Polyester biological patch capable of being used for aortic root enlargement and preparation therefor

Abstract

Disclosed in the present invention is a polyester biological patch capable of being used for aortic root enlargement. The polyester biological patch is a polyester fabric attached with a collagen fiber coating. The collagen fiber coating is formed by subjecting collagen fibers to a first chemical cross-linking and a second chemical cross-linking. The first chemical cross-linking involves chemically cross-linking the collagen fibers to obtain collagen fibers that have undergone the first chemical cross-linking. The second cross-linking involves attaching the collagen fibers that have undergone the first chemical cross-linking to the internal voids of the polyester fabric and the surface of the polyester fabric, thus forming the collagen fiber coating by means of cross-linking. Also disclosed in the present invention is a preparation method for the polyester biological patch. The polyester biological patch provided in the present invention features a stable coating that is not easily detached, low permeability, resistance to degradation, good biocompatibility, good compliance, and excellent suture strength.

Description

Polyester biological patch for aortic root enlargement and its preparation Technical Field

[0001] This invention belongs to the field of biomedical materials technology, and particularly relates to polyester biological patches that can be used for aortic root enlargement and their preparation. Background Technology

[0002] Patients with small aortic valves often encounter prosthesis-patient mismatch (PPM) when they need valve replacement. If left untreated, this can lead to "surgical stenosis," which is a new outflow tract obstruction caused by the implant. This not only affects the patient's postoperative cardiac function recovery but also has serious adverse effects on the valve's hemodynamic performance and durability.

[0003] Clinically, aortic root enlargement can be performed using the Manouguian procedure, Nicks procedure, Yang procedure, Rittenhouse procedure, Mavroudis procedure, and Konno-Rastan procedure. In recent years, the Yang procedure has attracted particular attention and is crucial for patients with valvular disease and small valve annulus due to various causes. It can provide patients with better hemodynamics and improve long-term treatment outcomes.

[0004] Clinical practice has proven that aortic root enlargement can effectively reduce the incidence of PPM (peripheral pulmonary embolism), but there is still debate and optimization regarding how to perform aortic root enlargement and what implant material to use. Currently, there is no polyester bio-patch specifically designed for aortic root enlargement. In clinical practice, doctors usually cut a piece from an artificial blood vessel for aortic root enlargement, but this type of patch often has the following problems:

[0005] (1) The patch is coated with a coating that prevents leakage and increases the rate of endothelialization. However, this coating cannot adapt to the high pulsating pressure at the aortic root and is prone to detachment. (2) It has poor biocompatibility and slow endothelialization. Failure to achieve rapid endothelialization can lead to hemolysis, thrombosis, and long-term local calcification. (3) The patch is relatively thick (>0.5 mm), resulting in insufficient surgical operability and compliance, and poor mechanical properties. (4) The anti-leakage effect is poor. (5) The patch is made of a polymer woven material with a collagen coating, and its anti-leakage effect needs further improvement. (6) It is prone to bacterial infection. Summary of the Invention

[0006] The polyester biopatch for aortic root expansion provided by this invention is obtained through two chemical cross-linking steps, including a first chemical cross-linking and a second chemical cross-linking. The first chemical cross-linking involves cross-linking collagen molecules or collagen fibers to obtain collagen fibers that have undergone the first chemical cross-linking. The second cross-linking involves attaching the collagen fibers that have undergone the first chemical cross-linking to the internal voids and surface of the polyester fabric, thereby forming a collagen fiber coating.

[0007] During the research process, the inventors unexpectedly discovered that the melting point of the collagen fiber coating and the melting point of the collagen fiber after the first chemical cross-linking need to meet a certain difference relationship. By optimizing and adjusting the difference in the change of the collagen melting point, the polyester bio-patch coating is stable, has good anti-leakage effect, fast endothelialization speed, is not easy to fall off, is not easy to degrade, has good biocompatibility, good compliance, and excellent mechanical properties.

[0008] Furthermore, this invention has found that by controlling the range of four key mechanical parameters—maximum tensile elongation, elastic deformation rate, maximum tensile force, and the value of elastic deformation rate relative to maximum tensile elongation—it is helpful to further improve the stability of the collagen fiber coating of polyester bio-patterns, resulting in better leak-proof performance of the polyester bio-patterns.

[0009] As one aspect of the present invention, a polyester biopatch for aortic root enlargement is disclosed, wherein the polyester biopatch is a polyester fabric with an attached collagen fiber coating; the collagen fiber coating is formed by a first chemical crosslinking and a second chemical crosslinking of collagen molecules or collagen fibers (pH 7.0); the first chemical crosslinking involves chemically crosslinking the collagen fibers to obtain first-crosslinked collagen fibers; the second crosslinking involves attaching the first-crosslinked collagen fibers to the internal voids and surface of the polyester fabric, thus forming the collagen fiber coating; the melting point of the first-crosslinked collagen fibers is 68.21-71.53℃, the melting point of the collagen fiber coating is 75.13-85.88℃, and the difference between the melting point of the collagen fiber coating and the melting point of the first-crosslinked collagen fibers is in the range of 6.68-14.35℃.

[0010] Preferably, the difference between the melting point of the collagen fiber coating and the melting point of the collagen fiber after the first chemical cross-linking is in the range of 10.04-12.36℃.

[0011] As a preferred option, the polyester bio-patch has a maximum tensile elongation range of 28-69%, an elastic deformation rate range of 13-39%, a maximum tensile force range of 18-45N, and an elastic deformation rate as a percentage of the maximum tensile elongation range of 19-93%.

[0012] Preferably, the elastic deformation rate is 47-79% of the maximum tensile elongation.

[0013] Preferably, the polyester fabric is a polyester fabric that has been pretreated with an alkaline solution, wherein the alkaline solution is a mixed alkaline solution containing 1% sodium carbonate and 0.5% Tween 20 and 0.5% sodium hydroxide solution.

[0014] Preferably, the polyester fabric is a polyester fabric that has been pre-exposed to ultraviolet light.

[0015] As another aspect of the invention, a method for preparing a polyester biological patch that can be used for aortic root enlargement is provided, comprising:

[0016] S1. Using animal-derived (preferably mammalian-derived) collagen as raw material and glutaraldehyde as a cross-linking agent, collagen fibers with a melting point of 68.21-71.53℃ are obtained through the first chemical cross-linking process.

[0017] S2. Spray the collagen fibers obtained from step S1 through the first chemical cross-linking onto the polyester fabric, and dry it to obtain a polyester fabric with adsorbed collagen fibers.

