A pet-hyaluronic acid double-layer composite tendon repair patch and a preparation method thereof

Abstract

The application belongs to the field of medical biomaterials and tissue engineering technology, and discloses a PET-hyaluronic acid double-layer composite tendon repair patch and a preparation method thereof. The patch comprises, from bottom to top, a bottom support layer, an interlayer interface and a surface active layer. The bottom support layer is a medical PET fabric layer or an electrospun base. The surface active layer is a hyaluronic acid nanofiber membrane layer formed by electrospinning. The interlayer interface is combined by covalent bonds or hydrogen bonds through surface activation treatment and in-situ deposition and crosslinking of hyaluronic acid nanofibers. The preparation method comprises the following steps: PET substrate cleaning, surface plasma or alkali activation; preparation of hyaluronic acid spinning solution; in-situ deposition of hyaluronic acid nanofibers on the activated PET base by electrospinning; crosslinking and curing; water washing, drying, cutting and sterilization. The patch has high mechanical support, biological activity and anti-adhesion performance, the interface is firmly combined, the process is simple, and the patch is suitable for tendon injury repair such as rotator cuff and Achilles tendon.

Description

Technical Field

[0001] This invention relates to the field of tendon repair patch technology, and more specifically, to a PET-hyaluronic acid bilayer composite tendon repair patch and its preparation method. Background Technology

[0002] Tendon injuries or ruptures are common in sports medicine, usually caused by sports injuries, traffic accidents, inflammation, aging, and degeneration. They often lead to pain, joint instability, and limited mobility, and in severe cases, loss of joint movement. Due to the tendon's own tissue structure and stress characteristics, its self-healing ability is poor, and external intervention is usually required.

[0003] Currently, the treatment of severe tendon injuries mainly relies on surgical intervention, including two main categories: direct suturing and tendon transplantation. However, for tendon injuries with defects larger than 3 cm, direct suturing is difficult to perform, requiring tendon transplantation. Although autologous tendon transplantation heals quickly and has less adhesion, the source is limited and the donor site is critical; allogeneic tendon transplantation faces limited sources and the risk of immune rejection; xenograft tendon transplantation is rarely used clinically, mainly due to immune rejection and mechanical performance issues.

[0004] Against this backdrop, artificial tendon repair patches have become a research hotspot. Current mainstream repair materials fall into two categories: one is non-absorbable synthetic patches, represented by PET and polylactic acid, which have strong mechanical properties but poor biocompatibility, lack of cell adhesion activity, and are prone to causing inflammation; the other is natural biomaterial patches, represented by hyaluronic acid (HA) and collagen, which have good biocompatibility, can promote cell regeneration, and prevent adhesion, but have weak wet mechanical properties, are easily degraded, and cannot withstand high tension. Simply combining the two presents core problems such as weak interfacial bonding, easy HA layer detachment, and uncontrolled swelling.

[0005] Therefore, developing a tendon repair patch that combines high mechanical support with good bioactivity, stable interfacial bonding, and controllable manufacturing process is of great clinical significance. Summary of the Invention

[0006] The purpose of this invention is to address the shortcomings of existing technologies by proposing a PET-hyaluronic acid bilayer composite tendon repair patch and its preparation method. This invention solves the technical problems of existing tendon repair patches being unable to simultaneously achieve high mechanical support and good bioactivity, as well as the weak interfacial bonding and easy delamination when different materials are combined.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] A PET-hyaluronic acid bilayer composite tendon repair patch includes a patch, wherein the patch comprises, from bottom to top, a bottom support layer, an interlayer interface, and a surface active layer;

[0009] The bottom support layer is a medical PET fabric layer or an electrospun substrate, and the surface active layer is a hyaluronic acid nanofiber (HA fiber) membrane layer formed by electrospun.

[0010] The interlayer interface is located between the bottom support layer and the surface active layer. The interlayer interface is formed by covalent bonds or hydrogen bonds through the surface activation treatment of the bottom support layer and the in-situ deposition and cross-linking of hyaluronic acid nanofibers in the surface active layer.

[0011] As a preferred embodiment, the thickness of the bottom support layer is 0.3-1.5 mm, the pore size is 80-200 μm, and the porosity is 60%-70%.

