A plga-p4hb blended monofilament distributed synergistically degradable absorbable hernia patch

Abstract

The application discloses a kind of PLGA-P4HB blend monofilament distribution synergic degradable absorbable hernia repair patch, including the following parts: PLGA-P4HB composite substrate layer, P4HB coating and by PLGA-P4HB blend material constitutes edge reinforcing area.The hernia repair patch provided by the application, the ratio of P4HB and PLGA is reasonably controlled, the inherent difference of the degradation rate of PLGA and P4HB is used to construct gradient degradation structure, and the overall degradation period is controlled in 12-18 months, so as to match the whole cycle of tissue repair;Using melt blending spinning + warp knitting process to prepare mesh patch, the structural mechanical properties can be improved, and it is suitable for long-term stress of hernia repair;Meanwhile, using the characteristic that P4HB is not acidic degradation, buffering the inflammation risk caused by local accumulation of lactic acid and glycolic acid generated by PLGA degradation, improving biocompatibility, promoting tissue healing.Using fully absorbable two-component system, eliminate long-term foreign body reaction risk, realize the synchronization of patch degradation and tissue regeneration, so as to realize the smooth transition from physical repair to physiological repair.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, specifically to a PLGA-P4HB blended monofilament distribution synergistically degradable absorbable hernia patch. Background Technology

[0002] Abdominal wall hernia is a common surgical condition, primarily treated with hernia mesh implantation. The core function of the mesh is to provide mechanical support for the abdominal wall defect while promoting the ingrowth of surrounding tissues, thus achieving defect repair. Currently, commonly used hernia meshes are mainly divided into two categories: non-absorbable meshes and absorbable meshes. Non-absorbable meshes (such as polypropylene meshes) have stable mechanical properties, but long-term retention in the body can easily lead to complications such as foreign body reactions, infections, and adhesions. Absorbable meshes are mainly made from synthetic polymers such as polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), and poly4-hydroxybutyrate (P4HB). They can gradually degrade and be completely absorbed in the body, avoiding long-term foreign body irritation, but their mechanical properties are somewhat lacking. Therefore, combining different materials to create composite meshes, leveraging the advantages of different materials to improve the overall performance of the mesh, has become a research hotspot in the field of hernia repair.

[0003] Currently, composite patches are often manufactured by combining absorbable and non-absorbable materials. For example, CN102921048B discloses a partially absorbable fibrous membrane hernia patch, which uses non-degradable PVDF as the main component and adds a small amount of PLGA for electrospinning to prepare the hernia patch. PLGA is only used as an auxiliary absorbable component (accounting for 1%~20%), without P4HB, and the patch is partially absorbable (the main PVDF is non-absorbable). The permanent retention of PVDF provides mechanical support, while the short-term degradation of PLGA improves biocompatibility in the early stages of implantation. However, PVDF is a non-absorbable component, and its long-term retention in the body will continuously irritate surrounding tissues as a foreign body. After PLGA degrades, it can no longer maintain compatibility with the help of auxiliary components, resulting in reduced patch compatibility and significantly increasing the probability of postoperative infection and related complications. Especially in the case of infected abdominal wall defects, foreign body residue will exacerbate the inflammatory response, leading to repair failure.

[0004] Therefore, how to simultaneously improve the performance stability and biosafety of composite patches, while taking into account the ease of intraoperative operation and postoperative mechanical stability and tissue compatibility, has become a technical problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a PLGA-P4HB blended monofilament distribution synergistically degradable absorbable hernia patch.

[0006] This invention provides a PLGA-P4HB blended monofilament synergistically degradable absorbable hernia patch, comprising a patch body with a mesh structure, the patch body comprising the following parts: The PLGA-P4HB composite substrate layer includes a rough surface treated by plasma etching and a smooth and dense surface treated by low-temperature thermal planing. The rough surface is bonded to the surface layer of the abdominal wall. An edge reinforcement region is provided around the PLGA-P4HB composite substrate layer; The P4HB coating covers the smooth, dense surface of the PLGA-P4HB composite substrate layer, and its edges completely overlap with the edge reinforcement area. The PLGA-P4HB composite substrate layer and the edge reinforcement region are both composed of PLGA-P4HB blended monofilaments, and the mass ratio of PLGA to P4HB in the PLGA-P4HB blended monofilaments is 20:80~35:65. Preferably, the diameter of the PLGA-P4HB blended monofilament is 0.18~0.22mm; Preferably, the roughness of the rough surface is 1.0~2.0μm.