[0018] S3. Immerse the polyester fabric with adsorbed collagen fibers in a crosslinking agent solution to obtain a polyester fabric with adsorbed collagen fibers impregnated with a crosslinking agent; the crosslinking agent solution is a compound solution of N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, preferably compounded in a 1:1 mass ratio, with a concentration of 5-80 mg / mL;

[0019] S4. Immerse the polyester fabric with collagen fibers impregnated with crosslinking agent obtained in step S3 into a collagen fiber solution with 0.1-20 mg / mL of collagen fibers that have undergone the first chemical crosslinking, let it stand for more than 2 hours, and then dry it to obtain a polyester bio-patch with a collagen fiber coating. The melting point range of the collagen fiber coating is 75.13-85.88℃.

[0020] Preferably, in step S2, the spraying density of the collagen fibers that have undergone the first chemical cross-linking on the polyester fabric surface is 1-6 mg / cm³. 2 .

[0021] Preferably, in step S2, the polyester fabric is a polyester fabric that has undergone alkali pretreatment or ultraviolet irradiation pretreatment.

[0022] In a specific embodiment, the alkaline pretreatment includes:

[0023] ①Alkali treatment 1: Immerse the polyester fabric in a mixed alkaline solution of 1% sodium carbonate + 0.5% Tween 20 at 60℃ for 25-30 minutes. Then, repeatedly wash the fabric with ultrapure water preheated to 60℃ until the washing solution no longer has obvious foam. Dry it in an oven at 60℃.

[0024] ②Alkali treatment 2: Immerse the dried polyester fabric in a 0.5% sodium hydroxide solution preheated to 99℃ for 25-30 minutes, then wash repeatedly with purified water at room temperature until the pH of the washing solution is 6.0-7.0. Lay the polyester fabric out and dry it.

[0025] In a specific embodiment, the ultraviolet irradiation includes: exposing the polyester fabric to a wavelength of 312nm for 30-120 minutes at an energy range of 10-90J.

[0026] This invention provides an aortic root enlargement patch with a stable coating that can withstand the high pulsating pressure at the aortic root, is not easily detached, has good anti-leakage effect, is not easily degraded, has good biocompatibility, good compliance, and excellent mechanical properties, for use in aortic root enlargement surgery. Detailed Implementation

[0027] Unless otherwise stated, the parts referred to in this application are parts by mass, the proportions are mass ratios, and the percentages are mass percentages.

[0028] Based on the actual clinical application needs and considering the physiological environment of the aortic root, this invention provides an aortic root enlargement patch that can withstand the high pulsating pressure of the aortic root, with sutures that are not easy to fall off, excellent anti-leakage effect, fast endothelialization speed, stable coating, anti-degradation, good biocompatibility, excellent mechanical properties, and good compliance.

[0029] I. Preparation of Collagen Fibers

[0030] Step 1, Animal-derived tissue pretreatment: After scraping off the surface fat from fresh pig skin tissue, soak it in acetone solution at room temperature for 16 hours. Then, wash it 3-5 times with deionized water to remove excess acetone. Next, put the material into 2.0M NaOH solution and stir at room temperature for 16 hours. After the treatment, soak it in deionized water and wash the material until it is neutral.

[0031] Step 2: Preparation of crude collagen extract: The washed material was crushed and homogenized in 0.5M acetic acid. The homogenized tissue was then used for collagen extraction at a ratio of 20:1 (tissue weight / pepsin weight) under controlled temperature of 18℃ and stirred for 72 hours. The extract was centrifuged to collect the supernatant, stirred evenly, and then clarified and filtered to control the turbidity to less than 30, thus obtaining the crude collagen extract.

[0032] Step 3, Purification: Use a tangential flow filtration system to ultrafilter the crude collagen molecule extract, concentrate it to 3 mg / ml, and then dialyze it with 20 mM acetic acid solution. After dialyzing 20 times the volume, collagen molecules are obtained.

[0033] Step 4, Collagen Fibrosis: Take a certain volume of purified collagen molecules and add 1 / 10 volume of phosphate buffer (0.2M Na2HPO4:0.2M NaH2PO4 = 7:3, v:v). Mix well, adjust the pH to 7.0, and incubate at 30℃ for 6 hours to obtain collagen fibers.

[0034] The above four steps can be performed using any means disclosed in the existing technology, as long as the corresponding technical objective can be achieved.

[0035] II. Preparation of collagen fibers after the first chemical cross-linking

[0036] S1. First chemical cross-linking: Steps 1-4 are collagen fibers obtained from biological collagen. The collagen fibers obtained in steps 1-4 are added to glutaraldehyde aqueous solutions of different concentrations, mixed, stirred overnight at 30°C, centrifuged to collect the precipitate, and washed 2-3 times with pH 7.0 phosphate buffer to obtain collagen fibers that have undergone the first chemical cross-linking.

[0037] The concentration range of the glutaraldehyde aqueous solution is 0.003%-0.04%. The concentrations of the glutaraldehyde aqueous solution used in Examples 1-8 are shown in Table 1 below. The difference between Examples 1-8 lies in the different concentrations of the glutaraldehyde aqueous solution used.

[0038] The melting point (denoted as "melting point 1") of the collagen fibers obtained in Examples 1-8 after the first chemical cross-linking was determined by differential scanning calorimetry (DSC). Specifically, the collagen fibers obtained in Examples 1-8 after the first chemical cross-linking were transferred to the test aluminum crucible of the differential scanning calorimeter, sealed in the differential scanning calorimeter, and the temperature was increased at 10 K / min under a nitrogen atmosphere. The scanning measurement was performed under the conditions of a temperature increase range of 25-100 °C (the temperature range covers the melting point range of the substance).

[0039] Examples 1-8

[0040] The main differences between Examples 1-8 and the measured melting points are shown in Table 1 below:

[0041] Table 1: Main differences between Examples 1-8 and measured melting points 1

[0042] Table 1 shows that the melting point range of the collagen fibers obtained in Examples 1-8 after the first chemical cross-linking is 68.21-71.53℃.

[0043] III. Adhesion of collagen fibers to polyester fabric after the first chemical cross-linking

[0044] S2. Uniformly spray the collagen fibers obtained in step S1, which have undergone the first chemical cross-linking, onto the surface of the polyester fabric at a spraying density of 1-6 mg / cm³. 2 (i.e., 1-6 mg is evenly sprayed onto each square centimeter of polyester fabric). After spraying, the fabric is dried in an oven at 30-35℃ to obtain polyester fabric with adsorbed collagen fibers.