[0012] The tensile strength of the bottom support layer is ≥20 MPa, and the elastic modulus is 3-10 GPa.

[0013] As a preferred embodiment, the thickness of the surface active layer is 0.01-0.5 mm, the fiber diameter is 200-800 nm, the porosity is 70%-80%, and the degree of crosslinking is 30%-50%.

[0014] As a preferred embodiment, the bonding strength of the interlayer interface is ≥0.5 N / cm.

[0015] As a preferred embodiment, the patch has an overall thickness of 0.3-2 mm, a width of 5-60 mm, and a length of 10-100 mm.

[0016] This invention also provides a method for preparing the above-mentioned PET-hyaluronic acid bilayer composite tendon repair patch, comprising the following steps:

[0017] 1) The medical PET fabric or electrospun substrate used to form the underlying support layer is cleaned and surface activated to obtain an activated base layer;

[0018] 2) Prepare a hyaluronic acid electrospinning solution for forming the surface active layer;

[0019] 3) Using the activated PET substrate as a receiving device, hyaluronic acid nanofibers are deposited in situ on at least one surface of the activated PET substrate by electrospinning to form the surface active layer, and at the same time, an initial interface is formed between the bottom support layer and the surface active layer through in-situ composite.

[0020] 4) Immerse the composite structure obtained in step 3) in a crosslinking solution for crosslinking and curing treatment, so that the initial interface is transformed into the interlayer interface, and adjust the degree of crosslinking of the surface active layer to reach 30%-50%;

[0021] 5) The cross-linked composite structure is washed and purified, dried and shaped, cut and sealed, sterilized and packaged to obtain the finished patch.

[0022] As a preferred embodiment, the surface activation treatment in step 1) is plasma activation or alkaline activation;

[0023] The conditions for plasma activation are: Ar or O2 atmosphere, power 80-120 W, and processing time 3-5 min.

[0024] As a preferred embodiment, the hyaluronic acid electrospinning solution in step 2) is: hyaluronic acid concentration of 8%-12% w / v, and the solvent is a mixed solvent of deionized water and ethanol in a volume ratio of 7:3.

[0025] As a preferred embodiment, the electrospinning conditions in step 3) are: voltage 15-22 kV, receiving distance 12-18 cm, feed speed 0.5-1.0 mL / h, ambient temperature 25℃, and relative humidity 45%-55%.

[0026] As a preferred embodiment, the crosslinking solution in step 4) is a 0.1%–0.5% w / v genipin solution or a 1%–3% w / v ethylene glycol diglycidyl ether solution; the crosslinking conditions are room temperature treatment for 2–4 hours or treatment at 4°C overnight.

[0027] Compared with the prior art, the advantages of this invention are:

[0028] I. Synergistic effect of dual-layer structure: The bottom support layer provides high-strength mechanical support, while the surface active layer of hyaluronic acid nanofiber membrane provides bioactivity, anti-adhesion and regeneration promotion, thus achieving a synergistic balance between mechanical properties and bioactivity.

[0029] 2. High interfacial bonding strength: Plasma activation enhances the surface energy of the substrate, introduces active groups such as hydroxyl and carboxyl groups, and combines in-situ electrospinning deposition and cross-linking technology to form an interlayer interface with covalent or hydrogen bonds, achieving peel resistance, swelling resistance, and delamination resistance.

[0030] III. Controllable cross-linking technology: Low-toxicity cross-linking agents such as genipin or ethylene glycol diglycidyl ether are used, and the degree of cross-linking is controllable. The degradation cycle of the HA layer in vivo (8-24 weeks) matches the tendon regeneration cycle.

[0031] IV. Biomimetic Fiber Structure: Hyaluronic acid nanofibers mimic the structure of the natural extracellular matrix (ECM), guiding tendon cells to grow in a directional and orderly manner, accelerating tendon tissue regeneration and functional recovery.

[0032] V. Simple preparation process and scalable production: The process flow is clear, the parameters are controllable, the cost is low, and it is easy to achieve industrialization. Attached Figure Description

[0033] Figure 1 This is a schematic diagram of the structure of a double-layer composite patch;

[0034] Figure 2 This is a diagram showing the outline of a double-layer composite patch.

[0035] Figure 3 This is a flowchart illustrating the fabrication process of a double-layer composite tendon repair patch.