[0007] Furthermore, the PLGA-P4HB composite substrate layer has diamond-shaped braided holes with a pore size of 0.3~0.5mm; Preferably, the porosity of the PLGA-P4HB composite substrate layer is 75-85%.

[0008] Furthermore, the width of the edge reinforcement region is 4~6mm.

[0009] Furthermore, the thickness of the patch body is 0.3~0.4mm, and the thickness of the P4HB coating is 0.01~0.02mm.

[0010] Another aspect of the present invention provides a method for preparing the above-mentioned PLGA-P4HB blended monofilament synergistically degradable absorbable hernia patch, comprising the following steps: The weaving process involves the following steps using PLGA-P4HB blended monofilaments with a diameter of 0.18~0.22mm: (1) Molding of PLGA-P4HB composite substrate layer: The PLGA-P4HB composite substrate layer is obtained by using a plain weave with a weave density of 10~14 threads / inch. (2) Edge reinforcement zone forming: The needle pitch is increased by 15~25% and the yarn feed is increased by 20~30%. The edge of the PLGA-P4HB composite substrate layer is knitted with a variable warp flat method to obtain an edge reinforcement zone integrally formed with the PLGA-P4HB composite substrate layer. Double-sided modification includes the following steps: (1) Modification of the contact side of the structure: Plasma etching is performed on one side of the PLGA-P4HB composite substrate layer by argon gas to form the rough surface with a roughness of 1.0~2.0μm; (2) Abdominal side modification: The side of the PLGA-P4HB composite substrate layer opposite to the rough surface is subjected to low temperature heat flattening treatment at a temperature not exceeding 55°C to form the smooth and dense surface; Coating preparation: P4HB is prepared into a solution with a mass concentration of 5~7%, and coated on the smooth and dense surface and the edge reinforcement area located on the same side as the smooth and dense surface. After drying, the P4HB coating is formed.

[0011] Furthermore, in the braiding and forming step, the needle pitch used for braiding the PLGA-P4HB composite substrate layer is 1.15~1.27mm and the yarn feed is 450~550mm / loop, and the needle pitch used for braiding the edge reinforcement area is 0.86~1.08mm and the yarn feed is 540~715mm / loop. Preferably, the weaving and forming step further includes: After weaving is completed, the woven fabric is vacuum dried at 70℃ for 3-4 hours.

[0012] Furthermore, in the double-sided modification step, the plasma etching power is 100~150W and the time is 3~5min; Preferably, the temperature of the low-temperature heat leveling treatment is 45~55℃; Preferably, the double-sided modification step further includes: After the abdominal side modification is completed, it is soaked and cleaned with anhydrous ethanol for 5-10 minutes and then air-dried at room temperature.

[0013] Furthermore, in the coating preparation step, the method for preparing P4HB into a solution is as follows: Dissolve P4HB in benzyl benzoate at a mass concentration of 5-7%, stir to dissolve, and degas for 30 minutes; Preferably, in the coating preparation step, the drying method is as follows: After placing the patch body at room temperature for 1-2 hours, it is vacuum dried at 60°C for 2-3 hours, and then the temperature is raised to 80°C and vacuum dried for another 2 hours.

[0014] Furthermore, prior to the weaving and forming step, the following steps are also included: Preparation of PLGA-P4HB blended monofilaments: PLGA-P4HB blended materials were melt-spun at 165~170℃ using a melt spinning machine to obtain PLGA-P4HB blended monofilaments with a diameter of 0.18~0.22mm; Preferably, before the PLGA-P4HB blended monofilament preparation step, the following step is further included: Material pretreatment: Medical-grade PLGA particles and medical-grade P4HB particles are mixed at a mass ratio of 20:80 to 35:65 to obtain a uniform PLGA-P4HB blend. Preferably, the mixing conditions are 200~300 r / min and the time is 15~20 min.

[0015] Furthermore, following the coating preparation step, the following steps are also included: Post-processing of finished product: The patch body is freeze-dried under vacuum until the moisture content is ≤0.5%, thus obtaining the patch.

[0016] Preferably, the freeze-drying method is as follows: Dry for 8 hours at a temperature of -40℃ and a vacuum of -0.09MPa.

