A tissue reinforcement material for thoracic and abdominal surgery and its preparation method

Abstract

This invention relates to the field of implantable medical device technology, specifically to a tissue reinforcement material for thoracic and abdominal surgery and its preparation method. The material uses a glycerol-lactic acid-glycolic acid hyperbranched polyester as a strength support layer, carrying pH-responsive antibacterial and anti-inflammatory microcapsules containing acylhydrazone bonds and chitosan-polylactic acid growth factor microcapsules. These are chemically grafted with 1,4-butanediol diglycidyl ether to form an integrated system, achieving a sequential synergistic effect of mechanical support, preferential release of antibacterial components under inflammatory conditions, and subsequent sustained release of growth factors. The material has a clear degradation pathway, producing biodegradable substances such as lactic acid and glycerol, with no toxic risks. It possesses both biocompatibility and safety, making it suitable for postoperative wound repair in procedures such as digestive tract reconstruction and tumor resection. It can significantly reduce infection rates, accelerate tissue regeneration, and prevent adhesions, providing an efficient repair solution for complex surgical procedures.

Description

Technical Field

[0001] This invention relates to the field of implantable medical device technology, and in particular to a tissue reinforcement material for thoracic and abdominal surgery and its preparation method. Background Technology

[0002] Postoperative tissue repair following thoracic and abdominal surgery faces multiple challenges, including insufficient mechanical support of the wound, high risk of postoperative infection, imbalance in inflammatory response regulation, and difficulty in constructing a tissue regeneration microenvironment. Currently widely used biodegradable materials such as polylactic acid (PLA), polyglycolic acid (PGA), and their copolymers (PLGA) provide short-term mechanical support, but their linear molecular structure leads to significant defects in their mechanical properties: tensile strength and elongation at break are negatively correlated, making it difficult to balance high strength with tissue adhesion. Studies have shown that the degradation rate of PLGA materials in body fluids does not match the tissue regeneration cycle; excessively rapid early degradation can lead to support failure, while excessive cross-linking prolongs degradation time and increases the risk of foreign body reactions. Furthermore, traditional polyester materials have strong surface hydrophobicity and generally low cell adhesion rates, severely limiting the targeted regeneration of the extracellular matrix.

[0003] Regarding functional improvements, existing technologies mostly employ physical blending methods to integrate drug components, but these suffer from burst release effects and uncontrollable release, failing to meet the need for sustained postoperative anti-infection. While pH-responsive carriers developed in recent years can achieve environment-triggered release, their single-response mechanism is insufficient to adapt to the dynamic changes in the postoperative microenvironment. Studies have indicated that local pH values ​​can drop to 5.5-6.5 during the inflammatory phase, while rising back to 7.2-7.4 during the repair phase. Existing carrier systems lack the ability to provide graded responses to different pH thresholds, leading to disordered release sequences of anti-inflammatory drugs and growth factors.

[0004] These technical bottlenecks severely restrict the effectiveness of tissue repair materials in complex and dynamic physiological environments. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and to propose a tissue reinforcement material for thoracic and abdominal surgery and its preparation method.

[0006] To achieve the above objectives, the present invention provides a method for preparing a tissue reinforcement material for thoracic and abdominal surgery, comprising the following steps:

[0007] S1. Under nitrogen protection, glycerol, lactic acid, glycolic acid, and p-toluenesulfonic acid are added to a reaction vessel, heated to 100-110℃, stirred for 30-60 min, then heated to 130-140℃ and reduced to 5-10 kPa, reacting for 4-6 h. After cooling to room temperature, the resulting solid is washed, dried, and added to dichloromethane, stirred for 20-30 min, then poured onto a glass plate. After heating to 35-40℃ to evaporate the solvent, the film is peeled off. The film is then washed and dried to obtain the strength support layer material. The chemical reaction diagram is as follows:

[0008] In formula (1), glycerol, as the branching core, copolymerizes with lactic acid and glycolic acid under the catalysis of p-toluenesulfonic acid to form a copolymer with a hyperbranched structure. Compared with traditional linear polymers, this hyperbranched copolymer can improve the elongation at break while meeting the tensile strength of the tissue reinforcement material, so that it will not detach due to tissue movement in complex wounds. At the same time, the hyperbranched structure brings more surface hydroxyl groups, which enhances the hydrophilicity of the material and improves the adhesion rate of tissue cells, allowing tissue cells to grow along the skeleton of the reinforcement material, providing a good environment for postoperative recovery.

[0009] S2. Oxalic acid dihydrazide and deionized water were added to a reaction vessel and heated to 70-90℃ with stirring. Glyceraldehyde was then added to ethanol to prepare a glyceraldehyde ethanol solution. The glyceraldehyde ethanol solution was added to the reaction vessel and stirred for 3-5 hours. After cooling to room temperature, the mixture was filtered. The resulting white solid was washed with an ethanol / water mixture and dried to obtain an acylhydrazone compound. The chemical reaction equation is as follows:

[0010] Formula (2), the product was characterized by H NMR. The acylhydrazone bond in the product is easily hydrolyzed and broken under acidic conditions. It then participates in the preparation of microcapsule wall material. Under the condition that the local tissue pH is acidic due to inflammation in the body, it is rapidly hydrolyzed and broken to release the antibacterial and anti-inflammatory agent in the core material, which can sterilize and reduce inflammation at the inflamed site and accelerate the healing of the wound.

[0011] S3. Add the acylhydrazone compound obtained in S2 to deionized water, adjust the pH to 9-11, add sodium periodate, stir the reaction at room temperature for 1-3 hours, filter to collect the solid, wash, and dry to obtain the carboxylated acylhydrazone compound. The chemical reaction equation is as follows:

[0012] Formula (3), under alkaline conditions, sodium periodate breaks the C-C bond in the vicinal diol structure of the acylhydrazone compound, oxidizes the hydroxyl group to an aldehyde group and further oxidizes it to a carboxyl group. The product was characterized by H NMR.

[0013] S4. Chitosan-polylactic acid copolymer and soybean lecithin were added to dichloromethane and stirred at room temperature for 20-40 min to obtain an oil phase. Growth factors were then added to deionized water to obtain an aqueous phase. The aqueous phase was poured into the oil phase, and genipin was added. The mixture was stirred at 1000-1500 rpm for 1.5-2.5 h. After drying and evaporating the solvent, the microcapsules were collected by centrifugation, washed, and freeze-dried to obtain growth factor microcapsules. Genipin was used as a crosslinking agent to improve the mechanical strength of the microcapsule wall material through crosslinking with chitosan. The chemical reaction diagram is shown below:

[0014] Equation (4);

[0015] S5. The carboxylated hydrazone compound obtained in S3 was added to a phosphate buffer solution, along with 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide. The mixture was stirred for 30-40 min, then chitosan-polylactic acid copolymer was added. The temperature was raised to 35-45℃, and the reaction was carried out for 3-5 h. After cooling to room temperature, the mixture was filtered, washed, and dried to obtain the chitosan-polylactic acid-hydrazone copolymer. The schematic diagram of the chemical reaction process is as follows:

[0016] Equation (5);

[0017] S6. Add the chitosan-polylactic acid-hydrazone copolymer and soybean lecithin obtained in S5 to dichloromethane and stir at room temperature for 20-40 min to obtain the oil phase. Then add the antibacterial and anti-inflammatory agent to deionized water and stir for 20-40 min to obtain the aqueous phase. Pour the aqueous phase into the oil phase and add genipin. Stir at 1000-1500 rpm for 1.5-2.5 h. After drying and evaporating the solvent, collect the microcapsules by centrifugation, wash them, and freeze-dry them to obtain the anti-inflammatory and antibacterial microcapsules. When facing the inflammation that may occur on the postoperative wound surface, the local tissue pH decreases due to inflammation, and the tissue becomes weakly acidic. This matches the hydrolysis and breakage of hydrazone bonds under acidic conditions, making the wall material of the anti-inflammatory and antibacterial microcapsules break faster than that of the growth factor microcapsules. The anti-inflammatory and antibacterial microcapsules release the antibacterial and anti-inflammatory agent in the core material first to kill bacteria and reduce inflammation. Then, they combine with the growth factor microcapsules to release growth factors, achieving the purpose of inflammation regulation and tissue regeneration.