[0045] S3. Fully immerse the polyester fabric with adsorbed collagen fibers in the second crosslinking agent solution and let it stand at room temperature for 20 minutes to obtain a polyester fabric with adsorbed collagen fibers impregnated with the crosslinking agent. Preparation method of the second crosslinking agent solution: Weigh N-hydroxysuccinimide (NHS) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) in a centrifuge tube at a mass ratio of 1:1, add pH 7.2 phosphate (PBS) solution to obtain the crosslinking agent solution. The concentration range of NHS and EDC is 5-80 mg / mL.

[0046] S4. Second chemical cross-linking: The collagen fibers obtained in S3 after the first chemical cross-linking were prepared into a collagen fiber solution with a concentration of 0.1-20 mg / mL using a pH 7.2 phosphate (PBS) solution.

[0047] The polyester fabric containing collagen fibers and impregnated with a cross-linking agent is immersed in a collagen fiber solution of the same type as the intended collagen fibers to be coated, and left to stand at room temperature for more than 2 hours (preferably overnight). Then, it is thoroughly dried at 30-35°C. At this time, the collagen fibers that have undergone two chemical cross-linkings form a collagen fiber coating that exists in the internal pores and surface of the polyester fabric, resulting in a polyester biological patch that can be used for aortic root enlargement. The polyester biological patch is coated with a collagen fiber coating.

[0048] The melting point of the coating (denoted as "Melting Point 2") was determined by differential scanning calorimetry (DSC). Specifically, the polyester biopatch and polyester fabric obtained in step S4 were transferred to the test aluminum crucible of the differential scanning calorimeter, sealed in the DSC, and the temperature was increased at 10 K / min under a nitrogen atmosphere. The temperature range was 25℃-100℃ (covering the melting point range of the substance). The melting point of the coating is the melting point of the collagen fiber coating after removing the background peaks of the polyester fabric.

[0049] The polyester bio-patch with a collagen fiber coating is dried to obtain a polyester bio-patch. Specifically, the polyester bio-patch with a collagen fiber coating is immersed in 100% glycerin to fully replace the water molecules in the polyester fabric with the glycerin, resulting in a dried polyester bio-patch.

[0050] Using collagen fibers with different degrees of crosslinking obtained in Examples 1-8 that have undergone the first chemical crosslinking, the spraying density and drying temperature in step S2 are controlled, the concentration of the crosslinking agent solution in step S3 is controlled, and the concentration of the collagen fiber solution and drying temperature in step S4 are controlled, respectively, to conduct Examples 9-56.

[0051] Examples 9-56

[0052] Based on the adhesion of collagen fibers to polyester fabric after the first chemical cross-linking, the main differences between Examples 9-56, melting point 2, and the results of the difference between melting point 2 and melting point 1 are shown in Table 2 below:

[0053] Table 2: Key differences and relevant melting points of Examples 9-56

[0054] Table 2 shows that:

[0055] (1) The melting point 1 of the polyester patch obtained in Examples 9-14 using the collagen fiber coating prepared in Example 1 after the first chemical cross-linking is 68.21℃. The melting point 2 of the polyester patch coating obtained in Examples 9-14 is in the range of 72.28-80.86℃. The difference between melting point 2 and melting point 1 is 4.07-12.65℃.

[0056] (2) The melting point 1 of the polyester patch obtained in Examples 15-20 using the collagen fiber coating prepared in Example 2 after the first chemical cross-linking is 68.67℃, and the melting point 2 of the polyester patch coating obtained in Examples 15-20 is in the range of 77.32-81.03℃. The difference between melting point 2 and melting point 1 is 8.65-12.36℃.

[0057] (3) The melting point 1 of the polyester patch obtained in Examples 21-26 using the collagen fiber coating prepared in Example 3 after the first chemical cross-linking is 68.98℃, and the melting point 2 of the polyester patch coating obtained in Examples 21-26 is in the range of 71.61-81.60℃. The difference between melting point 2 and melting point 1 is 2.63-12.62℃.

[0058] (4) The melting point 1 of the polyester patch obtained in Examples 27-32 using the collagen fiber coating prepared in Example 4 after the first chemical cross-linking is 69.35℃, and the melting point 2 of the polyester patch coating obtained in Examples 27-32 is in the range of 75.07-81.78℃. The difference between melting point 2 and melting point 1 is 5.72-12.43℃.

[0059] (5) The polyester patches obtained in Examples 33-38 have a melting point 1 of 69.67°C using the collagen fiber coating prepared in Example 5 after the first chemical cross-linking. The melting point 2 of the polyester patch coatings obtained in Examples 27-32 ranges from 73.93 to 88.19°C. The difference between melting point 2 and melting point 1 is 4.26-18.52°C.

[0060] (6) The melting point 1 of the polyester patch obtained in Examples 39-44 using the collagen fiber coating prepared in Example 6 after the first chemical cross-linking is 70.33℃, and the melting point 2 of the polyester patch coating obtained in Examples 39-44 is in the range of 76.17-85.34℃. The difference between melting point 2 and melting point 1 is 5.84-15.01℃.

[0061] (7) The melting point 1 of the polyester patch obtained in Examples 45-50 using the collagen fiber coating prepared in Example 7 after the first chemical cross-linking is 70.98℃, and the melting point 2 of the polyester patch coating obtained in Examples 45-50 is in the range of 75.17-89.59℃. The difference between melting point 2 and melting point 1 is 4.19-18.61℃.

[0062] (8) The polyester patches obtained in Examples 51-56 were made from collagen fibers that underwent the first chemical cross-linking as prepared in Example 8. The melting point 1 of the coating was 71.53°C. The melting point 2 of the polyester patch coating obtained in Examples 51-56 ranged from 76.88 to 89.99°C. The difference between melting point 2 and melting point 1 was 5.35 to 18.46°C.

[0063] In summary, when the melting point 1 is 68.21-71.53℃, the melting point 2 of the polyester patch coating obtained in Examples 9-56 is 71.61-89.99℃, and the difference between melting point 2 and melting point 1 is 2.63-18.61℃.

[0064] Examples 9-56 show the coating peeling of the patches.

[0065] The collagen content before and after the pulsating flow experiment can directly reflect the stability of the coating. Infrared intensity is another indirect method for characterizing collagen content; comparing the intensity of the characteristic infrared peaks of collagen on the patch before and after pulsating flow can also indirectly reflect the stability of the coating.