[0017] The technical effects of this invention are as follows: This invention discloses a PLGA-P4HB blended monofilament synergistic degradation absorbable hernia patch. It uses a safe and absorbable PLGA+P4HB composite material. By utilizing the inherent difference in degradation rates between the two materials, a gradient degradation structure is constructed. First, the P4HB coating located on the abdominal cavity side gradually degrades within 1-2 months, exposing the smooth and dense surface of the PLGA-P4HB composite substrate layer and preventing fluid accumulation. At the same time, the friction of the rough surface stimulates the abdominal wall tissue to produce chronic inflammation and exudate tissue fluid, promoting tissue encapsulation and ingrowth of the patch. During this period, the PLGA-P4HB composite substrate layer begins to slowly degrade (the overall degradation cycle is 12-18 months) until it is completely absorbed, which can extend the support cycle and thus match the entire cycle of tissue repair.

[0018] By blending P4HB with PLGA, the excellent and precisely controllable initial strength, manageable degradation cycle, and superior processing stability of PLGA ensure the uniformity of pore size and structural stability of the warp-knitted patch. The toughening effect of P4HB enhances the mechanical strength and toughness of the patch, resisting postoperative abdominal pressure impact. A melt-blended spinning + warp knitting process is used to prepare a mesh patch, improving structural mechanical properties and adapting it to the long-term stress of hernia repair. Simultaneously, the non-acidic degradation property of P4HB buffers the inflammatory risk caused by the local accumulation of lactic acid and glycolic acid generated during PLGA degradation, improving biocompatibility and promoting tissue healing. A fully absorbable two-component system is used to avoid the residue of non-degradable components and eliminate the risk of long-term foreign body reactions. The ratio of P4HB to PLGA is rationally controlled, leveraging the synergistic degradation and mechanical support of the two components to achieve simultaneous patch degradation and tissue regeneration, thus enabling a smooth transition from physical repair to physiological repair. Attached Figure Description

[0019] One or more embodiments are illustrated by way of example with reference to the accompanying drawings, and these illustrative examples are not intended to limit the embodiments. The term "illustrative" as used herein means "serving as an example, embodiment, or illustration." Any embodiment illustrated herein as "illustrative" is not necessarily to be construed as superior to or better than other embodiments.

[0020] Figure 1 This is a schematic diagram of the structure of the PLGA-P4HB blended monofilament distributed synergistic degradation absorbable hernia patch prepared in Example 1.

[0021] Figure 2 This is a partial cross-sectional view of the PLGA-P4HB blend monofilament distribution synergistic degradation absorbable hernia patch prepared in Example 1. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "comprising of," etc., will be understood to include the stated elements or components, and does not exclude other elements or other components.

[0023] Furthermore, to better illustrate the present invention, numerous specific details are set forth in the following detailed embodiments. Those skilled in the art will understand that the present invention can still be practiced even without certain specific details. In some embodiments, materials, elements, methods, and means well known to those skilled in the art are not described in detail in order to highlight the spirit of the invention.

[0024] Unless otherwise specified, the raw materials and equipment used in the following examples can be purchased commercially.

[0025] The PLGA used in this application, short for "polylactic acid-glycolic acid copolymer," is a commonly used absorbable medical polymer material. Its degradation rate can be controlled by the ratio of lactic acid (LA) to glycolic acid (GA). In the medical-grade PLGA selected in the following examples, the molar ratio of LA to GA is 75:25, and the degradation period is 12-18 months, which can balance degradation rate and mechanical properties.

[0026] The P4HB used in this application is short for "poly4-hydroxybutyrate", a commonly used absorbable medical polymer material with excellent flexibility and good biocompatibility. It degrades faster than PLGA and has been widely used in the field of implantable medical devices.

[0027] The hernia mesh provided in this application can be customized to meet clinical needs, with finished product specifications such as 5cm×7cm or 6cm×8cm for a single mesh. The mesh prepared in the following examples is 5cm×7cm in size.

[0028] Example 1 A PLGA-P4HB blended monofilament synergistically degradable absorbable hernia patch is prepared by the following method: S1: Material Pretreatment Medical-grade PLGA particles (LA:GA=75:25, molecular weight 100~150kDa) and medical-grade P4HB particles (molecular weight 80~120kDa) were selected and vacuum dried at 60℃ for 6 hours to avoid bubbles, pinholes and hydrolysis degradation of materials due to the presence of moisture during processing. The dried granules were mixed at a mass ratio of PLGA:P4HB=20:80 and mixed in a high-speed mixer at 200~300r / min for 15~20min to obtain a uniform PLGA-P4HB blend.