[0018] S7. Immerse the strength support layer material obtained in S1 in a borax buffer solution containing 1,4-butanediol diglycidyl ether, heat to 40-45℃, and shake for 1-2 hours. Then wash with deionized water, add to the borax buffer solution, and then add the growth factor microcapsules obtained in S4 and the anti-inflammatory and antibacterial microcapsules obtained in S6. Heat to 35-45℃ and shake for 1-2 hours. After washing and drying, the product is used to obtain a tissue reinforcement material for thoracic and abdominal surgery.

[0019] Preferably, in S1, glycerol, lactic acid, glycolic acid, p-toluenesulfonic acid and dichloromethane are in a weight ratio of 0.1-0.2:2-3:2-3:0.005-0.01:20-30.

[0020] Preferably, in S2, the weight ratio of oxalic acid dihydrazide, glyceraldehyde, deionized water and ethanol is 1:1:8-12:3-7, and the ethanol / water mixed solution refers to the mixture of ethanol and water in a weight ratio of 3:7.

[0021] Preferably, in S3, the acylhydrazone compound, sodium periodate, and deionized water are in a weight ratio of 1:1:8-12.

[0022] Preferably, in S4, the chitosan-polylactic acid copolymer, soybean lecithin, growth factor, genipin, dichloromethane and deionized water are in the following weight ratios: 2-5:0.5-2:0.01-0.1:0.02-0.2:100:20-50.

[0023] Preferably, the growth factor in S4 is fibroblast growth factor (bFGF).

[0024] Preferably, in S5, the carboxylated hydrazone compound, chitosan-polylactic acid copolymer, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide and phosphate buffer solution are in a weight ratio of 1:5-10:0.05-0.07:0.05-0.07:80-120.

[0025] Preferably, the pH of the phosphate buffer solution in S5 is 7.4.

[0026] Preferably, in S6, the chitosan-polylactic acid-hydrazone copolymer, soybean lecithin, antibacterial and anti-inflammatory agent, genipin, dichloromethane and deionized water are in a weight ratio of 2-5:0.5-2:0.1-0.15:0.02-0.2:100:20-50.

[0027] Preferably, the antibacterial and anti-inflammatory agent in S6 refers to vancomycin and dexamethasone mixed in a weight ratio of 1:1.

[0028] Preferably, the two types of microcapsules mentioned above in this invention are prepared by solvent evaporation method, using chitosan-polylactic acid copolymer or modified copolymer containing acylhydrazone bonds as wall material, soybean lecithin as emulsifier, dichloromethane as oil phase solvent, and deionized water as aqueous phase to dissolve growth factors or antibacterial and anti-inflammatory agents. The wall material and soybean lecithin are dissolved in dichloromethane to form an oil phase, and the core material is dissolved in water to form an aqueous phase. The aqueous phase is poured into the oil phase under high-speed stirring, and genipin crosslinking agent is added to form a stable W / O primary emulsion. Subsequently, dichloromethane is removed by evaporation, allowing the wall material to deposit and encapsulate the aqueous phase droplets. After centrifugation, collection, washing, and freeze-drying, microcapsules with uniform particle size are obtained.

[0029] Preferably, in S7, the strength support layer material, borax buffer containing 1,4-butanediol diglycidyl ether, borax buffer, growth factor microcapsules, and anti-inflammatory and antibacterial microcapsules are in a weight ratio of 1:10-20:10-20:0.01-0.03:0.02-0.05.

[0030] Preferably, the content of 1,4-butanediol diglycidyl ether in the borax buffer solution containing 1,4-butanediol diglycidyl ether in S7 is 8-15 wt%.

[0031] Preferably, the pH of the borax buffer solution in S7 is 9.0.

[0032] Furthermore, the present invention also provides a tissue strengthening material for thoracic and abdominal surgery, prepared by the above-mentioned method, for postoperative tissue repair and strengthening in the thoracic and abdominal cavities. It provides mechanical support through a strength support layer material, and combines the sequential release of growth factor microcapsules and anti-inflammatory and antibacterial microcapsules to achieve integrated treatment of postoperative infection prevention, inflammation regulation and tissue regeneration. It is especially suitable for digestive tract reconstruction, wound repair and adhesion prevention after tumor resection.

[0033] The beneficial effects of this invention are:

[0034] 1. This invention constructs a three-dimensional hyperbranched polyester network using glycerol as the branching core. Its unique molecular entanglement and branch slippage characteristics endow the material with both high strength and high toughness, enabling it to withstand the dynamic mechanical loads of complex thoracic and abdominal surgical wounds and preventing material tearing or detachment due to tissue movement. Simultaneously, the hydroxyl groups enriched on the hyperbranched structure significantly enhance the material's hydrophilicity, adsorbing extracellular matrix proteins through hydrogen bonding, providing a highly efficient adhesion interface for fibroblasts, promoting orderly cell growth along the material's framework, and creating a microenvironment conducive to tissue regeneration. This solves the problems of insufficient hydrophilicity and low cell adhesion rates of traditional linear polymers.

[0035] 2. Based on the acid-sensitive properties of acylhydrazone bonds, this invention utilizes anti-inflammatory and antibacterial microcapsule wall materials that rapidly hydrolyze and break down in the acidic environment of the inflammatory site, preferentially releasing vancomycin and dexamethasone to achieve early postoperative infection prevention and inflammation regulation. Meanwhile, the growth factor microcapsules employ a non-responsive chitosan-polylactic acid wall material, which continuously releases fibroblast growth factors through slow polymer degradation in a neutral environment, ensuring a stable supply of tissue regeneration signals after inflammation subsides. This two-stage release mechanism of "anti-inflammatory first, then repair" avoids the problem of growth factors becoming ineffective due to the inflammatory environment in traditional simultaneous release modes, improving treatment efficiency and reducing side effects.