[0036] Explanation of the labels in the diagram:

[0037] 1. Bottom support layer; 2. Interlayer interface; 3. Surface active layer;

[0038] 10. Patches. Detailed Implementation

[0039] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0040] Example 1

[0041] I. Patch Structure

[0042] like Figure 1-2 As shown, this embodiment provides a PET-hyaluronic acid bilayer composite tendon repair patch 10, which includes, from bottom to top, a bottom support layer 1, an interlayer interface 2, and a surface active layer 3.

[0043] The bottom support layer 1 is made of medical-grade woven PET fabric with a thickness of 1.0 mm, a pore size of approximately 120 μm, and a porosity of 65%. This bottom support layer 1 has a tensile strength of 50.5 MPa and an elastic modulus of 7.8 GPa, and can provide mechanical support that matches that of natural tendons.

[0044] Surface active layer 3: This is a hyaluronic acid (HA) nanofiber membrane formed by electrospinning, with a thickness of 0.5 mm, an average fiber diameter of 450 nm, a porosity of 75%, and a cross-linking degree of 42%. This layer has a biomimetic extracellular matrix structure, which can promote tendon cell adhesion, proliferation, and directional growth, while also preventing postoperative adhesions.

[0045] Interlayer interface 2: Located between the bottom support layer 1 and the surface active layer 3, it is formed by covalent and hydrogen bonds through plasma activation treatment of the PET surface and in-situ deposition and cross-linking of HA nanofibers. The interfacial bonding strength was measured to be 1.2 N / cm in a T-type peel test. No peeling or delamination was observed after 1000 repeated tensile cycles, demonstrating excellent peel resistance and swelling resistance.

[0046] The patch 10 has an overall thickness of 1.5 mm, a width of 20 mm, and a length of 30 mm. It is flexible and can be sutured, making it suitable for tendon repair scenarios such as rotator cuff and Achilles tendon repair.

[0047] II. Preparation Method

[0048] like Figure 3 As shown, the preparation method of the patch in this embodiment includes the following steps:

[0049] 1. Raw material preparation

[0050] Bottom support layer 1: Medical-grade woven PET fabric, 1.0 mm thick, 120 μm pore size, 65% porosity;

[0051] Surface active layer 3: Medical-grade high molecular weight HA powder, molecular weight 1500 kDa;

[0052] Crosslinking agent: Genipin (purity ≥ 98%);

[0053] Reagents: acetone, 75% ethanol, PBS buffer (pH=7.4), deionized water.

[0054] 2. Substrate pretreatment

[0055] Cut the PET fabric to the appropriate size and immerse it in acetone, 75% ethanol and deionized water in sequence, ultrasonically cleaning each for 15 minutes to remove surface oil, slurry and impurities; after cleaning, place it in a 45℃ forced-air drying oven to dry for later use.

[0056] 3. Plasma activation on substrate surface

[0057] The dried PET fabric was activated using a low-temperature plasma treatment device; the treatment parameters were: Ar atmosphere, power 100 W, and treatment time 4 min.

[0058] After treatment, active groups such as hydroxyl (-OH) and carboxyl (-COOH) are introduced into the PET surface, and the contact angle is reduced from the original 120° to below 45°, significantly improving hydrophilicity and providing a good interfacial reaction basis for the subsequent in-situ deposition of HA fibers.

[0059] 4. Preparation of HA electrospinning solution

[0060] Weigh 1.0 g of HA powder and dissolve it in a mixed solvent of 7 mL of deionized water and 3 mL of anhydrous ethanol to prepare a 10% w / v HA solution. Stir magnetically at room temperature for 5 h until completely dissolved, then let stand for 1 h to remove bubbles before use.

[0061] 5. In-situ deposition of HA fibers (double-layer molding)

[0062] The activated PET fabric obtained in step 3 was used as the receiving substrate and fixed on the receiving roller of the electrospinning machine. The HA spinning solution prepared in step 4 was injected into the syringe, and the electrospinning parameters were set as follows: voltage 18 kV, receiving distance 15 cm, feed speed 0.8 mL / h, ambient temperature 25℃, and relative humidity 50%.