[0066] The polyester bio-patterns prepared in Examples 9-56 above were subjected to pulsating flow experiments. Specifically, following ISO 5840 standards, polyester bio-patterns measuring 4 cm in length and 1 cm in width were sewn onto a pulsating flow platform. Under standard physiological conditions, after 90 days of pulsation, the collagen content and collagen infrared transmittance of the patches before and after the pulsating flow test were compared to evaluate the stability of the collagen fiber coating under pulsating flow. The test results are shown in Table 3.

[0067] Table 3: Changes in collagen coating content of patches obtained in Examples 9-56 before and after pulsation.

[0068] (1) As shown in Table 3, among the polyester patches obtained in Examples 9-14, the collagen content and collagen infrared transmittance of the polyester patch obtained in Example 9 before and after the coating pulsation flow changed significantly. Combined with Table 2, it can be seen that the melting point 2 of Example 9 is lower, and the difference between melting point 2 and melting point 1 is smaller.

[0069] Referring to Table 2, excluding the polyester patch obtained in Example 9, among the polyester patches obtained in Examples 9-14, when the melting point 1 is 68.21℃, the optimized range of melting point 2 is 75.13-80.86℃, and the optimized range of the difference between melting point 2 and melting point 1 is 6.92-12.65℃.

[0070] (2) As shown in Table 3, the changes in collagen content and collagen infrared transmittance before and after the pulsating flow of the polyester patch coating obtained in Examples 15-20 are relatively small.

[0071] Referring to Table 2, in the polyester patches obtained in Examples 15-20, when the melting point 1 is 68.67℃, the optimized range of the melting point 2 is 77.32-81.03℃, and the optimized range of the difference between the melting point 2 and the melting point 1 is 8.65-12.36℃.

[0072] (3) As shown in Table 3, among the polyester patches obtained in Examples 21-26, the changes in collagen content and collagen infrared transmittance before and after coating pulsation flow are relatively large for the polyester patch obtained in Example 25. Combined with Table 2, it can be seen that the melting point 2 of Example 25 is lower, and the difference between melting point 2 and melting point 1 is smaller.

[0073] Referring to Table 2, excluding the polyester patch obtained in Example 25, for the polyester patches obtained in Examples 21-26, when the melting point 1 is 68.98℃, the optimized range of melting point 2 is 78.22-81.60℃, and the optimized range of the difference between melting point 2 and melting point 1 is 9.24-12.62℃.

[0074] (4) As shown in Table 3, among the polyester patches obtained in Examples 27-32, the changes in collagen content and collagen infrared transmittance before and after the pulsating flow of the coating of the polyester patches obtained in Examples 27-31 are relatively small. By comparison, it can be found that the difference between melting point 2 and melting point 1 of the coating of the polyester patch obtained in Example 32 is relatively small.

[0075] Referring to Table 2, for the polyester patches obtained in Examples 27-32, when the melting point 1 is 69.35℃, the optimized range of melting point 2 is 78.52-81.78℃, and the optimized range of the difference between melting point 2 and melting point 1 is 9.17-12.43℃.

[0076] (5) As shown in Table 3, among the polyester patches obtained in Examples 33-38, the changes in collagen content and collagen infrared transmittance before and after pulsating flow of the polyester patch coatings obtained in Examples 33-34 and 36 are relatively small, indicating that the coatings are relatively stable. A comparison reveals that the differences between melting point 2 and melting point 1 of the polyester patch coatings obtained in Examples 35 and 37 are all extreme values, and the difference between melting point 2 and melting point 1 of the polyester patch obtained in Example 38 is close to the maximum extreme value.

[0077] Referring to Table 2, excluding Examples 35 and 37-38, the polyester patches obtained in Examples 33-38 have a melting point of 1 of 69.67℃, an optimized range of melting point 2 of 78.60-83.35℃, and an optimized range of the difference between melting point 2 and melting point 1 of 8.93-13.68℃.

[0078] (6) As shown in Table 3, among the polyester patches obtained in Examples 39-44, the coatings of the polyester patches obtained in Examples 39 and 42-43 are more stable. Combined with Table 2, the melting point 1 of the coating is 70.33℃, the optimized range of melting point 2 is 78.97-84.15℃, and the optimized range of the difference between melting point 2 and melting point 1 is 8.64-13.82℃.

[0079] (7) As shown in Table 3, among the polyester patches obtained in Examples 45-50, the coatings of the polyester patches obtained in Examples 46 and 49 are more stable. Combined with Table 2, it can be seen that when the melting point 1 of the coating is 70.98℃, the optimized range of melting point 2 is 77.66-84.14℃, and the optimized range of the difference between melting point 2 and melting point 1 is 6.68-13.16℃.

[0080] (8) As shown in Table 3, among the polyester patches obtained in Examples 51-56, the coatings of the polyester patches obtained in Examples 53 and 55 are more stable. Combined with Table 2, the melting point 1 of the coating is 71.53℃, the optimized range of melting point 2 is 81.57-85.88℃, and the optimized range of the difference between melting point 2 and melting point 1 is 10.04-14.35℃.

[0081] In summary, by comparing Tables 2 and 3, the inventors surprisingly discovered that when melting point 1 is 68.21-71.53℃, melting point 2 and the difference between melting point 2 and melting point 1 all need to meet certain values ​​to obtain a more stable coating on the polyester patch. Based on the conclusions of (1)-(8) above, it can be concluded that:

[0082] When the melting point 1 is 68.21-71.53℃ and the melting point 2 is 75.13-85.88℃, the probability of obtaining a stable polyester patch with a coating is high when the difference between the melting point 2 and the melting point 1 is 6.68-14.35℃.

[0083] When the melting point 1 is 68.21-71.53℃, and the difference between the melting point 2 and the melting point 1 is 10.04-12.36℃, the prepared polyester patch coating is very stable.

[0084] The following experiments were conducted on polyester bio-patterns obtained from Examples 11-12, 16, 22, 24, 28-29, 33-34, 39, 42, 46, 49, and 53 (hereinafter referred to as "14 optimized examples"), which met the range of 10.04-12.36℃ difference between melting point 2 and melting point 1.

[0085] Physical properties

[0086] (1) Appearance and thickness

[0087] Visual inspection of the polyester bio-patterns obtained from the 14 optimized embodiments showed that the patch surface was free of stains or foreign matter, tear marks, wear and particles.

[0088] Using a thickness gauge and general measuring tools, the thickness of the polyester bio-patch was found to be 0.35±0.15 mm in 14 optimized embodiments.