[0036] 3. This invention utilizes the covalent cross-linking reaction between the epoxy groups of 1,4-butanediol diglycidyl ether and the hyperbranched polyester hydroxyl groups to form a stable three-dimensional chemical network. This not only significantly improves the mechanical strength and swelling resistance of the material but also firmly anchors the microcapsules within the support layer. Compared to physical loading methods, chemical cross-linking greatly enhances the microcapsule retention rate, preventing drug loss due to fluid erosion or material degradation in the physiological environment. Simultaneously, the adjustable cross-linking density and degradation characteristics allow the material degradation cycle to match the tissue regeneration process. While providing continuous mechanical support, it gradually releases the porous structure to guide the ingrowth of new tissue, achieving a seamless transition between material degradation and functional replacement.

[0037] 4. This invention integrates three major functions—mechanical support, antibacterial and anti-inflammatory properties, and sustained release of growth factors—into a single material system: a hyperbranched polyester skeleton provides dynamic mechanical support, pH-responsive microcapsules precisely regulate the inflammation-repair sequence, and a chemical cross-linking network ensures structural stability. This multi-dimensional synergistic effect can significantly reduce postoperative infection rates and adhesion formation in thoracic and abdominal surgeries, and accelerate wound healing by promoting fibroblast proliferation and collagen deposition. It is particularly suitable for complex surgical scenarios such as digestive tract reconstruction and tumor resection, providing an integrated "support-anti-inflammatory-regeneration" solution for clinical practice, overcoming the limitations of traditional materials with single functions and disconnected treatment processes.

[0038] 5. The material system used in this invention has a clear degradable pathway and safe metabolites, ensuring no toxic residues during the gradual degradation process in vivo: the hyperbranched copolymer with glycerol, lactic acid, and glycolic acid as monomers is degraded through ester bond hydrolysis, with the main products being lactic acid, glycolic acid, and glycerol. Lactic acid is a natural intermediate in human carbohydrate metabolism and can be completely metabolized into CO2 and H2O through the tricarboxylic acid cycle. Glycolic acid can be excreted in urine or participate in gluconeogenesis. Glycerol, as an endogenous substance, directly participates in lipid metabolism. None of the three are biotoxic. Chitosan can be degraded into glucosamine and glucose, and is a component of the extracellular matrix, possessing natural... Biocompatibility: Polylactic acid segments break down into lactic acid via ester bond cleavage, following the body's inherent metabolic pathway; the acylhydrazone bonds in the antibacterial microcapsule wall material hydrolyze into oxaloacetate dihydrazide and glyceraldehyde in an acidic inflammatory environment. Oxaloacetate dihydrazide can be further metabolized into carbon dioxide and ammonia, which are excreted through the liver detoxification pathway. Glyceraldehyde, as an intermediate product of glycolysis, can be directly utilized by cells or converted into pyruvate to enter the metabolic cycle; soybean lecithin degrades into glycerol, fatty acids, and choline, all of which are components of cell membranes; genipin, as a natural cross-linking agent, forms stable covalent bonds after cross-linking with chitosan, and its degradation products are low-molecular-weight phenolic compounds, which are excreted after being metabolized by the liver; 1,4-butanediol diglycidyl ether cross-linking agent hydrolyzes into butanediol and glycerol via ether bond hydrolysis, both of which are non-toxic substances, and butanediol is a commonly used solvent in the cosmetics and pharmaceutical fields, and its safety has been widely verified. Attached Figure Description

[0039] Figure 1 The 1H NMR spectrum of the acylhydrazone compound prepared in Example 2 of this invention;

[0040] Figure 2 The 1H NMR spectrum of the carboxylated acylhydrazone compound prepared in Example 2 of this invention. Detailed Implementation

[0041] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments.

[0042] The reagent raw materials used in the embodiments of the present invention are sourced from the following sources:

[0043] Glycerin was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., purity: 99.7% (biotechnology grade); lactic acid was purchased from Jinan Yuno Chemical Co., Ltd., purity: food grade; glycolic acid was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., purity: 98%; p-toluenesulfonic acid was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., purity: 99%; oxaloacetic acid dihydrazide was purchased from Shanghai Bide Pharmaceutical Technology Co., Ltd., purity: 98%; glyceraldehyde was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., purity: 97%; sodium periodate was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., purity: 99.5%; chitosan-polylactic acid copolymer was purchased from Xi'an Qiyue Biotechnology Co., Ltd.; soybean lecithin was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., purity: biotechnology grade; genipin was purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Limited liability company, purity: 98%; phosphate buffer solution purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., pH=7.4; 1-ethyl-(3-dimethylaminopropyl)carbodiimide purchased from Shanghai Maclean Biochemical Technology Co., Ltd., purity: 98%; N-hydroxysuccinimide purchased from Shanghai Maclean Biochemical Technology Co., Ltd., biotechnology grade purity; 1,4-butanediol diglycidyl ether purchased from Tianjin Xiens Biochemical Technology Co., Ltd., purity: 98%; borax buffer purchased from Shanghai Enzyme-Linked Biotechnology Co., Ltd., pH=9.0; fibroblast growth factor purchased from Hunan Huibaishi Biotechnology Co., Ltd., purity: 95%; vancomycin purchased from Hunan Huibaishi Biotechnology Co., Ltd., purity: 98%; dexamethasone purchased from Hunan Huibaishi Biotechnology Co., Ltd., purity: 99%.

[0044] Example 1: A specific method for preparing a tissue reinforcement material for thoracic and abdominal surgery, comprising the following steps:

[0045] (1) Under nitrogen protection, 5g of glycerol, 100g of lactic acid, 100g of glycolic acid and 0.25g of p-toluenesulfonic acid were added to the reaction vessel, heated to 100℃ and stirred for 30min. Then the temperature was raised to 130℃ and the pressure was reduced to 5KPa. The reaction was carried out for 4h. After cooling to room temperature, the solid obtained was washed and dried and then added to 1000g of dichloromethane. The mixture was stirred for 20min and then poured onto a glass plate. After the solvent was evaporated by heating to 35℃, the film was peeled off. The film was then washed and dried to obtain the strength support layer material.

[0046] (2) Add 10g of oxalic acid dihydrazide and 80g of deionized water to the reaction vessel, stir, heat to 70℃, then add 10g of glyceraldehyde to 30g of ethanol to prepare glyceraldehyde ethanol solution, add glyceraldehyde ethanol solution to the reaction vessel, stir and react for 3h, cool to room temperature, filter, and the obtained white solid is washed with ethanol / water mixed solution (ethanol and water are mixed in a weight ratio of 3:7) and dried to obtain acylhydrazone compound;

[0047] (3) Add 8g of the acylhydrazone compound obtained in (2) to 64g of deionized water, adjust the pH to 9, add 8g of sodium periodate, stir the reaction at room temperature for 1h, filter to collect the solid, wash and dry to obtain the carboxylated acylhydrazone compound;

[0048] (4) Add 2g of chitosan-polylactic acid copolymer and 0.5g of soybean lecithin to 100g of dichloromethane and stir at room temperature for 20min to obtain an oil phase. Then add 0.01g of bFGF to 20g of deionized water to obtain an aqueous phase. Pour the aqueous phase into the oil phase and add 0.02g of genipin. Stir at 1000rpm for 1.5h. After drying and evaporating the solvent, collect the microcapsules by centrifugation, wash them, and freeze-dry them to obtain growth factor microcapsules.