[0063] Under the above conditions, HA nanofibers are directly deposited on the surface of PET fabric, and the deposition time controls the fiber layer thickness to be about 0.5 mm, forming a PET substrate-HA fiber bilayer composite structure.

[0064] 6. Interlayer cross-linking curing

[0065] Preparation of cross-linking solution: 0.2% w / v genipin dissolved in PBS buffer (pH=7.4);

[0066] The composite patch obtained in step 5 is completely immersed in the crosslinking solution and crosslinked at room temperature for 3 hours. During the crosslinking process, a crosslinking network is formed between the HA fibers (the degree of crosslinking reaches 42%), and at the same time, it undergoes covalent or hydrogen bonding with the active groups (-OH, -COOH) on the PET surface to form a stable interlayer interface.

[0067] 7. Water washing and purification

[0068] After crosslinking is completed, the composite patch is removed and washed three times with PBS buffer for 30 minutes each time. Then it is rinsed with deionized water until the surface is no longer sticky, so as to completely remove residual crosslinking agent and uncrosslinked free HA.

[0069] 8. Shaping and drying

[0070] The cleaned composite patch was placed in a vacuum drying oven and vacuum dried at 40°C for 18 hours until constant weight was achieved, with the moisture content controlled below 0.05%. This process maintains the porous and flexible structure of the HA fiber and protects its bioactivity.

[0071] 9. Trim and seal the edges.

[0072] The dried patch is cut to a size of 20 mm × 30 mm and the edges are heat-sealed to prevent fraying of the PET fabric edges.

[0073] 10. Packaging, Sterilization and Analysis

[0074] After the patch is cut and sealed, it is placed in an aluminum foil bag with a Tyvek breathable layer, sterilized with ethylene oxide (EO), and then placed in a ventilated environment for thorough desorption to remove residual ethylene oxide.

[0075] 11. Aseptic vacuum packaging

[0076] The qualified patches are transferred to sterile aluminum foil bags and vacuum-sealed to obtain finished patches.

[0077] III. Verification of Technical Effects

[0078] The patch prepared in Example 1 was subjected to systematic performance testing, and the results are as follows:

[0079] (1) Mechanical properties

[0080] The tensile strength of the patch was 50.5 MPa, the elastic modulus was 7.8 GPa, and the elongation at break was 45% when tested using a universal testing machine. These results are significantly higher than those of a single HA membrane (tensile strength < 5 MPa) and are comparable to those of natural tendons (30-50 MPa).

[0081] (2) Biocompatibility

[0082] Cell adhesion: After tendon cells were seeded on the surface of the patch and cultured for 24 hours, the cell adhesion rate reached 92%, while that of an unmodified single PET patch was only 45%.

[0083] Cell proliferation: After 7 days of culture, the cell proliferation rate on the patch was 185% (with the initial seeded cell number as 100%), which was significantly higher than that of the single PET group, indicating that the HA active layer can effectively promote the growth and proliferation of tendon cells.

[0084] (3) Anti-adhesion properties (animal experiments)

[0085] Using a rabbit Achilles tendon repair model, adhesion scores were assessed 6 weeks post-surgery. In this embodiment, the patch group scored 1.2 points (mild adhesion, easily separable), while the single PET patch group scored 3.8 points (severe adhesion, difficult to separate, and accompanied by tissue damage).

[0086] (4) In vivo degradation and regeneration (animal experiments)

[0087] Degradation: The HA layer degrades by about 60% at 8 weeks post-surgery and is almost completely degraded at 16 weeks. The degradation cycle matches the tendon tissue’s own regeneration cycle.

[0088] Regeneration: 24 weeks post-surgery, tissue samples were taken from the repair site for histological observation. The results showed that the newly formed tendon tissue was orderly arranged, with dense collagen fibers that were regularly arranged along the stress direction. Mechanical testing indicated that the fracture strength of the repaired tendon recovered to 85% of that of a normal tendon.

[0089] The above results indicate that the PET-hyaluronic acid bilayer composite tendon repair patch prepared in Example 1 has excellent mechanical properties, biocompatibility, and regeneration ability, meeting the requirements for clinical use.

[0090] Example 2

[0091] I. Patch Structure

[0092] This embodiment is basically the same as Embodiment 1, except that the structural parameters are different:

[0093] Bottom support layer 1: PET woven fabric with a thickness of 0.5 mm, an average pore size of 95 μm, and a porosity of 62%.