[0029] S2: Preparation of PLGA-P4HB blended monofilaments Using a melt spinning machine, the pretreated PLGA-P4HB blend raw material is added to the barrel. The barrel temperature is set as follows: feed section 155~160℃, melting section 165~170℃, and die head 160~165℃. After the raw material is completely melted (uniform melt state, no lumps or bubbles), it is extruded through a spinneret (spinneret orifice diameter 0.20~0.25mm, extrusion speed 5~8m / min). The extruded monofilament is immediately placed in a cooling water bath (water temperature 25~30℃) for cooling and shaping for 3~5 minutes, resulting in a preliminary PLGA / P4HB blend monofilament. The cooled and shaped monofilament is then placed in a stretching machine. The stretching temperature is set to 60~70℃ (below the raw material melting point to avoid monofilament melting and deformation), the stretching ratio is 3.0~3.5 times, and the stretching speed is 2~3m / min. After stretching, heat setting is performed (temperature 80℃, time 10 minutes) to obtain PLGA-P4HB blend monofilament with stable mechanical properties.

[0030] S3: Weaving and shaping Using the PLGA-P4HB blended monofilament prepared in S2, the following operations were performed on a warp knitting machine (gauge 20~22 needles / inch, corresponding needle pitch 1.15~1.27mm, yarn feed 450~550mm / loop): (1) Molding of PLGA-P4HB composite substrate layer: The PLGA-P4HB composite substrate layer is formed by using flat weaving with a finished weaving density of 10~14 threads / inch. It has regular rhomboid mesh with a pore size of 300~500μm and a porosity of 75%~85%. The pore walls are smooth and without sharp corners, which can achieve uniform mechanical support, good tissue ingrowth and smooth body fluid drainage, meeting the clinical needs of abdominal wall hernia repair. (2) Edge reinforcement zone formation: The needle pitch is increased by 15%–25% (needle pitch is 0.86~1.08mm), the yarn feed is increased by 20%–30% (540~715mm / loop), and the warp is changed to achieve integrated densification and thickening. The warp yarns are alternately padded on two or more adjacent needles to form loops, and the extension line spans two or more needle pitches to obtain an edge reinforcement zone integrally formed with the PLGA-P4HB composite substrate layer. By increasing the loop density and shortening the mesh aperture, the edge forms a near-dense micro-mesh structure, which significantly improves the edge's tear resistance, curl resistance and unraveling resistance while ensuring mesh connectivity.

[0031] After weaving, vacuum dry at 70℃ for 3-4 hours to eliminate internal stress and remove residual moisture.

[0032] S4: Double-sided modification The entire mesh is treated with double-sided differentiation, as follows: (1) Tissue contact side modification: Plasma etching is performed on one side of the PLGA-P4HB composite substrate layer by argon gas at a power of 100~150W and a time of 3~5min to form a rough surface with a roughness of Ra=1.0~2.0μm (to form a micro-uneven structure on the surface of the monofilament), thereby improving the tissue adhesion of the patch. (2) Cavity-side modification: The side of the PLGA-P4HB composite substrate layer opposite to the rough surface is subjected to low-temperature heat leveling treatment at a temperature of 45~55℃ to form a smooth and dense surface, avoiding liquid accumulation and organ adhesion. The surface stress of the monofilament is relaxed and the surface is leveled only when it is higher than the glass transition temperature Tg of the material, while it is much lower than the melting temperature to prevent pore collapse, deformation and damage to mechanical properties.

[0033] After double-sided treatment, soak and clean with anhydrous ethanol for 5-10 minutes to remove surface debris and impurities, and air dry at room temperature without damaging the monofilament structure and mechanical properties.

[0034] S5: Coating Preparation Dissolve P4HB in benzyl benzoate at a mass concentration of 5-7%, stir to dissolve, and degas for 30 minutes. Fix the surface-modified monofilament on a coating rack, and only partially dip-coat the peritoneal side for 10-20 seconds. After removal, place it in a fume hood and leave it at room temperature for 1-2 hours. Then, vacuum dry it at 60°C for 2-3 hours. After that, raise the temperature to 80°C and continue vacuum drying for 2 hours to remove the solvent and ensure that the residue meets the standard.