[0049] (5) Add 5g of the carboxylated hydrazone compound obtained in (3) to 400g of phosphate buffer solution, add 0.25g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 0.25g of N-hydroxysuccinimide, stir for 30min, then add 25g of chitosan-polylactic acid copolymer, heat to 35℃, react for 3h, cool to room temperature, filter, wash and dry to obtain chitosan-polylactic acid-hydrazone copolymer;

[0050] (6) Add 5g of chitosan-polylactic acid-hydrazone copolymer obtained in (5) and 1.25g of soybean lecithin to 250g of dichloromethane, stir at room temperature for 20min to obtain an oil phase, then add 0.25g of antibacterial and anti-inflammatory agent (vancomycin and dexamethasone mixed in a weight ratio of 1:1) to 50g of deionized water, stir for 20min to obtain an aqueous phase, pour the aqueous phase into the oil phase, add 0.05g of genipin, stir at 1000rpm for 1.5h, dry the solvent after it evaporates, collect the microcapsules by centrifugation, wash them, and freeze-dry them to obtain anti-inflammatory and antibacterial microcapsules;

[0051] (7) Immerse 100g of the strength support layer material obtained in (1) in 1000g of borax buffer containing 80g of 1,4-butanediol diglycidyl ether, heat to 40°C, shake for 1h, then wash with deionized water, add to 1000g of borax buffer, add 1g of growth factor microcapsules obtained in (4) and 2g of anti-inflammatory and antibacterial microcapsules obtained in (6), heat to 35°C, shake for 1h, and the product is washed and dried to obtain tissue reinforcement material for thoracic and abdominal surgery.

[0052] Example 2: A specific method for preparing a tissue reinforcement material for thoracic and abdominal surgery, comprising the following steps:

[0053] (1) Under nitrogen protection, 5g glycerol, 83g lactic acid, 83g glycolic acid and 0.27g p-toluenesulfonic acid were added to the reaction vessel, heated to 105℃ and stirred for 45min, then heated to 135℃ and reduced to 7KPa, reacted for 5h, cooled to room temperature, and the resulting solid was washed and dried and then added to 833g dichloromethane and stirred for 25min. Then it was poured onto a glass plate, heated to 37℃ to evaporate the solvent, and peeled off to obtain a film. The film was then washed and dried to obtain a strength support layer material.

[0054] (2) Add 3g of oxalic acid dihydrazide and 30g of deionized water to the reaction vessel, stir, heat to 80℃, then add 3g of glyceraldehyde to 15g of ethanol to prepare glyceraldehyde ethanol solution, add glyceraldehyde ethanol solution to the reaction vessel, stir and react for 4h, cool to room temperature, filter, and wash the obtained white solid with ethanol / water mixed solution (ethanol and water are mixed in a weight ratio of 3:7) and dry to obtain acylhydrazone compound;

[0055] (3) Add 3g of the acylhydrazone compound obtained in (2) to 30g of deionized water, adjust the pH to 10, add 3g of sodium periodate, stir the reaction at room temperature for 2h, filter to collect the solid, wash and dry to obtain the carboxylated acylhydrazone compound;

[0056] (4) Add 5g of chitosan-polylactic acid copolymer and 1.9g of soybean lecithin to 125g of dichloromethane and stir at room temperature for 30min to obtain an oil phase. Then add 0.07g of bFGF to 37.5g of deionized water to obtain an aqueous phase. Pour the aqueous phase into the oil phase and add 0.015g of genipin. Stir at 1200rpm for 2h. After drying and evaporating the solvent, collect the microcapsules by centrifugation, wash them, and freeze-dry them to obtain growth factor microcapsules.

[0057] (5) Add 1.25g of the carboxylated hydrazone compound obtained in (3) to 125g of phosphate buffer solution, add 0.075g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 0.075g of N-hydroxysuccinimide, stir for 35min, then add 10g of chitosan-polylactic acid copolymer, heat to 40℃, react for 4h, cool to room temperature, filter, wash and dry to obtain chitosan-polylactic acid-hydrazone copolymer;

[0058] (6) Add 10g of the chitosan-polylactic acid-hydrazone copolymer obtained in (5) and 3.75g of soybean lecithin to 250g of dichloromethane, stir at room temperature for 30min to obtain an oil phase, then add 0.3g of antibacterial and anti-inflammatory agent (vancomycin and dexamethasone mixed in a weight ratio of 1:1) to 100g of deionized water, stir for 30min to obtain an aqueous phase, pour the aqueous phase into the oil phase, add 0.25g of genipin, stir at 1250rpm for 2h, dry the solvent after evaporation, centrifuge to collect the microcapsules, wash and freeze dry to obtain anti-inflammatory and antibacterial microcapsules;

[0059] (7) Immerse 100g of the strength support layer material obtained in (1) in 1500g of borax buffer containing 120g of 1,4-butanediol diglycidyl ether, heat to 43°C, shake for 1.5h, then wash with deionized water, add to 1500g of borax buffer, then add 2g of growth factor microcapsules obtained in (4) and 4g of anti-inflammatory and antibacterial microcapsules obtained in (6), heat to 40°C, shake for 1.5h, and the product is washed and dried to obtain tissue reinforcement material for thoracic and abdominal surgery.

[0060] Example 3: A specific method for preparing a tissue reinforcement material for thoracic and abdominal surgery, comprising the following steps:

[0061] (1) Under nitrogen protection, 5g glycerol, 75g lactic acid, 75g 0-hydroxyacetic acid and 0.25g p-toluenesulfonic acid were added to the reaction vessel, heated to 110℃ and stirred for 60min, then heated to 140℃ and reduced to 10KPa, reacted for 6h, cooled to room temperature, and the resulting solid was washed, dried and added to 750g dichloromethane, stirred for 30min, then poured onto a glass plate, heated to 40℃ to evaporate the solvent, peeled off to obtain a film, and the film was washed and dried to obtain a strength support layer material;

[0062] (2) Add 2g of oxalic acid dihydrazide and 24g of deionized water to the reaction vessel, stir, heat to 90℃, then add 2g of glyceraldehyde to 14g of ethanol to prepare glyceraldehyde ethanol solution, add glyceraldehyde ethanol solution to the reaction vessel, stir and react for 5h, cool to room temperature, filter, and the obtained white solid is washed with ethanol / water mixed solution (ethanol and water are mixed in a weight ratio of 3:7) and dried to obtain acylhydrazone compound;

[0063] (3) Add 2g of the acylhydrazone compound obtained in (2) to 24g of deionized water, adjust the pH to 11, add 2g of sodium periodate, stir the reaction at room temperature for 3h, filter to collect the solid, wash and dry to obtain the carboxylated acylhydrazone compound;

[0064] (4) Add 5g of chitosan-polylactic acid copolymer and 2g of soybean lecithin to 100g of dichloromethane and stir at room temperature for 40min to obtain an oil phase. Then add 0.1g of bFGF to 50g of deionized water to obtain an aqueous phase. Pour the aqueous phase into the oil phase and add 0.2g of genipin. Stir at 1500rpm for 2.5h. After drying and evaporating the solvent, collect the microcapsules by centrifugation, wash them, and freeze-dry them to obtain growth factor microcapsules.