[0094] Surface active layer 3: The HA fiber membrane has a thickness of 0.1 mm, a fiber diameter of approximately 300 nm, a porosity of 80%, and a degree of crosslinking of 35%.

[0095] Interlayer interface bonding strength 2: 0.9 N / cm.

[0096] II. Preparation Method

[0097] The difference from Example 1 is as follows:

[0098] Plasma activation conditions: O2 atmosphere, power 80 W, processing time 5 min.

[0099] HA spinning solution concentration: 8% w / v.

[0100] Electrospinning parameters: voltage 15 kV, receiving distance 12 cm, feed speed 0.5 mL / h.

[0101] Crosslinking solution: 1% w / v EGDE (ethylene glycol diglycidyl ether), crosslinked overnight at 4°C.

[0102] The remaining steps are the same as in Example 1.

[0103] III. Technical Effects

[0104] Tests showed that the tensile strength of the patch in this embodiment was 35.6 MPa, the elastic modulus was 4.2 GPa, the cell adhesion rate was 88% at 24 hours, the cell proliferation rate was 162% at 7 days, and the adhesion score was 1.5 at 6 weeks postoperatively. The patch exhibited good overall performance and is suitable for tendon repair in areas of moderate tension.

[0105] Example 3

[0106] I. Patch Structure

[0107] This embodiment is basically the same as Embodiment 1, except that the structural parameters are different:

[0108] Bottom support layer 1: PET electrospun nonwoven fabric, 1.5 mm thick, with an average pore size of 180 μm and a porosity of 68%.

[0109] Surface active layer 3: The HA fiber membrane has a thickness of 0.3 mm, a fiber diameter of approximately 700 nm, a porosity of 72%, and a degree of crosslinking of 48%.

[0110] Interlayer interface bonding strength: 2: 1.5 N / cm.

[0111] II. Preparation Method

[0112] The difference from Example 1 is as follows:

[0113] The PET substrate is electrospun PET nonwoven fabric.

[0114] HA spinning solution concentration: 12% w / v.

[0115] Electrospinning parameters: voltage 22 kV, receiving distance 18 cm, feed speed 1.0 mL / h.

[0116] Crosslinking solution: 0.5% w / v genipin, crosslinking at room temperature for 2 hours.

[0117] The remaining steps are the same as in Example 1.

[0118] III. Technical Effects

[0119] Testing showed that the patch in this embodiment had a tensile strength of 68.2 MPa, an elastic modulus of 9.5 GPa, a 24-hour cell adhesion rate of 95%, a 7-day cell proliferation rate of 198%, and an adhesion score of 1.0 at 6 weeks post-surgery. This patch exhibits high mechanical strength and is suitable for repairing high-tension areas (such as the Achilles tendon and patellar tendon).

[0120] Example 4

[0121] I. Patch Structure

[0122] This embodiment is basically the same as embodiment 1, except that the material and structure of the bottom support layer 1 are different:

[0123] The bottom support layer 1 is made of electrospun PET nanofiber substrate with a thickness of 0.8 mm, an average pore size of 150 μm, and a porosity of 85%. This bottom support layer has a tensile strength of 28.5 MPa and an elastic modulus of 4.5 GPa. Compared with woven PET fabrics, the electrospun substrate has a higher specific surface area and porosity, more closely resembling the structure of the natural extracellular matrix, which is beneficial for early cell invasion and tissue integration.

[0124] Surface active layer 3: The HA fiber membrane has a thickness of 0.4 mm, a fiber diameter of approximately 500 nm, a porosity of 78%, and a degree of crosslinking of 40%.

[0125] Interlayer interface 2: Covalent and hydrogen bonds are formed through plasma activation treatment of the PET electrospun substrate and in-situ deposition and crosslinking of HA nanofibers. The interfacial bonding strength was determined to be 1.1 N / cm by T-type peel test.

[0126] II. Preparation Method

[0127] The preparation method of the patch in this embodiment includes the following steps:

[0128] 1. Preparation of electrospun PET substrate:

[0129] PET particles were dissolved in a mixed solvent of trifluoroethanol and dichloromethane (volume ratio 1:1) to prepare a 15% w / v PET spinning solution.