[0089] (2) Mechanical and overall water permeability test

[0090] Mechanical tests were conducted on polyester bio-patterns obtained from 14 optimized embodiments. The range of four mechanical parameters—maximum tensile elongation, elastic deformation rate, maximum tensile force, and the ratio of elastic deformation rate to maximum tensile elongation—was determined. The determination of maximum tensile elongation and maximum tensile force was based on existing literature (Li Chongchong, Liu Li, Wang Shuo, et al. Comparison of mechanical properties of allogeneic and animal-derived patches [J]. Beijing Biomedical Engineering, 2021.). The elastic deformation rate was determined using conventional methods in the art. Specifically, based on the tensile curve plotted when the maximum tensile elongation was measured, the elastic deformation rate of the aortic root enlargement patch was calculated based on the elastic deformation segment of the tensile curve.

[0091] Overall water permeability tests were conducted on the polyester bio-patterns obtained from 14 optimized embodiments, specifically according to YYT0500-2021. Circular patches with a diameter of 3 cm were cut, and the amount of water permeating from the patches within 1 minute under a pressure of 16 kPa was collected, and the overall water permeability was calculated. Overall water permeability is expressed as ml / (cm²). 2 ·min).

[0092] The experimental results of mechanical and overall water permeability tests are shown in Table 4:

[0093] Table 4: Mechanical and overall water permeability tests of polyester bio-patterns obtained from examples of coating stability.

[0094] As shown in the table above, the maximum tensile elongation of the polyester bio-patch obtained from the 14 optimized embodiments ranged from 28% to 69%, the elastic deformation rate ranged from 13% to 39%, the maximum tensile force ranged from 18% to 45N, and the elastic deformation rate as a percentage of the maximum tensile elongation ranged from 19% to 93%. The overall water permeability was 0.15-4.32 ml / (cm²). 2 ·min).

[0095] Referring to Table 2, the overall water permeability of Examples 12, 24, 28, 33-34, 39, 42, 46, and 53 is <1 ml / (cm²). 2 (min). At this point, the inventors were surprised to find that the elastic deformation rate of the polyester bio-patch accounted for 47-79% of the maximum tensile elongation.

[0096] Chemical properties

[0097] (1) Heavy metal content and trace elements

[0098] The test solution was prepared according to Method 3 of the preparation method of water extraction test solution in YY / T 1814-2022 "Surgical Implants - Synthetic Non-Absorbable Mesh Hernia Repair Mesh". The extraction ratio was 6 cm. 2 The extraction was performed at 70℃±2℃ for 24±2h, with the total sample area calculated from both sides. The prepared test solution was analyzed using inductively coupled plasma mass spectrometry (ICP-MS) according to General Chapter 0412 of the Pharmacopoeia of the People's Republic of China (2020 edition). Fourteen optimized examples yielded polyester biological patches. Experimental results showed that the total content of nickel, cobalt, copper, arsenic, mercury, lead, and chromium in the extract of the polyester biological patches obtained from the 14 optimized examples did not exceed 1 μg / mL; cadmium did not exceed 0.1 μg / mL; and the color of the extract did not exceed the concentration of lead standard control solution.

[0099] (2) Collagen content

[0100] The collagen content of polyester bio-patches obtained from 14 optimized examples was determined according to the method in Appendix A of YY / T 0954-2015 "Passive Surgical Implants - Type I Collagen Implants". The conversion factor (k) was 7.46, and the results met the requirements. The collagen content, calculated based on the area (both sides), was 0.5-3.0 mg / cm². 2 .

[0101] (3) Infrared absorption spectrum

[0102] Fourier transform infrared (FTIR) characterization was performed on polyester bio-patterns obtained from 14 optimized embodiments using an IRXross Fourier transform infrared spectrometer (Shimadzu). Infrared spectra were recorded at 4000–400 cm⁻¹. -1 The scanning speed is 4cm. -1 The characteristic peak wavelengths of the patch are in the range of 1647.72-1664.28 cm⁻¹. -1 Between 1548.22 and 1563.78 cm -1 between.

[0103] (4) Ethylene oxide residue

[0104] After measurement, the residual ethylene oxide content of the polyester bio-patterns obtained in the 14 optimized examples did not exceed 10 μg / g.

[0105] IV. Pretreatment 1: Alkali-treated polyester fabric

[0106] Preparation of Solution 1: Weigh 20g of sodium carbonate powder into 1990mL of sterile water for injection, then add 10g of Tween 20 to prepare a mixed alkaline solution of 1% sodium carbonate + 0.5% Tween 20 (referred to as "Solution 1"). Add a magnetic stir bar and stir thoroughly before use. Preparation of Solution 2: Weigh 10g of sodium hydroxide powder into a 2000mL glass bottle to prepare a 0.5% sodium hydroxide solution (referred to as Solution 2). Measure 2000mL of sterile water for injection into the glass bottle using a graduated cylinder. Add a magnetic stir bar and stir thoroughly before use.

[0107] ①Alkali treatment 1: Immerse the polyester fabric in solution 1 at 60℃ for 25-30 minutes, then repeatedly wash the fabric with ultrapure water preheated to 60℃ until the washing solution no longer produces obvious foam, and place it in an oven at 60℃ to dry.

[0108] ②Alkali treatment 2: Immerse the dried polyester fabric in solution 2 preheated to 99.0℃ for 25-30 minutes, then wash repeatedly with purified water at room temperature until the pH of the washing solution is 6.0-7.0 (using a pH meter for detection). Lay the polyester fabric out in a 15cm dish and dry it in an oven at 60℃ to obtain the alkali-treated polyester fabric.

[0109] Referring to section 3, the adhesion of collagen fibers after the first chemical cross-linking to polyester fabric was used to prepare polyester patches for Examples 57-66 using alkali-treated polyester fabric. The melting point of the coating (denoted as "melting point 3") was determined by DSC.

[0110] Examples 57-66

[0111] The difference between the melting point 2 and melting point 1 of the polyester bio-patterns obtained in the 14 optimized examples is within 10.04-12.36℃. Examples 57-66 are polyester bio-patterns prepared by alkali treatment of polyester fabric. The polyester bio-patterns obtained in Examples 57-66 are compared with 10 examples where the difference between the melting point 2 and melting point 1 is not within the range of 10.04-12.36℃. The main differences and detailed information on the measured melting points are shown in Table 5 below.

[0112] Table 5: Main differences between Examples 57-66 and measured melting points

[0113] As shown in Table 5, the difference between the melting point 3 and melting point 1 of the polyester bio-patch coating prepared using alkali-treated polyester fabric is closer to 10.04-12.36℃.

[0114] Examples 57-66 show the coating peeling of the patches.