[0065] (5) Add 1g of the carboxylated hydrazone compound obtained in (3) to 120g of phosphate buffer solution, add 0.07g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 0.07g of N-hydroxysuccinimide, stir for 40min, then add 10g of chitosan-polylactic acid copolymer, heat to 45℃, react for 5h, cool to room temperature, filter, wash and dry to obtain chitosan-polylactic acid-hydrazone copolymer;

[0066] (6) Add 10g of the chitosan-polylactic acid-hydrazone copolymer obtained in (5) and 4g of soybean lecithin to 200g of dichloromethane, stir at room temperature for 40min to obtain an oil phase, then add 0.3g of antibacterial and anti-inflammatory agent (vancomycin and dexamethasone mixed in a weight ratio of 1:1) to 100g of deionized water, stir for 40min to obtain an aqueous phase, pour the aqueous phase into the oil phase, add 0.4g of genipin, stir at 1500rpm for 2.5h, dry the solvent after evaporation, centrifuge to collect the microcapsules, wash and freeze dry to obtain anti-inflammatory and antibacterial microcapsules;

[0067] (7) Immerse 100g of the strength support layer material obtained in (1) in 2000g of borax buffer containing 300g of 1,4-butanediol diglycidyl ether, heat to 45°C, shake for 2h, then wash with deionized water, add to 2000g of borax buffer, then add 3g of growth factor microcapsules obtained in (4) and 5g of anti-inflammatory and antibacterial microcapsules obtained in (6), heat to 45°C, shake for 2h, and the product is washed and dried to obtain tissue reinforcement material for thoracic and abdominal surgery.

[0068] Comparative Example 1: The difference between Comparative Example 1 and Example 2 is that the wall material of the growth factor microcapsules is also made of chitosan-polylactic acid-hydrazone copolymer. The specific preparation method is as follows: A specific preparation method of a tissue reinforcement material for thoracic and abdominal surgery includes the following steps:

[0069] (1) Under nitrogen protection, 5g glycerol, 83g lactic acid, 83g glycolic acid and 0.27g p-toluenesulfonic acid were added to the reaction vessel, heated to 105℃ and stirred for 45min, then heated to 135℃ and reduced to 7KPa, reacted for 5h, cooled to room temperature, and the resulting solid was washed and dried and then added to 833g dichloromethane and stirred for 25min. Then it was poured onto a glass plate, heated to 37℃ to evaporate the solvent, and peeled off to obtain a film. The film was then washed and dried to obtain a strength support layer material.

[0070] (2) Add 3g of oxalic acid dihydrazide and 30g of deionized water to the reaction vessel, stir, heat to 80℃, then add 3g of glyceraldehyde to 15g of ethanol to prepare glyceraldehyde ethanol solution, add glyceraldehyde ethanol solution to the reaction vessel, stir and react for 4h, cool to room temperature, filter, and wash the obtained white solid with ethanol / water mixed solution (ethanol and water are mixed in a weight ratio of 3:7) and dry to obtain acylhydrazone compound;

[0071] (3) Add 3g of the acylhydrazone compound obtained in (2) to 30g of deionized water, adjust the pH to 10, add 3g of sodium periodate, stir the reaction at room temperature for 2h, filter to collect the solid, wash and dry to obtain the carboxylated acylhydrazone compound;

[0072] (4) Add 1.88g of the carboxylated hydrazone compound obtained in (3) to 187.5g of phosphate buffer solution, add 0.113g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 0.113g of N-hydroxysuccinimide, stir for 35min, then add 15g of chitosan-polylactic acid copolymer, heat to 40℃, react for 4h, cool to room temperature, filter, wash and dry to obtain chitosan-polylactic acid-hydrazone copolymer;

[0073] (5) Add 5g of chitosan-polylactic acid-hydrazone copolymer obtained in (4) and 1.9g of soybean lecithin to 125g of dichloromethane, stir at room temperature for 30min to obtain an oil phase, then add 0.07g of bFGF to 37.5g of deionized water to obtain an aqueous phase, pour the aqueous phase into the oil phase, add 0.015g of genipin, stir at 1200rpm for 2h, dry the solvent after evaporation, centrifuge to collect the microcapsules, wash and freeze dry to obtain growth factor microcapsules;

[0074] (6) Add 10g of the chitosan-polylactic acid-hydrazone copolymer obtained in (4) and 3.75g of soybean lecithin to 250g of dichloromethane, stir at room temperature for 30min to obtain an oil phase, then add 0.3g of antibacterial and anti-inflammatory agent (vancomycin and dexamethasone mixed in a weight ratio of 1:1) to 100g of deionized water, stir for 30min to obtain an aqueous phase, pour the aqueous phase into the oil phase, add 0.25g of genipin, stir at 1250rpm for 2h, dry the solvent after evaporation, centrifuge to collect the microcapsules, wash and freeze dry to obtain anti-inflammatory and antibacterial microcapsules;

[0075] (7) Immerse 100g of the strength support layer material obtained in (1) in 1500g of borax buffer containing 120g of 1,4-butanediol diglycidyl ether, heat to 43°C, shake for 1.5h, then wash with deionized water, add to 1500g of borax buffer, then add 2g of growth factor microcapsules obtained in (5) and 4g of anti-inflammatory and antibacterial microcapsules obtained in (6), heat to 40°C, shake for 1.5h, and the product is washed and dried to obtain tissue reinforcement material for thoracic and abdominal surgery.

[0076] Comparative Example 2: The difference between Comparative Example 2 and Example 2 is that the wall material of both the growth factor microcapsules and the anti-inflammatory and antibacterial microcapsules is made of chitosan-polylactic acid copolymer. The specific preparation method is as follows: A specific preparation method of a tissue reinforcement material for thoracic and abdominal surgery includes the following steps:

[0077] (1) Under nitrogen protection, 5g glycerol, 83g lactic acid, 83g glycolic acid and 0.27g p-toluenesulfonic acid were added to the reaction vessel, heated to 105℃ and stirred for 45min, then heated to 135℃ and reduced to 7KPa, reacted for 5h, cooled to room temperature, and the resulting solid was washed and dried and then added to 833g dichloromethane and stirred for 25min. Then it was poured onto a glass plate, heated to 37℃ to evaporate the solvent, and peeled off to obtain a film. The film was then washed and dried to obtain a strength support layer material.

[0078] (2) Add 5g of chitosan-polylactic acid copolymer and 1.9g of soybean lecithin to 125g of dichloromethane and stir at room temperature for 30min to obtain an oil phase. Then add 0.07g of bFGF to 37.5g of deionized water to obtain an aqueous phase. Pour the aqueous phase into the oil phase and add 0.015g of genipin. Stir at 1200rpm for 2h. After drying and evaporating the solvent, collect the microcapsules by centrifugation, wash them, and freeze-dry them to obtain growth factor microcapsules.

[0079] (3) Add 10g of chitosan-polylactic acid copolymer and 3.75g of soybean lecithin to 250g of dichloromethane and stir at room temperature for 30min to obtain an oil phase. Then add 0.3g of antibacterial and anti-inflammatory agent (vancomycin and dexamethasone mixed in a weight ratio of 1:1) to 100g of deionized water and stir for 30min to obtain an aqueous phase. Pour the aqueous phase into the oil phase and add 0.25g of genipin. Stir at 1250rpm for 2h. After drying and evaporating the solvent, collect the microcapsules by centrifugation, wash, and freeze-dry to obtain anti-inflammatory and antibacterial microcapsules.