[0130] A flat-panel receiver was used, and the electrospinning parameters were set as follows: voltage 20 kV, receiving distance 15 cm, feed speed 1.0 mL / h, ambient temperature 25℃, and relative humidity 45%.

[0131] Four hours after spinning, a PET nanofiber substrate with a thickness of about 0.8 mm and an average fiber diameter of about 600 nm was obtained.

[0132] The obtained PET electrospun substrate was dried in a vacuum drying oven at 45°C for 24 hours for later use.

[0133] 2. PET substrate surface activation treatment: The above-mentioned PET electrospun substrate was activated using a low-temperature plasma treatment instrument; the treatment parameters were: Ar atmosphere, power 100 W, treatment time 4 min.

[0134] 3. Preparation of HA electrospinning solution: Same as in Example 1, prepare a 10% w / v HA solution.

[0135] 4. In-situ deposition of HA fibers: Using the activated PET electrospinning substrate obtained in step 2 as the receiving substrate, it is fixed on the receiving roller of the electrospinning machine. Using the same HA spinning solution and electrospinning parameters as in step 4 (voltage 18 kV, receiving distance 15 cm, feed speed 0.8 mL / h), HA nanofibers are directly deposited on the surface of the PET substrate. The deposition time controls the fiber layer thickness to be approximately 0.4 mm.

[0136] 5. Interlayer crosslinking and curing: Prepare a 0.2% w / v genipin crosslinking solution, immerse the above composite structure completely in the crosslinking solution, and crosslink at room temperature for 3 hours.

[0137] 6. Washing and purification, shaping and drying, cutting and sealing, sterilization and packaging: Same as steps 7-11 in Example 1.

[0138] III. Technical Effects

[0139] Testing revealed that the tensile strength of the patch in this embodiment was 28.5 MPa, the elastic modulus was 4.5 GPa, and the elongation at break was 58%. Although the tensile strength was slightly lower than that of a woven PET fabric patch, it was still far higher than that of a single HA membrane, and it could meet the mechanical requirements of some tendon repair scenarios (such as finger flexor tendons and small animal tendons). The cell adhesion rate was 95% at 24 hours, thanks to the high specific surface area and biomimetic structure of the electrospun PET substrate; the cell proliferation rate was 192% at 7 days, and the adhesion score was 1.3 at 6 weeks post-operation; after 1000 repeated stretching cycles, there was no detachment or delamination between the HA layer and the PET substrate, and the interfacial bonding strength remained stable.

[0140] The results of this embodiment demonstrate that high-performance PET-hyaluronic acid bilayer composite tendon repair patches can also be prepared using an electrospun PET nanofiber substrate. Compared to woven PET fabrics, the electrospun substrate has a higher specific surface area, better cell infiltration ability, and better tissue integration performance, making it suitable for repair scenarios with high tissue integration requirements. Meanwhile, its mechanical properties still meet the needs of some tendon repairs.

[0141] Comparative Example 1

[0142] Using medical PET woven fabric of the same specifications as in Example 1, after cleaning and plasma activation, without HA fiber deposition and cross-linking treatment, it was directly cut, sealed, sterilized, and packaged. Tests showed that its tensile strength was 52.1 MPa, but the 24-hour cell adhesion rate was only 41%, and the adhesion score in animal experiments 6 weeks after surgery was 3.9, with no ability to promote regeneration.

[0143] Comparative Example 2

[0144] The difference from Example 1 is that the PET substrate was not subjected to plasma activation treatment, and the HA fibers were directly electrospun and deposited on the untreated PET surface without a cross-linking and curing step. Test results showed that the HA layer had extremely weak adhesion to the PET substrate, with an interfacial bonding strength of only 0.1 N / cm. After soaking in water for 2 hours, the HA layer swelled severely and detached from the PET surface in large pieces, making it unsuitable as an implant material.

[0145] By comparing Examples 1-4 with Comparative Examples 1-2, it can be seen that the present invention, through the combination of "substrate surface activation + HA in-situ deposition + cross-linking curing" technology, successfully achieves a strong bond between the PET or electrospun bottom layer and the HA surface layer, while endowing the patch with excellent mechanical properties and bioactivity, thus solving the core problems in the prior art.

