-finished fiber membrane with special porosity and fiber diameter by controlling parameters such as the pushing speed of the electrospinning solution, the loading 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, continue to control the propulsion pump to propel the syringe for the second electrospinning, so that the first electrospinning solution, the second electrospinning solution and the third electrospinning solution are injected into the syringe to spin out the fourth, fifth and sixth spinning respectively, and the cylindrical metal rotating receiving disk continues to receive the fourth, fifth and sixth spinning, so that the fourth, fifth and sixth spinning continue to be blended and spun to obtain a second semi-finished product, and the second semi-finished product and the first semi-finished product form a blended fiber membrane.

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

[0041] Preferably, in this embodiment, high-voltage electrospinning technology is applied to prepare a second semi-finished fiber membrane with special porosity and fiber diameter by controlling parameters such as the pushing speed of the electrospinning solution, the loading 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 sheet or tubular composite structure, wherein the inner diameter of the tubular structure is 3 mm to 15 mm.

[0045] Specifically, in this embodiment, in order to ultimately make the prepared tissue repair material have a structure similar to that of the extracellular matrix, the present application uses an electron scanning microscope to scan the extracellular matrix slices to obtain the structure of the extracellular matrix, and then adjusts the parameters in the two electrospinning processes to obtain fiber membranes with different porosity, pore size and fiber diameter (i.e., the first semi-finished product and the second semi-finished product), so that the prepared tissue repair material has a bionic fiber structure similar to the extracellular matrix, which can promote cell attachment and proliferation, and while playing a barrier and protective role, it can also effectively reduce postoperative inflammatory reactions.

[0046] S40, drying 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: vacuum drying the blended fiber membrane (48 hours) to remove residual liquid, and then placing the blended fiber membrane in a vacuum drying oven to dry it again for 36 hours to 48 hours.

[0048] The preparation method of 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, so that the prepared tissue repair material can be degraded step by step during use, so that its degradation cycle matches the soft tissue repair cycle, thereby matching the multi-stage repair process of tissue (especially soft tissue), providing full-process protection for soft tissue repair without additional burden.

[0049] In addition, the preparation method of the tissue repair material of the present invention obtains fiber membranes with different porosity, pore size and fiber diameter (i.e., the first semi-finished product and the second semi-finished product) by adjusting the parameters in the two electrospinning processes. The prepared tissue repair material has a bionic fiber structure similar to the extracellular matrix, which can promote cell attachment and proliferation, and while playing a barrier and protective role, it can also effectively reduce postoperative inflammatory reactions.

[0050] The present invention also discloses a tissue repair material prepared by the above-mentioned method for preparing the tissue repair material in one embodiment.

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

[0052] The following are specific examples.

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

[0054] Example 1 1. Dissolve polycaprolactone-polyethylene glycol-polycaprolactone (PCEC), polylactide (PLLA), and poly(ethylene glycol)-block poly(γ-benzyl-L-methionine)amine (PEG-MELG) in dioxane or dimethylformamide (DMF), respectively, and stir at room temperature for 18 hours to obtain three electrospinning solutions; the mass fraction of polycaprolactone-polyethylene glycol-polycaprolactone (PCEC) in the electrospinning solution is 10%, the mass fraction of polylactide (PLLA) is 7%, and the mass fraction of poly(ethylene glycol)-block poly(γ-benzyl-L-methionine)amine (PEG-MELG) is 20%. Inject the electrospinning solution into a syringe for use.

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

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

[0057] Example 2 1. Dissolve polycaprolactone-polyethylene glycol-polycaprolactone (PCEC), polylactide (PLLA), and poly(ethylene glycol)-block poly(γ-benzyl-L-methionine)amine (PEG-MELG) in dioxane or dimethylformamide (DMF), respectively, and stir at room temperature for 18 hours to obtain three electrospinning solutions; the mass fraction of polycaprolactone-polyethylene glycol-polycaprolactone (PCEC) in the electrospinning solution is 8%, the mass fraction of polylactide (PLLA) is 9%, and the mass fraction of poly(ethylene glycol)-block poly(γ-benzyl-L-methionine)amine (PEG-MELG) is 15%. Inject the electrospinning solution into a syringe for use.

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

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

[0060] Example 3 1. Dissolve polycaprolactone-polyethylene glycol-polycaprolactone (PCEC), polylactide (PLLA), and poly(ethylene glycol)-block poly(γ-benzyl-L-methionine)amine (PEG-MELG) in dioxane or dimethylformamide (DMF), respectively, and stir at room temperature for 18 hours to obtain three electrospinning solutions; the mass fraction of polycaprolactone-polyethylene glycol-polycaprolactone (PCEC) in the electrospinning solution is 12%, the mass fraction of polylactide (PLLA) is 5%, and the mass fraction of poly(ethylene glycol)-block poly(γ-benzyl-L-methionine)amine (PEG-MELG) is 25%. Inject the electrospinning solution into a syringe for use.

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

[0062] 3. Collect the obtained blended fiber membrane and vacuum dry it for 48 hours to remove the residual solvent; 4. Place the obtained blended fiber membrane in a vacuum drying oven and dry it for 48 hours to obtain the required tissue repair material.

[0063] Test Case 1. Scar degree 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 was conducted. SPF-grade Sprague-Dawley (male, 8 weeks old, weighing 250±20g) rats were purchased from the Beijing Weitonglihua Experimental Animal Center (license number: SCXK2023-0005) and approved by the Institutional Ethics Committee (approval number: IACUC-2024-0032). The experimental group used the material from Example 1 (20×20 mm², ethylene oxide sterilized). The positive control group used the commercially available absorbable anti-adhesion material Neoveil (Gunze Ltd., Japan). The negative control group underwent surgical closure alone. A full-thickness abdominal wall defect model (15 mm in diameter) was established in rats. The test material was then covered with the defect by layered closure. Histological analysis was performed on days 7, 14, and 28 after surgery.