[0080] (4) Immerse 100g of the strength support layer material obtained in (1) in 1500g of borax buffer containing 120g of 1,4-butanediol diglycidyl ether, heat to 43°C, shake for 1.5h, then wash with deionized water, add to 1500g of borax buffer, then add 2g of growth factor microcapsules obtained in (2) and 4g of anti-inflammatory and antibacterial microcapsules obtained in (3), heat to 40°C, shake for 1.5h, and the product is washed and dried to obtain tissue reinforcement material for thoracic and abdominal surgery.

[0081] Comparative Example 3: The difference between Comparative Example 3 and Example 2 is that the strength support layer material is made of a copolymer of lactic acid and glycolic acid, and the specific preparation method is as follows: A specific preparation method of a tissue reinforcement material for thoracic and abdominal surgery includes the following steps:

[0082] (1) Add 120g of polylactic acid-glycolic acid copolymer to 600g of dichloromethane, stir for 25min, then pour it onto a glass plate, heat to 37℃ to evaporate the solvent, peel off to obtain a film, and then wash and dry the film to obtain a strength support layer material.

[0083] (2) Add 3g of oxalic acid dihydrazide and 30g of deionized water to the reaction vessel, stir, heat to 80℃, then add 3g of glyceraldehyde to 15g of ethanol to prepare glyceraldehyde ethanol solution, add glyceraldehyde ethanol solution to the reaction vessel, stir and react for 4h, cool to room temperature, filter, and wash the obtained white solid with ethanol / water mixed solution (ethanol and water are mixed in a weight ratio of 3:7) and dry to obtain acylhydrazone compound;

[0084] (3) Add 3g of the acylhydrazone compound obtained in (2) to 30g of deionized water, adjust the pH to 10, add 3g of sodium periodate, stir the reaction at room temperature for 2h, filter to collect the solid, wash and dry to obtain the carboxylated acylhydrazone compound;

[0085] (4) Add 5g of chitosan-polylactic acid copolymer and 1.9g of soybean lecithin to 125g of dichloromethane and stir at room temperature for 30min to obtain an oil phase. Then add 0.07g of bFGF to 37.5g of deionized water to obtain an aqueous phase. Pour the aqueous phase into the oil phase and add 0.015g of genipin. Stir at 1200rpm for 2h. After drying and evaporating the solvent, collect the microcapsules by centrifugation, wash them, and freeze-dry them to obtain growth factor microcapsules.

[0086] (5) Add 1.25g of the carboxylated hydrazone compound obtained in (3) to 125g of phosphate buffer solution, add 0.075g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 0.075g of N-hydroxysuccinimide, stir for 35min, then add 10g of chitosan-polylactic acid copolymer, heat to 40℃, react for 4h, cool to room temperature, filter, wash and dry to obtain chitosan-polylactic acid-hydrazone copolymer;

[0087] (6) Add 10g of the chitosan-polylactic acid-hydrazone copolymer obtained in (5) and 3.75g of soybean lecithin to 250g of dichloromethane, stir at room temperature for 30min to obtain an oil phase, then add 0.3g of antibacterial and anti-inflammatory agent (vancomycin and dexamethasone mixed in a weight ratio of 1:1) to 100g of deionized water, stir for 30min to obtain an aqueous phase, pour the aqueous phase into the oil phase, add 0.25g of genipin, stir at 1250rpm for 2h, dry the solvent after evaporation, centrifuge to collect the microcapsules, wash and freeze dry to obtain anti-inflammatory and antibacterial microcapsules;

[0088] (7) Immerse 100g of the strength support layer material obtained in (1) in 1500g of borax buffer containing 120g of 1,4-butanediol diglycidyl ether, heat to 43°C, shake for 1.5h, then wash with deionized water, add to 1500g of borax buffer, then add 2g of growth factor microcapsules obtained in (4) and 4g of anti-inflammatory and antibacterial microcapsules obtained in (6), heat to 40°C, shake for 1.5h, and the product is washed and dried to obtain tissue reinforcement material for thoracic and abdominal surgery.

[0089] Comparative Example 4: The difference between Comparative Example 4 and Example 2 is that 1,4-butanediol diglycidyl ether is not added. The microcapsules are physically loaded onto the strength support layer material. The specific preparation process is as follows: A specific preparation method of a tissue reinforcement material for thoracic and abdominal surgery includes the following steps:

[0090] (1) Under nitrogen protection, 5g glycerol, 83g lactic acid, 83g glycolic acid and 0.27g p-toluenesulfonic acid were added to the reaction vessel, heated to 105℃ and stirred for 45min, then heated to 135℃ and reduced to 7KPa, reacted for 5h, cooled to room temperature, and the resulting solid was washed and dried and then added to 833g dichloromethane and stirred for 25min. Then it was poured onto a glass plate, heated to 37℃ to evaporate the solvent, and peeled off to obtain a film. The film was then washed and dried to obtain a strength support layer material.

[0091] (2) Add 3g of oxalic acid dihydrazide and 30g of deionized water to the reaction vessel, stir, heat to 80℃, then add 3g of glyceraldehyde to 15g of ethanol to prepare glyceraldehyde ethanol solution, add glyceraldehyde ethanol solution to the reaction vessel, stir and react for 4h, cool to room temperature, filter, and wash the obtained white solid with ethanol / water mixed solution (ethanol and water are mixed in a weight ratio of 3:7) and dry to obtain acylhydrazone compound;

[0092] (3) Add 3g of the acylhydrazone compound obtained in (2) to 30g of deionized water, adjust the pH to 10, add 3g of sodium periodate, stir the reaction at room temperature for 2h, filter to collect the solid, wash and dry to obtain the carboxylated acylhydrazone compound;

[0093] (4) Add 5g of chitosan-polylactic acid copolymer and 1.9g of soybean lecithin to 125g of dichloromethane and stir at room temperature for 30min to obtain an oil phase. Then add 0.07g of bFGF to 37.5g of deionized water to obtain an aqueous phase. Pour the aqueous phase into the oil phase and add 0.015g of genipin. Stir at 1200rpm for 2h. After drying and evaporating the solvent, collect the microcapsules by centrifugation, wash them, and freeze-dry them to obtain growth factor microcapsules.

[0094] (5) Add 1.25g of the carboxylated hydrazone compound obtained in (3) to 125g of phosphate buffer solution, add 0.075g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 0.075g of N-hydroxysuccinimide, stir for 35min, then add 10g of chitosan-polylactic acid copolymer, heat to 40℃, react for 4h, cool to room temperature, filter, wash and dry to obtain chitosan-polylactic acid-hydrazone copolymer;

[0095] (6) Add 10g of the chitosan-polylactic acid-hydrazone copolymer obtained in (5) and 3.75g of soybean lecithin to 250g of dichloromethane, stir at room temperature for 30min to obtain an oil phase, then add 0.3g of antibacterial and anti-inflammatory agent (vancomycin and dexamethasone mixed in a weight ratio of 1:1) to 100g of deionized water, stir for 30min to obtain an aqueous phase, pour the aqueous phase into the oil phase, add 0.25g of genipin, stir at 1250rpm for 2h, dry the solvent after evaporation, centrifuge to collect the microcapsules, wash and freeze dry to obtain anti-inflammatory and antibacterial microcapsules;

[0096] (7) Spread 100g of the strength support layer material obtained in (1) on a glass plate, then add 2g of growth factor microcapsules obtained in (4) and 4g of anti-inflammatory and antibacterial microcapsules obtained in (6) to 100g of deionized water, spray them evenly on the strength support layer material, and obtain tissue reinforcement material for thoracic and abdominal surgery after drying.