[0115] The polyester bio-patterns prepared in Examples 57-66 above were subjected to pulsating flow experiments, and the test results are shown in Table 6:

[0116] Table 6: Changes in the coating of the patches obtained in Examples 57-66 before and after pulsation

[0117] As shown in the table above, polyester bio-patch prepared using alkali-treated polyester fabric exhibits less coating peeling and a more stable coating.

[0118] Examples 57-66 yielded mechanical and overall water permeability tests of the patch.

[0119] The polyester bio-patterns obtained in Examples 57-66 were subjected to overall water permeability tests, and the results are shown in Table 7.

[0120] Table 7: Experimental results of mechanical and overall water permeability tests of the patches obtained in Examples 57-66

[0121] As can be seen from the table above, the overall water permeability of the patches obtained in Examples 57-66 is relatively low.

[0122] Based on Tables 5-7, it can be concluded that the polyester fabric treated with alkali to obtain polyester bio-patch has a melting point difference of 10.66-12.21℃ (closer to 10.04-12.36℃), an elastic deformation rate of 50-76% of the maximum tensile elongation (within the range of 47-79%), high coating stability, and low overall water permeability.

[0123] V. Pretreatment 2: Ultraviolet irradiation of polyester fabric

[0124] Examples 67-71

[0125] A 312nm wavelength was selected, and the polyester fabric was exposed to UV light for 30-120 minutes at an energy range of 10-90J to obtain the UV-irradiated polyester fabric. Referring to section II, "Adhesion of Collagen Fibers to Polyester Fabric," the polyester patches of Examples 67-71 were prepared using the UV-irradiated polyester fabric. The melting point of the coating (denoted as "Melting Point 4") was determined by DSC.

[0126] Examples 67-71

[0127] Table 8: Key differences between Examples 67-71 and measured melting points

[0128] As shown in Table 8, the difference between the melting point 4 and melting point 1 of polyester bio-patch coating prepared from polyester fabric treated with ultraviolet irradiation is closer to 10.04-12.36℃.

[0129] Examples 67-71 show the coating peeling of the patches.

[0130] The polyester bio-patterns prepared in Examples 67-71 above were subjected to pulsating flow experiments, and the test results are shown in Table 9:

[0131] Table 9: Changes in the coating of the patches obtained in Examples 67-71 before and after pulsation.

[0132] As shown in the table above, the coating of the polyester bio-patterns obtained in Examples 67-71 peels off less and is more stable than the coating of the patches made from polyester fabric that has not been treated with ultraviolet radiation.

[0133] Examples 67-71 Mechanical and Overall Water Permeability Tests

[0134] The polyester bio-patterns obtained in Examples 67-71 were subjected to overall water permeability tests, and the results are shown in Table 10.

[0135] Table 10: Experimental results of mechanical and overall water permeability tests of the patches obtained in Examples 67-71

[0136] As can be seen from the table above, the overall water permeability of the patches obtained in Examples 67-71 is relatively low.

[0137] Based on Tables 8-10, it can be concluded that the polyester fabric treated with ultraviolet light to obtain polyester bio-patterns has a melting point 4 and melting point 1 difference range of 10.32-12.10℃ (closer to 10.04-12.36℃), an elastic deformation rate of 47-73% of the maximum tensile elongation (within the range of 47-79%), increased coating stability, and increased overall water permeability.

[0138] VI. Animal Experiments

[0139] Sheep have hearts and weights similar to humans, and their hemodynamic characteristics and laboratory indicators are also similar. Their coagulation system is similar to or slightly more prone to clotting than that of humans, making them a common animal model for heart valve and vascular replacement. Sheep are docile, easy to manage, less prone to postoperative infection, easier to control with long-term rearing, and have a high long-term survival rate. Therefore, sheep were chosen as the experimental animals for this experiment. Aortic replacement was performed on the same animal, along with aortic root enlargement surgery, to evaluate the safety and efficacy of the aortic root enlargement patch in vivo.

[0140] 1. Experimental Design and Grouping

[0141] The experiment was a single-arm experiment with a total of 6 male sheep of varying ages and weighing between 60-90 kg. The animals underwent open-chest surgery, and polyester biological patches were selected from 14 optimized examples, namely Examples 10, 15, and 21, to complete aortic replacement, while aortic root enlargement surgery was performed simultaneously.

[0142] The animals are housed in suspended stainless steel cages and fed at least twice a day. They drink municipal water from the city supply, with free access to the water. The housing conditions are: temperature 16-28℃, humidity 40-70% RH, ventilation frequency ≥8 times / hour, lighting 12 hours of light / 12 hours of dark cycle, and full-spectrum fluorescent lamps.

[0143] The facilities, cage quality, feed, water, and all environmental indicators for animal experiments meet the standards of GB 14925-2023 "Laboratory Animal Environment and Facilities," and animal management and feeding comply with the relevant provisions of the "Guidelines for the Management and Use of Laboratory Animals." The facilities and equipment will not cause accidental injury to the animals. Cages are regularly cleaned and disinfected to maintain cleanliness and comfort. Animal drinking and feeding devices are safe, reliable, convenient for feeding, and hygienic.

[0144] 2. Experimental Design

[0145] (1) Preoperative preparation

[0146] One week of preoperative acclimatization: 12-hour light-dark cycle, room temperature 22±6℃, humidity 40-70%, fasting period of 12-16 hours, but free access to water. The aortic valve annulus diameter of each animal was measured using CT scan before surgery.

[0147] Scopolamine hydrobromide injection (0.01 mg / kg, intramuscular injection) was administered to reduce respiratory secretions. Isoflurane was inhaled via face mask, and isoflurane was inserted through endotracheal intubation. Intravenous access was established, and a cardiac monitor was connected to monitor heart rate, blood pressure, and blood oxygen saturation.

[0148] (2) Surgical Procedure

[0149] Following standard procedures, the animal first underwent aortic root enlargement surgery, followed by repair using an aortic root patch.

[0150] a. Perform a transthoracic Doppler color ultrasound examination of the heart as required by routine examination procedures, and record the preoperative data;

[0151] b. The animal was placed in the right lateral decubitus position. The chest was routinely disinfected and a sterile sheet was applied. The left side of the chest was opened, the fourth rib was removed, and the whole body was heparinized to expose the heart.

[0152] c. Establish cardiopulmonary bypass as usual, place a left ventricular drainage tube, block the ascending aorta, and perfuse cold blood cardioplegic solution through the aortic root and / or the left and right coronary arteries. Cool the surface of the heart with ice chips.