[0064] H&E staining was used to observe the morphological changes of scars and the histological examination of hypertrophic scar formation in the wounds was performed. Figure 2 . Combined Figure 2 28 days after surgery, the experimental group had a smooth epidermal scar, significantly increased dermal vascular density, and no fibrous hyperplasia. In the blank group, the epidermis was thickened and collagen was disorganized. Quantitative analysis of the scar elevation index (SEI) showed that the experimental group had a SEI value of 1.2±0.3, significantly lower than that of the Neoveil group (2.1±0.5) and the blank group (3.5±0.7) (p<0.01).

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

[0066] Combine Figure 2 and Figure 3 By evaluating the scar elevation index (SEI) and epidermal thickness index (ETI) data at the wound site, it can be concluded that the scar degree of the experimental group using the tissue repair material prepared in Example 1 was significantly reduced compared with the control group, thereby proving that the tissue repair material prepared in Example 1 has an excellent effect in 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 of 20×20 mm² and placed in a glass dish. The product was subjected to an in vitro degradation test under the conditions of the in vivo liquid environment (temperature: 37°C, electrolyte and pH value: 7.35-7.45). The degradation of the test piece was observed and the results were obtained. Figure 4 .

[0068] Combine Figure 4 It can be seen that the tissue repair material prepared in Example 1 can still completely retain its fiber structure after a 7-day period, ensuring a long-term anti-adhesion effect after surgery and does not require a second operation to remove it (the test was conducted based on the time required for thoracic surgery).

[0069] Through conditional analogy, it can be seen that the new composite material has a reasonable degradation cycle after implantation in the body: 1. Ensure that the barrier effect can be maintained for a long time after the patient's operation; 2. It complies with the requirements of the normal recovery cycle and basically degrades after recovery, achieving maximum safety.

[0070] In the description of the embodiments of the present invention, it should be noted that the terms "center", "longitudinal", "lateral", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the accompanying drawings, and 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, be constructed and operate in a specific orientation, and therefore should not be understood as limiting the embodiments of the present invention. In addition, the terms "first", "second", and "third" are used for descriptive purposes only and should not be understood as indicating or implying relative importance.

[0071] In the description of the embodiments of the present invention, it should be noted that, unless otherwise specified or limited, the terms "connected" and "connection" should be understood in a broad sense. For example, they can refer to fixed connections, detachable connections, or integral connections; mechanical connections, electrical connections; and direct connections or indirect connections through an intermediary. Those skilled in the art will understand the specific meanings of the above terms in the embodiments of the present invention based on the specific circumstances.

[0072] In the embodiments of the present invention, unless otherwise expressly specified or limited, a first feature being "above" or "below" a second feature may mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediate medium. Furthermore, a first feature being "above," "above," or "above" a second feature may mean that the first feature is directly above or diagonally above the second feature, or simply means that the first feature is at a higher level than the second feature. A first feature being "below," "below," or "below" a second feature may mean that the first feature is directly below or diagonally below the second feature, or simply means that the first feature is at a lower level than the second feature.

[0073] In the description of this specification, the reference terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the embodiment of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0074] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A method for preparing a polymer tissue repair material, characterized in that: The steps include: A first electrospinning solution, a second electrospinning solution and a third electrospinning solution are 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 respectively injected into the syringe, and 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 are injected into the syringe to respectively spin out the first spinning, the second spinning, and the third spinning, and the cylindrical metal rotating receiving disk receives the first spinning, the second spinning, and the third spinning, so that the first spinning, the second spinning, and the third spinning are blended and spun to obtain a first semi-finished product, wherein the first 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 4 mL / h to 6 mL / h, the loading voltage is 10 kV to 20 kV, the receiving distance is 5 cm to 15 cm, and the rotation receiving 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 is continued to be controlled to propel the syringe for a second electrospinning, so that the first electrospinning solution, the second electrospinning solution and the third electrospinning solution are injected into the syringe to respectively spin out the fourth spinning, the fifth spinning and the sixth spinning, and the cylindrical metal rotating receiving disk continues to receive the fourth spinning, the fifth spinning and the sixth spinning, so that the fourth spinning, the fifth spinning and the sixth spinning continue to be blended and spun to obtain a second semi-finished product, and the second semi-finished product and the first semi-finished product constitute a blended fiber membrane, wherein the second electrospinning time is 3min~5min, the injection speed of the first electrospinning solution is 1mL / h~3mL / h, the injection speed of the second electrospinning solution is 1mL / h~3mL / h, the injection speed of the third electrospinning solution is 1mL / h~3mL / h, the loading voltage is 15kV~25kV, the receiving distance is 15cm~25cm, and the rotation receiving speed of the cylindrical metal rotating receiving disk is 700r / h~2000r / h; The blended fiber membrane is dried to obtain the desired tissue repair material.

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

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

4. The method for preparing a 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 a polymer 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 sheet or tubular composite structure, wherein the inner diameter of the tubular structure is 3 mm to 15 mm.

6. The method for preparing a polymer 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% 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%.

7. The method for preparing a polymer 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 a polymer 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 a polymer tissue repair material according to claim 6, characterized in that: The operation of drying the blended fiber membrane is as follows: vacuum drying the blended fiber membrane to remove residual liquid, and then placing the blended fiber membrane in a vacuum drying oven to dry for 36 hours to 48 hours.

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

Images