[0097] Performance testing:

[0098] 1. Mechanical property testing: The tissue-reinforcing materials prepared in Examples 1-3 and Comparative Examples 3-4 were cut into strips of 50mm × 10mm. Using a universal testing machine, at room temperature, the tensile strength and elongation at break of the materials were tested at a tensile speed of 5mm / min. The experimental results are shown in Table 2.

[0099] 2. Cell adhesion rate test: The tissue reinforcement materials prepared in Examples 1-3 and Comparative Examples 3-4 were cut to a size suitable for 12-well plates, placed in 12-well plates, and seeded with fibroblast suspension at a density of 1×10⁻⁶. 5 Cells / ml, 1ml per well, incubated at 37℃ for 24h, after which the tissue reinforcement materials were taken out, washed with phosphate buffered saline solution, stained with crystal violet for 15min, dissolved in anhydrous ethanol, and the absorbance value at 595nm was read using an ELISA reader. The absorbance value of Comparative Example 3 was set as 1. The cell adhesion rate of Examples 1-3 was calculated. The experimental results are shown in Table 2.

[0100] 3. Degradation time test: The tissue-reinforcing materials prepared in Examples 1-3 and Comparative Examples 3-4 were cut into strips of 50mm × 10mm and placed in a phosphate buffer solution at 37℃, 10ml, pH=7.2. The phosphate buffer solution was replaced every 5 days, and samples were taken every 7 days. The materials were lyophilized and weighed to calculate the weight loss rate. The weight loss rate of each sample was recorded, and the experimental results are shown in Table 3.

[0101] 4. pH response test: The tissue-strengthening materials prepared in Examples 1-3 and Comparative Examples 1-2 were cut into strips of 50mm × 10mm and immersed in 5ml of buffer solutions preheated to 37℃ with pH=6 and pH=7.2, respectively. The release start time T1 and the time to reach peak concentration T2 of growth factors and antibacterial and anti-inflammatory components in the buffer solutions were detected by HPLC. The experimental results are shown in Table 4.

[0102] 5. In vivo model experiment: The tissue reinforcement materials prepared in Examples 1-3 and Comparative Examples 1-4 were divided into 5 groups, and a blank control group was added. The blank control group was a tissue reinforcement material made of commercially available polylactic acid-glycolic acid copolymer, for a total of 6 groups. Each group used 8 SPF-grade male mice. 24 hours before the operation, LPS was injected locally into the wound to induce acute inflammation. After anesthesia, the mice were shaved and disinfected, and a 1.5cm longitudinal incision was made. The subcutaneous tissue was bluntly dissected to form a 2cm×2cm cavity. The appropriately sized tissue reinforcement material was implanted and sutured to fully adhere to the wound. The degree of wound inflammation was scored 3 days after the operation, and the criteria are shown in Table 1.

[0103] Table 1 Scoring Criteria

[0104]

[0105] The inflammation severity score for each group was the average of the sum of the redness and swelling score and the exudate / suppuration score for each mouse in each group; the infection rate for each group was calculated 7 days post-surgery. If the wound has pus, an odor, or the animal is lethargic and refuses to eat, it is considered an infection. Finally, the average wound healing time for each group of experiments was recorded, and the experimental results are shown in Table 5.

[0106] Table 2 Mechanical properties and cell adhesion rate tests

[0107] Table 3 Degradation Time Test

[0108]

[0109] Table 4 pH Response Test

[0110]

[0111] Table 5 In vivo model experiments

[0112]

[0113] Performance Analysis:

[0114] As can be seen from the experimental data in Tables 2-5, the tissue reinforcement material prepared by this invention has good mechanical properties. The high tensile strength meets the support requirements of the reinforcement material, and the improved elongation at break adapts to the bonding requirements under complex veneer conditions. At the same time, the hyperbranched structure brings more surface hydroxyl groups, which enhances hydrophilicity and increases cell adhesion rate, enabling tissue cells to grow along the material skeleton and providing a mechanical framework for tissue repair. Compared with traditional polylactic acid-glycolic acid copolymers, the hyperbranched cross-linked material improves the degradation time, meets the mechanical support required during the tissue growth stage, and avoids the problem of strength support failure caused by excessively rapid degradation. With the addition of microcapsules with different release rates, inflammation is regulated first and then growth is promoted, avoiding the loss of growth-promoting function of growth factors due to the presence of inflammation. Finally, in the in vivo model experiment, the results showed "low inflammation - no infection - rapid healing". Among them, Example 2 has the best overall performance.

[0115] As can be seen from the data in Table 2, the tissue-strengthening material prepared in Example 2 exhibits good mechanical properties and cell adhesion rate. This may be because: during the preparation process of Example 2, glycerol served as the branching core to construct a three-dimensional hyperbranched network. The hyperbranched structure forms a "rigid-flexible" structure through the entanglement between molecular chains and the hydrogen bonding of hydroxyl groups. Compared with the linear polymer used in Comparative Example 3, the hyperbranched structure can more uniformly disperse stress, improving toughness while maintaining strength. In Comparative Example 4, the lack of 1,4-butanediol diglycidyl ether led to a decrease in tensile strength, confirming that 1,4-butanediol diglycidyl ether can act as a crosslinking agent to strengthen the material. Structural role; meanwhile, the cell adhesion rate of Example 2 was significantly higher than that of the conventional material used in Comparative Example 3. This may be because the hyperbranched polymer prepared in Example 2 has abundant hydroxyl groups on its surface. The hydroxyl groups adsorb serum proteins through hydrogen bonding, forming a biomimetic interface that facilitates cell adhesion. The hydroxyl groups can also enhance the hydrophilicity of the material, thereby promoting cell spread. In Comparative Example 4, due to the physical loading of the microcapsules, the uneven loading process caused the hydroxyl sites to be covered by the microcapsules. Although there was no cross-linking and the number of surface hydroxyl groups was greater than that in Example 2, the uneven loading shielded more hydroxyl sites, resulting in a decrease in the cell adhesion rate of Comparative Example 4.