[0153] d. Make an oblique incision in the ascending aorta, remove the aortic valve leaflets, measure the valve annulus diameter, extend the oblique incision in the aorta downward from the right side wall to the junction of the left and noncoronary valves, without cutting the left atrium, mitral valve annulus and the root of the anterior leaflet, then enlarge the aortic root with a patch, and then use a valve measuring device to measure the diameter of the widened aortic valve and record the widening data.

[0154] e. Select an artificial biological aortic valve of appropriate size and suture it to fix the aortic valve;

[0155] f. After the aorta is opened, defibrillation is performed to restart the cardiopulmonary bypass. Once the vital signs are stable, the cardiopulmonary bypass is stopped. Protamine sulfate is used to neutralize heparin, all perfusion tubes are removed, and the wound is hemostatically treated.

[0156] g. Transesophageal ultrasound examination of the function and hemodynamics of surgically implanted aortic valve;

[0157] h. After confirming that there is no active bleeding in the pleural cavity, place a drainage tube in the pleural cavity, close the chest layer by layer intermittently, and place the pleural drainage tube connected to the drainage bottle.

[0158] i. Remove the puncture sheaths from the jugular vein and femoral artery, and apply pressure to stop bleeding for at least 10 minutes;

[0159] j. Once the sheep can breathe independently, corneal radiation has recovered, and blood pressure and heart rate have stabilized, remove the endotracheal tube and observe it in a natural position for 30 minutes.

[0160] (3) Postoperative management

[0161] After successful surgery, the experimental animals were resuscitated and returned to the animal facility for continued observation and care. Food and water were provided regularly. Throughout the postoperative care period, the animals' condition was closely monitored, observing for signs of pain and administering appropriate analgesics.

[0162] Within 7 days post-surgery, administer ceftiofur sodium 5 mg / kg intramuscularly twice daily, and keep a record.

[0163] Heparin sodium was administered intravenously during the procedure at a dose of 1.5 mg / kg or 100-200 U / kg, maintaining ACT > 500 s.

[0164] On the day of surgery, warfarin sodium tablets plus aspirin were started at an initial dose of 5mg + 100mg. The warfarin sodium tablet dosage was adjusted according to the INR results to maintain the INR value within the range of 1.0-2.5. In case of bleeding or other complications, the anticoagulation regimen was adjusted according to the doctor's requirements.

[0165] In cases of bleeding or other complications, the anticoagulation regimen should be adjusted according to the doctor's instructions.

[0166] 3. Observation indicators

[0167] (1) General situation

[0168] Eat, mental state, lifestyle habits, bowel movements, and whether there is shortness of breath, decreased urination, or abnormal behavior.

[0169] (2) Blood test

[0170] This includes blood gas analysis, complete blood count, blood biochemistry, coagulation and immunology; and evaluation of hemolysis, inflammation and immune responses in animal blood after implantation of the device.

[0171] (3) Transthoracic ultrasound examination

[0172] Observe the valves and annulus for vegetations, abnormal blood flow, etc.; measure the left ventricular volume, aortic valve blood flow velocity and pressure gradient, and left ventricular ejection fraction; observe and record the size of each heart chamber, the degree of regurgitation of each valve, and the regurgitation in the experimental animals.

[0173] (4) CT

[0174] The diameter of the aortic valve annulus in animals was measured using CT scans before and after surgery.

[0175] (5) Gross anatomy and pathological examination

[0176] In this experiment, all animals that reached and did not reach the experimental endpoint underwent gross necropsy and pathological examination. Under general anesthesia, blood was drawn via femoral vein puncture (complete blood count, liver and kidney function tests); systemic heparinization was administered at 3 mg / kg (heparinization was to prevent blood clotting after sacrifice, which could be confused with thrombi formed within the artificial bio-heart valve); animals were euthanized by exsanguination under general anesthesia; the condition of the tissues surrounding the implanted artificial bio-heart valve and the presence of morphological changes, adhesions, fibrous cavities, etc., at the tissue junctions were observed and photographed; changes in the morphology of the artificial bio-heart valve leaflets, thrombus formation, and calcification were observed visually and photographed; if thrombi were present, the blood was recorded. The weight (wet weight) of the implant and its surface area as a percentage of the implant; observe the morphology of the prosthesis and record the deformation; collect the artificial bio-heart valve and surrounding tissue to make pathological sections and observe the pathological changes under a microscope: sample the artificial bio-heart valve and the surrounding 3mm area, fix it in 10% neutral formalin for 10-14 days, embed it in paraffin, section the tissue, and stain it with HE; organ anatomy: dissect organs such as the heart, lungs, spleen, liver, kidneys, and brain, first perform a gross examination, observe the condition of the surgical (chest) incision, whether there are infarcts and abnormal lesions, and take pictures and record them.

[0177] Table 11: Assessment and Observation Items

[0178] Notes: 1) Weight, sex, body temperature, heart rate, respiratory rate, etc. 2) Preoperative, intraoperative, and immediate postoperative data. 3) C-reactive protein. 4) Transvalvular pressure gradient, regurgitation, paravalvular leak, cardiac function; echocardiographic assessment at preoperative, intraoperative, and immediate postoperative follow-up points and at follow-up endpoints. Only transthoracic and transesophageal echocardiography were performed at follow-up points. Preoperative abdominal ultrasound was used to check liver and kidney function, and abnormal animal models were excluded. Abdominal ultrasound was used to check liver and kidney function before planned dissection. 5) Nine animals were included in each of the experimental and control groups. Three animals were harvested at 4 weeks for observation of gross conditions such as endometrialization and pathological examination; six animals were grossly dissected at 26 weeks after hematological data, ultrasound, and contrast imaging examinations. 6) Macroscopic observation: Pannus formation, tissue growth, thrombosis, calcium deposition, displacement or detachment of the prosthetic valve at the implantation site, accurate positioning related to flow direction (note instrument angularity, bending, and kinking), changes in the morphology and structural components of the prosthetic valve, endothelialization, etc. Histopathology: Inflammation, calcification, thrombosis, rejection reaction, other unexpected interactions with tissues, endothelialization, etc. Other: Examination of structural changes and calcification of the prosthetic valve, calcium content measurement. 7) Such as myocardial infarction, severe arrhythmia, embolism, prosthetic valve dysfunction.

[0179] (6) Processing and analysis of cardiac specimens

[0180] The left atrium and left ventricle were opened to observe the valve placement from the endocardial surface. Subsequently, tissue samples were taken from the ventricular wall and the periphery of the aortic valve, fresh or preserved at 4°C, and submitted for examination on the day of sacrifice at the test endpoint or within 24 hours of accidental death. A full organ examination was performed, focusing on changes on the valve surface and the presence of thromboembolism, infection, and necrosis in various organs. Routine light microscopic sampling was conducted, including samples from the left ventricle, left atrium, aorta, aortic root, and periphery of the aortic valve, as well as the artificial bio-heart valve.