[0035] S6: Finished Product Post-Processing The patch body was dried at -40℃ and -0.09MPa for 8 hours until the moisture content was ≤0.5%; it was then sterilized with ethylene oxide (EO) to meet the sterility requirements of Class III implantable medical devices; after passing the tests on its mechanical properties, degradation properties, sterility level and solvent residue, it was vacuum sterile packaged for later use.

[0036] The patch prepared by the above method includes a patch body with a mesh structure, specifically comprising the following parts: The PLGA-P4HB composite substrate layer 1 has diamond-shaped braided holes with a pore size of 0.3~0.5mm, including a rough surface 11 (Ra=1.0~2.0μm) treated by plasma etching and a smooth and dense surface 12 treated by low temperature thermal flattening. The rough surface 11 is bonded to the surface layer of the abdominal wall. Edge reinforcement region 2, which surrounds the PLGA-P4HB composite substrate layer 1; P4HB coating 3, which is 0.015 mm thick, covers the smooth and dense surface 12 of the PLGA-P4HB composite substrate layer 1, and its edges completely overlap with the edge reinforcement area 2.

[0037] Example 2 A hernia repair patch is prepared using the same weaving process, pore size, and modification method as Example 1, except that the mass ratio of PLGA to P4HB in the PLGA-P4HB blended monofilament is changed to 28:72. The finished product includes the following components: The PLGA-P4HB composite substrate layer has diamond-shaped braided holes with a pore size of 0.3~0.5mm, including a rough surface (Ra=1.0~2.0μm) treated by plasma etching and a smooth and dense surface treated by low temperature thermal planing. The rough surface is bonded to the surface layer of the abdominal wall. An edge reinforcement region is provided around the PLGA-P4HB composite substrate layer; The P4HB coating, with a thickness of 0.015 mm, covers the smooth and dense surface of the PLGA-P4HB composite substrate layer, and its edges completely overlap with the edge reinforcement area.

[0038] Example 3 A hernia repair patch is prepared using the same weaving process, pore size, and modification method as Example 1, except that the mass ratio of PLGA to P4HB in the PLGA-P4HB blended monofilament is changed to 35:65. The finished product includes the following components: The PLGA-P4HB composite substrate layer has diamond-shaped braided holes with a pore size of 0.3~0.5mm, including a rough surface (Ra=1.0~2.0μm) treated by plasma etching and a smooth and dense surface treated by low temperature thermal planing. The rough surface is bonded to the surface layer of the abdominal wall. An edge reinforcement region is provided around the PLGA-P4HB composite substrate layer; The P4HB coating, with a thickness of 0.015 mm, covers the smooth and dense surface of the PLGA-P4HB composite substrate layer, and its edges completely overlap with the edge reinforcement area.

[0039] Comparative Example 1 A hernia repair patch is prepared using the same weaving process, pore size, and modification method as Example 1, except that the mass ratio of PLGA to P4HB in the PLGA-P4HB blended monofilament is changed to 10:90. The finished product includes the following components: The PLGA-P4HB composite substrate layer has diamond-shaped braided holes with a pore size of 0.3~0.5mm, including a rough surface (Ra=1.0~2.0μm) treated by plasma etching and a smooth and dense surface treated by low temperature thermal planing. The rough surface is bonded to the surface layer of the abdominal wall. An edge reinforcement region is provided around the PLGA-P4HB composite substrate layer; The P4HB coating, with a thickness of 0.015 mm, covers the smooth and dense surface of the PLGA-P4HB composite substrate layer, and its edges completely overlap with the edge reinforcement area.

[0040] Comparative Example 2 A hernia repair patch is prepared using the same weaving process, pore size, and modification method as Example 1, except that the mass ratio of PLGA to P4HB in the PLGA-P4HB blended monofilament is changed to 50:50. The finished product includes the following components: The PLGA-P4HB composite substrate layer has diamond-shaped braided holes with a pore size of 0.3~0.5mm, including a rough surface (Ra=1.0~2.0μm) treated by plasma etching and a smooth and dense surface treated by low temperature thermal planing. The rough surface is bonded to the surface layer of the abdominal wall. An edge reinforcement region is provided around the PLGA-P4HB composite substrate layer; The P4HB coating, with a thickness of 0.015 mm, covers the smooth and dense surface of the PLGA-P4HB composite substrate layer, and its edges completely overlap with the edge reinforcement area.