[0146] The above description is merely a preferred embodiment of the present invention; however, the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and its improved concepts, should be covered within the scope of protection of the present invention.

Claims

1. A PET-hyaluronic acid bilayer composite tendon repair patch, comprising a patch (10) characterized in that, The patch (10) consists of a bottom support layer (1), an interlayer interface (2), and a surface active layer (3) from bottom to top. The bottom support layer (1) is a medical PET fabric layer or an electrospun substrate, and the surface active layer (3) is a hyaluronic acid nanofiber membrane layer formed by electrospun. The interlayer interface (2) is located between the bottom support layer (1) and the surface active layer (3). The interlayer interface (2) is formed by covalent bonds or hydrogen bonds through the surface activation treatment of the bottom support layer (1) and the in-situ deposition and cross-linking of hyaluronic acid nanofibers in the surface active layer (3).

2. The PET-hyaluronic acid bilayer composite tendon repair patch according to claim 1, characterized in that, The thickness of the bottom support layer (1) is 0.3-1.5 mm, the pore size is 80-200 μm, and the porosity is 60%-70%. The tensile strength of the bottom support layer (1) is ≥20 MPa and the elastic modulus is 3-10 GPa.

3. The PET-hyaluronic acid bilayer composite tendon repair patch according to claim 1, characterized in that, The surface active layer (3) has a thickness of 0.01-0.5 mm, a fiber diameter of 200-800 nm, a porosity of 70%-80%, and a crosslinking degree of 30%-50%.

4. The PET-hyaluronic acid bilayer composite tendon repair patch according to claim 1, characterized in that, The bonding strength of the interlayer interface (2) is ≥0.5 N / cm.

5. The PET-hyaluronic acid bilayer composite tendon repair patch according to claim 1, characterized in that, The patch (10) has an overall thickness of 0.3-2 mm, a width of 5-60 mm, and a length of 10-100 mm.

6. A method for preparing a PET-hyaluronic acid bilayer composite tendon repair patch according to any one of claims 1-5, characterized in that, Includes the following steps: 1) The medical PET fabric or electrospun substrate used to form the underlying support layer (1) is cleaned and surface activated to obtain an activated base layer; 2) Prepare a hyaluronic acid electrospinning solution for forming the surface active layer (3); 3) Using the activated PET substrate as a receiving device, hyaluronic acid nanofibers are deposited in situ on at least one surface of the activated PET substrate by electrospinning to form the surface active layer (3), and at the same time, an initial interface is formed between the bottom support layer (1) and the surface active layer (3) through in situ composite. 4) Immerse the composite structure obtained in step 3) in a crosslinking solution for crosslinking and curing treatment, so that the initial interface is transformed into the interlayer interface (2), and adjust the degree of crosslinking of the surface active layer (3) to reach 30%-50%; 5) The cross-linked composite structure is washed and purified, dried and shaped, cut and sealed, sterilized and packaged to obtain the finished patch (10).

7. The method for preparing a PET-hyaluronic acid bilayer composite tendon repair patch according to claim 6, characterized in that, The surface activation treatment in step 1) is plasma activation or alkaline activation; The conditions for plasma activation are: Ar or O2 atmosphere, power 80-120 W, and processing time 3-5 min.

8. The method for preparing a PET-hyaluronic acid bilayer composite tendon repair patch according to claim 6, characterized in that, The hyaluronic acid electrospinning solution mentioned in step 2) is: hyaluronic acid concentration of 8%-12% w / v, and solvent is a mixed solvent of deionized water and ethanol in a volume ratio of 7:

3.

9. The method for preparing a PET-hyaluronic acid bilayer composite tendon repair patch according to claim 6, characterized in that, The conditions for electrospinning described in step 3) are: voltage 15-22 kV, receiving distance 12-18 cm, feed speed 0.5-1.0 mL / h, ambient temperature 25℃, and relative humidity 45%-55%.

10. The method for preparing a PET-hyaluronic acid bilayer composite tendon repair patch according to claim 6, characterized in that, The crosslinking solution mentioned in step 4) is a 0.1%–0.5% w / v genipin solution or a 1%–3% w / v ethylene glycol diglycidyl ether solution; the crosslinking conditions are room temperature treatment for 2–4 hours or treatment at 4°C overnight.

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