[0181] Table 12: List of anatomical samples and microscopic examinations for the safety evaluation group

[0182] 4. Animal experiment results

[0183] (1) Polyester biological patches were used to perform aortic root enlargement on animals using Examples 10, 15 and 21 of the 14 optimized examples. No anastomotic bleeding or effusion occurred during or after the operation.

[0184] (2) During the period of survival and feeding, the animals were in good general condition, with normal body temperature, diet and excretion, good independent activity, and no abnormal behavior such as shortness of breath, oliguria, significant weight loss, fever, anorexia, or mania. They survived to the end without complications such as myocardial infarction, severe arrhythmia, embolism, or artificial valve dysfunction.

[0185] Complete blood count (including plasma free hemoglobin, white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cells, hemoglobin, hematocrit, and platelet count), blood biochemistry (total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, C-reactive protein, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, creatinine, uric acid, and blood urea nitrogen), and coagulation (including prothrombin time, thrombin time, and activated partial thromboplastin time) were all normal.

[0186] Electrolytes, liver and kidney function tests were almost entirely within the normal range during follow-up periods following cardiac radiofrequency ablation. The coagulation INR was approximately 1.0 both preoperatively and during follow-up. Complete blood cell count, morphology, and quality were normal. White blood cell, red blood cell, hemoglobin, and platelet counts showed overall stability with no significant abnormalities in any major blood routine indicators. No abnormalities were found in liver or kidney function; some values ​​were slightly above or below the reference range, but these were not clinically significant. Laboratory results without abnormalities before the procedure and before the endpoint were considered clinically significant.

[0187] The preferred embodiments of the present invention have been described in detail above. It should be understood that those skilled in the art can make numerous modifications and variations based on the concept of the present invention without creative effort. Therefore, all technical solutions that can be obtained by those skilled in the art based on the concept of the present invention through logical analysis, reasoning, or limited experimentation on the basis of existing technology should be within the scope of protection defined by the claims.

Claims

1. A polyester biological patch that can be used for aortic root enlargement, characterized in that, The polyester bio-patch is a polyester fabric with a collagen fiber coating; the collagen fiber coating is formed by cross-linking collagen fibers through a first chemical cross-linking and a second chemical cross-linking. The first chemical cross-linking is to chemically cross-link the collagen fibers to obtain collagen fibers that have undergone the first chemical cross-linking. The second cross-linking involves attaching the collagen fibers that have undergone the first chemical cross-linking to the internal pores and surface of the polyester fabric, thus forming a collagen fiber coating. The melting point of collagen fibers after the first chemical cross-linking is 68.21-71.53℃, and the melting point of collagen fiber coating is 75.13-85.88℃. The difference between the melting point of collagen fiber coating and the melting point of collagen fibers after the first chemical cross-linking is 6.68-14.35℃.

2. The polyester biological patch for aortic root enlargement according to claim 1, characterized in that, The difference between the melting point of the collagen fiber coating and the melting point of the collagen fiber after the first chemical cross-linking is 10.04-12.36℃.

3. The polyester biological patch for aortic root enlargement according to claim 1, characterized in that, The maximum tensile elongation range of polyester bio-patch is 28-69%, the elastic deformation rate range is 13-39%, the maximum tensile force range is 18-45N, and the elastic deformation rate as a percentage of the maximum tensile elongation ranges from 19-93%.

4. The polyester biological patch for aortic root enlargement according to claim 3, characterized in that, The elastic deformation rate accounts for 47-79% of the maximum tensile elongation.

5. The polyester biological patch for aortic root enlargement according to any one of claims 1-4, characterized in that, The polyester fabric is a polyester fabric that has been pre-treated with alkali.

6. The polyester biological patch for aortic root enlargement according to claim 5, characterized in that, The alkaline solution is a mixed alkaline solution containing 1% sodium carbonate and 0.5% Tween 20, and a 0.5% sodium hydroxide solution.

7. The polyester biological patch for aortic root enlargement according to any one of claims 1-4, characterized in that, The polyester fabric is a polyester fabric that has been pre-exposed to ultraviolet light.

8. A method for preparing a polyester biological patch that can be used for aortic root enlargement, characterized in that, include: S1. Using bio-derived collagen as raw material and glutaraldehyde as a cross-linking agent, collagen fibers with a melting point of 68.21-71.53℃ are obtained through the first chemical cross-linking process. S2. Spray the collagen fibers obtained from step S1 through the first chemical cross-linking onto the polyester fabric, and dry it to obtain a polyester fabric with adsorbed collagen fibers. S3. Immerse the polyester fabric with adsorbed collagen fibers in a crosslinking agent solution to obtain a polyester fabric with adsorbed collagen fibers impregnated with a crosslinking agent; the crosslinking agent solution is a compound solution of N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, preferably compounded in a 1:1 mass ratio, with a concentration of 5-80 mg / mL; S4. Immerse the polyester fabric with collagen fibers impregnated with crosslinking agent obtained in step S3 into a collagen fiber solution with 0.1-20 mg / mL of collagen fibers that have undergone the first chemical crosslinking, let it stand for more than 2 hours, and then dry it to obtain a polyester bio-patch with a collagen fiber coating. The melting point range of the collagen fiber coating is 75.13-85.88℃.

9. The method according to claim 8, characterized in that, In step S2, the spraying density of the collagen fibers that have undergone the first chemical cross-linking on the polyester fabric surface is 1-6 mg / cm³. 2 .

10. The method according to claim 8, characterized in that, It also includes alkali treatment or ultraviolet irradiation steps for pretreatment of polyester fabric; The alkaline treatment includes: ①Alkali treatment 1: Immerse the polyester fabric in a mixed alkaline solution containing 1% sodium carbonate and 0.5% Tween 20 at 60℃ for 25-30 minutes. Then, repeatedly wash the fabric with ultrapure water preheated to 60℃ until the washing solution no longer produces obvious foam. Dry it in an oven at 60℃. ②Alkali treatment 2: Immerse the dried polyester fabric in a 0.5% sodium hydroxide solution preheated to 99℃ for 25-30 minutes, then wash repeatedly with purified water at room temperature until the pH of the washing solution is 6.0-7.

0. Lay the polyester fabric out and dry it. The ultraviolet irradiation includes: exposing the polyester fabric to a wavelength of 312nm for 30-120 minutes at an energy range of 10-90J.

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