[0041] Comparative Example 3 A hernia repair patch, prepared using the same weaving process and modification method as in Example 1, differs from Example 1 in that the pore size of the PLGA-P4HB composite substrate layer is increased to 0.8~1.0 mm. The finished product includes the following components: The PLGA-P4HB composite substrate layer has diamond-shaped braided holes with a pore size of 0.8~1.0mm, including a rough surface (Ra=1.0~2.0μm) treated by plasma etching and a smooth and dense surface treated by low temperature thermal planing. The rough surface is bonded to the surface layer of the abdominal wall. An edge reinforcement region is provided around the PLGA-P4HB composite substrate layer; The P4HB coating, with a thickness of 0.015 mm, covers the smooth and dense surface of the PLGA-P4HB composite substrate layer, and its edges completely overlap with the edge reinforcement area.

[0042] Comparative Example 4 A hernia repair patch, prepared using the same weaving process and specifications as Example 1, differs from Example 1 in that the PLGA-P4HB composite substrate layer is not subjected to double-sided modification treatment. The finished product includes the following components: The PLGA-P4HB composite substrate layer has diamond-shaped braided holes with a pore size of 0.8~1.0mm; An edge reinforcement region is provided around the PLGA-P4HB composite substrate layer; The P4HB coating, with a thickness of 0.015 mm, covers the smooth and dense surface of the PLGA-P4HB composite substrate layer, and its edges completely overlap with the edge reinforcement area.

[0043] Comparative Example 5 A hernia repair patch, differing from Example 1 in that it does not include an edge reinforcement zone shaping step. The finished product comprises the following parts: The PLGA-P4HB composite substrate layer has diamond-shaped braided holes with a pore size of 0.8~1.0mm, including a rough surface (Ra=1.0~2.0μm) treated by plasma etching and a smooth and dense surface treated by low temperature thermal planing. The rough surface is bonded to the surface layer of the abdominal wall. A P4HB coating, 0.015 mm thick, is applied to the smooth, dense surface of the PLGA-P4HB composite substrate layer.

[0044] Comparative Example 6 A hernia repair patch is prepared using the same weaving process, hole shape and diameter, and modification method as Example 1. The difference from Example 1 is that PDO is used instead of P4HB, and the patch is mixed at a mass ratio of PDO:PLGA (LA:GA=75:25)=70:30. The finished product includes the following components: The PLGA-PDO composite substrate layer has diamond-shaped braided holes with a pore size of 0.8~1.0mm, including a rough surface (Ra=1.0~2.0μm) treated by plasma etching and a smooth and dense surface treated by low temperature thermal planing. The rough surface is bonded to the surface layer of the abdominal wall. PDO coating, which covers the smooth and dense surface of the PLGA-PDO composite substrate layer; A P4HB coating, 0.015 mm thick, is applied to the smooth, dense surface of the PLGA-P4HB composite substrate layer.

[0045] Experiment Example 1: Performance Testing of Different Patches Mechanical properties, degradation properties, and biocompatibility were tested on the patches prepared in Example 1 and Comparative Examples 1-6, respectively. Tensile strength was tested according to GB / T 3923.1, and flexural stiffness was tested according to ASTM F3260-25. A 0.1 mol / L PBS buffer (pH=7.4, 37℃) was used to simulate the in vivo degradation environment after surgery. Standard patch samples were immersed in this environment, and the tensile strength at break was tested initially and after 3 months of immersion. Tensile testing was performed using an electronic universal testing machine at a testing rate of 50 mm / min, with a sample width of 10 mm. Five parallel samples were tested in both the warp and weft directions, and the average value was taken after removing extreme values. The test results are shown in Table 1. Table 1. Test results of mechanical properties, degradation properties, and biocompatibility of each group of patches.

[0046] Test results show that the initial tensile strength of the patch provided in Example 1 is ≥30 N / cm, and after 3 months of simulated in vivo degradation, the tensile strength is still ≥20 N / cm, which can meet the abdominal wall support requirements 3 months after clinical surgery. It also has good biocompatibility and its performance is significantly better than that of Comparative Examples 1 to 5.

[0047] Experimental Example 2: Degradation Performance Test of Absorbable Hernia Membranes with Different Ratios of PLGA-P4HB Blended Monofilaments for Synergistic Degradation The patch prepared in Example 1 was tested for cytotoxicity, hemolysis, sensitization, and inflammatory response according to the methods provided in GB / T 16886.5-2017, GB / T 16886.4-2022, and GB / T 16886.10-2024, respectively. The test results are shown in Table 2.

[0048] Table 2. Biocompatibility test results of the patch in Example 1

[0049] Test results show that the patch provided in Example 1 of this application has good biocompatibility, is not cytotoxic or sensitizing, and fully meets the clinical safety requirements for medical patches.

[0050] Experimental Example 3: Degradation Performance Test of PLGA-P4HB Blended Monofilaments with Different Ratios for Synergistic Degradation of Absorbable Hernia Patches According to the method provided in Example 1, the degradation performance of the patches prepared in Examples 1-3 was tested, and the changes during the entire degradation process were recorded. The test results are shown in Table 3.

[0051] Table 3. Degradation performance test results of patches in Examples 1-3

[0052] Therefore, in the PLGA-P4HB blended monofilament distribution synergistic degradation absorbable hernia patch provided by the present invention, the degradation process of the patch can be adjusted by regulating the blending ratio of PLGA and P4HB, thereby changing the degradation cycle of the patch and thus being able to adapt to different patients and different treatment needs.

[0053] In summary, the PLGA-P4HB blended monofilament synergistic degradation absorbable hernia patch provided by this invention has the following advantages: 1. Degradation and tissue repair are precisely synchronized, significantly improving biosafety. The patch provided in this application uses a fully absorbable blend of PLGA and P4HB and a stepwise synergistic degradation coating of P4HB to construct a gradient degradation system. By adjusting the blending ratio gradient (PLGA:P4HB=20:80~35:65), the degradation cycle of the substrate is gradually changed (12~14 months, 14~16 months, 16~18 months). The degradation cycle is adjusted to match tissue repair, completely solving the problem of long-term foreign body retention, avoiding the hidden danger of asynchronous degradation and repair, reducing the risk of complications caused by long-term foreign body stimulation, adapting to complex clinical scenarios, and improving the versatility of the patch.

[0054] 2. Simultaneously promotes tissue ingrowth and prevents fluid accumulation, resulting in superior repair effects. This application designs a double-sided differentiated structure for the patch, and uses plasma etching technology to prepare the corresponding surfaces. The rough surface promotes tissue ingrowth through physical friction, while the abdominal side is smooth and dense, which can prevent fluid accumulation and eliminate aseptic inflammation, thereby reducing complications and improving repair stability.

[0055] 3. The coating adheres stably to the substrate, enhancing safety for clinical use. This application uses a P4HB coating that is homologous to the substrate. Through physical interlocking and intermolecular forces, it is bonded to the substrate without adhesive, which effectively improves the coating's bonding stability, avoids the risk of coating peeling, ensures safe use, and provides support for the overall performance of the patch.

[0056] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A PLGA-P4HB blended monofilament synergistically degradable absorbable hernia patch, characterized in that, The patch body includes a mesh structure and comprises the following parts: The PLGA-P4HB composite substrate layer includes a rough surface treated by plasma etching and a smooth and dense surface treated by low-temperature thermal planing. The rough surface is bonded to the surface layer of the abdominal wall. An edge reinforcement region is provided around the PLGA-P4HB composite substrate layer; The P4HB coating covers the smooth, dense surface of the PLGA-P4HB composite substrate layer, and its edges completely overlap with the edge reinforcement area. The PLGA-P4HB composite substrate layer and the edge reinforcement region are both composed of PLGA-P4HB blended monofilaments, and the mass ratio of PLGA to P4HB in the PLGA-P4HB blended monofilaments is 20:80~35:

65. Preferably, the diameter of the PLGA-P4HB blended monofilament is 0.18~0.22mm; Preferably, the roughness of the rough surface is 1.0~2.0μm.

2. The PLGA-P4HB blended monofilament synergistically degradable absorbable hernia patch according to claim 1, characterized in that, The PLGA-P4HB composite substrate layer has diamond-shaped braided holes with a pore size of 0.3~0.5mm; Preferably, the porosity of the PLGA-P4HB composite substrate layer is 75-85%.

3. The PLGA-P4HB blended monofilament synergistically degradable absorbable hernia patch according to claim 1, characterized in that, The width of the edge reinforcement zone is 4~6mm.

4. The PLGA-P4HB blended monofilament synergistically degradable absorbable hernia patch according to any one of claims 1 to 3, characterized in that, The thickness of the patch body is 0.3~0.4mm, and the thickness of the P4HB coating is 0.01~0.02mm.

5. A method for preparing a PLGA-P4HB blended monofilament synergistically degradable absorbable hernia patch according to any one of claims 1 to 4, characterized in that, Includes the following steps: The weaving process involves the following steps using PLGA-P4HB blended monofilaments with a diameter of 0.18~0.22mm: (1) Molding of PLGA-P4HB composite substrate layer: The PLGA-P4HB composite substrate layer is obtained by using a plain weave with a weave density of 10~14 threads / inch. (2) Edge reinforcement zone forming: The needle pitch is increased by 15~25% and the yarn feed is increased by 20~30%. The edge of the PLGA-P4HB composite substrate layer is knitted with a variable warp flat method to obtain an edge reinforcement zone integrally formed with the PLGA-P4HB composite substrate layer. Double-sided modification includes the following steps: (1) Modification of the contact side of the structure: Plasma etching is performed on one side of the PLGA-P4HB composite substrate layer by argon gas to form the rough surface with a roughness of 1.0~2.0μm; (2) Abdominal side modification: The side of the PLGA-P4HB composite substrate layer opposite to the rough surface is subjected to low temperature heat flattening treatment at a temperature not exceeding 55°C to form the smooth and dense surface; Coating preparation: P4HB is prepared into a solution with a mass concentration of 5~7%, and coated on the smooth and dense surface and the edge reinforcement area located on the same side as the smooth and dense surface. After drying, the P4HB coating is formed.

6. The method according to claim 5, characterized in that, In the braiding and forming step, the needle pitch used for braiding the PLGA-P4HB composite substrate layer is 1.15~1.27mm and the yarn feed is 450~550mm / loop; the needle pitch used for braiding the edge reinforcement area is 0.86~1.08mm and the yarn feed is 540~715mm / loop. Preferably, the weaving and forming step further includes: After weaving is completed, the woven fabric is vacuum dried at 70℃ for 3-4 hours.

7. The method according to claim 5, characterized in that, In the double-sided modification step, the plasma etching power is 100~150W and the time is 3~5min; Preferably, the temperature of the low-temperature heat leveling treatment is 45~55℃; Preferably, the double-sided modification step further includes: After the abdominal side modification is completed, it is soaked and cleaned with anhydrous ethanol for 5-10 minutes and then air-dried at room temperature.

8. The method according to claim 5, characterized in that, In the coating preparation step, the method for preparing P4HB into a solution is as follows: Dissolve P4HB in benzyl benzoate at a mass concentration of 5-7%, stir to dissolve, and degas for 30 minutes; Preferably, in the coating preparation step, the drying method is as follows: After placing the patch body at room temperature for 1-2 hours, it is vacuum dried at 60°C for 2-3 hours, and then the temperature is raised to 80°C and vacuum dried for another 2 hours.

9. The method according to any one of claims 5 to 8, characterized in that, Prior to the braiding and forming step, the following steps are also included: Preparation of PLGA-P4HB blended monofilaments: PLGA-P4HB blended materials were melt-spun at 165~170℃ using a melt spinning machine to obtain PLGA-P4HB blended monofilaments with a diameter of 0.18~0.22mm; Preferably, before the PLGA-P4HB blended monofilament preparation step, the following step is further included: Material pretreatment: Medical-grade PLGA particles and medical-grade P4HB particles are mixed at a mass ratio of 20:80 to 35:65 to obtain a uniform PLGA-P4HB blend. Preferably, the mixing conditions are 200~300 r / min and the time is 15~20 min.

10. The method according to any one of claims 5 to 8, characterized in that, Following the coating preparation step, the following steps are also included: Post-processing of finished product: The patch body is freeze-dried under vacuum until the moisture content is ≤0.5%, thus obtaining the patch; Preferably, the freeze-drying method is as follows: Dry for 8 hours at a temperature of -40℃ and a vacuum of -0.09MPa.

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