[0116] As can be seen from the experimental data in Table 3, the degradation cycle of the reinforcing material prepared in Example 2 is more compatible with the tissue regeneration process, and can sustainably provide mechanical support for tissue regeneration. This may be because: the compatibility between the degradation cycle and the tissue regeneration process in Example 2 stems from the synergistic regulation mechanism of its multi-level molecular structure. The hyperbranched polymer skeleton in the material system generates molecular chain entanglement effect through a three-dimensional network, combined with a stable covalent network constructed by a crosslinking agent, forming a gradient degradation characteristic: in the initial stage, the tight intermolecular forces maintain the integrity of the material, providing a rigid support framework for cell migration and tissue remodeling; as time goes on, the directional hydrolysis of the main chain ester bonds in a neutral environment and the gradual dissociation of the branched nodes form a dynamic equilibrium, gradually releasing appropriate pores. The gap structure guides the orderly growth of new tissue and establishes mechanical transmission channels. This controllable degradation mode, from the surface to the inside and from the local to the whole, avoids the early support failure caused by the rapid disintegration of traditional materials and prevents the long-term foreign matter retention caused by excessive cross-linking, achieving a precise match between the degradation cycle and the repair process. In contrast, Comparative Example 3 uses a traditional linear polylactic acid-glycolic acid copolymer, whose regular molecular chain arrangement forms a highly crystalline region. Water molecules preferentially penetrate along the grain boundaries to induce rapid bulk degradation. Although Comparative Example 4 retains the hyperbranched framework, it lacks a cross-linking network. After the material swells, it forms a loose porous structure, and the specific surface area increases sharply, accelerating the hydrolysis of ester bonds. Moreover, the physically adsorbed microcapsules form stress concentration points on the material surface, inducing crack propagation and leading to non-uniform degradation.

[0117] As can be seen from the data in Table 4, the tissue-strengthening material prepared in Example 2 can first regulate inflammation and then promote growth. This may be because: the wall material of the antibacterial microcapsules in Example 2 constructs a pH-responsive unit by introducing acylhydrazone bonds: under the weakly acidic conditions of the inflammatory microenvironment, the imine nitrogen atom of the acylhydrazone bond is preferentially protonated, triggering the reconstruction of the intramolecular charge distribution, causing the π electron cloud of the C=N double bond to shift towards the nitrogen end, weakening the binding energy with the neighboring carbon atom, and thus triggering the rapid breakage of the molecular chain, achieving the rapid release of antibacterial and anti-inflammatory components. On the other hand, the wall material of the growth factor microcapsules is based on the ester bond design, and its degradation depends on the nucleophilic attack of water molecules in a neutral environment: the carbonyl oxygen of the ester bond combines with H2O through hydrogen bonds. A tetrahedral transition state is formed, followed by slow, stepwise hydrolysis, with the release rate controlled by the kinetics of the material's bulk degradation. In contrast, the failure of Comparative Example 1 stemmed from confusion of chemical bond functions. After the growth factor microcapsules mistakenly introduced acylhydrazone bonds, the rapid dissociation of their wall material under acidic conditions led to premature exposure of the growth factors to a protease-rich inflammatory environment, resulting in the enzymatic deactivation of the active ingredients. Comparative Example 2, due to its simplistic chemical bond design, lacked selective environmental response and could not distinguish the differences in the microenvironment between the inflammatory and repair phases, leading to delayed antibacterial agent release and disordered growth factor release. This hierarchical response system, constructed through the intrinsic reactivity of chemical bonds, achieves a precise correspondence between drug release behavior and the biological needs of the tissue repair stage.

[0118] As can be seen from the data in Table 5, mice using the reinforcing material prepared in Example 2 exhibited postoperative conditions of "low inflammation, no infection, and rapid healing." This may be due to the synergistic effect of its multi-level responsive material system: the gradient degradation network constructed through a hyperbranched polymer skeleton provides continuous mechanical support, while the dual-pathway microcapsule system achieves precise timing release based on the intrinsic properties of chemical bonds. The acylhydrazone bonds of the antibacterial microcapsules trigger rapid hydrolysis in the inflammatory microenvironment, releasing the drug first to inhibit infection, while the ester bonds of the growth factor microcapsules rely on a neutral environment to slowly release the active ingredient, avoiding premature inactivation. In contrast, Comparative Example 1 suffered from simultaneous release of both components due to functional mismatch of chemical bonds, with anti-inflammatory and regenerative effects interfering with each other; Comparative Example 2 lost its environmental responsiveness due to the simplification of chemical bonds, resulting in disordered release timing; the linear polymer structure of Comparative Example 3 caused an imbalance in degradation rates, leading to premature failure of mechanical support; and Comparative Example 4 suffered from microcapsule detachment and material structure collapse due to the lack of cross-linking. The blank control completely lacked anti-inflammatory, antibacterial, and growth factor components, failing to meet the repair needs. This hierarchical regulation of chemical bond reactivity and multi-dimensional synergistic design of material structure is the fundamental reason why Example 2 achieves precise regulation of the entire process of "infection control-inflammation resolution-tissue regeneration".

[0119] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing a tissue reinforcement material for use in thoracoabdominal surgery, characterized by, Comprising the following steps: S1. Glycerol, lactic acid, glycolic acid and p-toluene sulfonic acid were added into a reaction kettle under nitrogen protection, and stirred for 30-60 min after warming to 100-110℃, then warmed to 130-140℃ and reduced to 5-10 KPa, reacted for 4-6 h, and cooled to room temperature, the obtained solid was washed and dried, then added into dichloromethane, stirred for 20-30 min, then poured on a glass plate, warmed to 35-40℃ to volatilize the solvent, and the film was peeled off, washed and dried to obtain the strength support layer material; S2. Oxalyl dihydrazide and deionized water were added into a reaction vessel, stirred and warmed to 70-90℃, then glycolaldehyde was added into ethanol to prepare a glycolaldehyde ethanol solution, the glycolaldehyde ethanol solution was added into the reaction vessel, and stirred and reacted for 3-5 h, then cooled to room temperature, filtered, and the obtained white solid was washed and dried with ethanol / water mixed solution to obtain the acylhydrazone compound; S3. The acylhydrazone compound obtained in S2 was added into deionized water, the pH was adjusted to 9-11, and sodium periodate was added, stirred and reacted at room temperature for 1-3 h, the solid was collected by filtration, washed and dried to obtain the carboxylated acylhydrazone compound; S4. Chitosan-polylactic acid copolymer and soybean lecithin were added into dichloromethane, stirred at room temperature for 20-40 min to obtain an oil phase, then the growth factor was added into deionized water to obtain an aqueous phase, the aqueous phase was poured into the oil phase, and genipin was added, stirred at 1000-1500 rpm for 1.5-2.5 h, the microcapsules were collected by centrifugation after drying to volatilize the solvent, washed, and freeze-dried to obtain the growth factor microcapsules; S5. The carboxylated acylhydrazone compound obtained in S3 was added into a phosphate buffered saline solution, 1-ethyl-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide were added, stirred for 30-40 min, then chitosan-polylactic acid copolymer was added, warmed to 35-45℃, reacted for 3-5 h, cooled to room temperature, filtered, washed, and dried to obtain the chitosan-polylactic acid-acylhydrazone copolymer; S6. The chitosan-polylactic acid-acylhydrazone copolymer obtained in S5 and soybean lecithin were added into dichloromethane, stirred at room temperature for 20-40 min to obtain an oil phase, then the antibacterial and anti-inflammatory agent was added into deionized water, stirred for 20-40 min to obtain an aqueous phase, the aqueous phase was poured into the oil phase, and genipin was added, stirred at 1000-1500 rpm for 1.5-2.5 h, the microcapsules were collected by centrifugation after drying to volatilize the solvent, washed, and freeze-dried to obtain the anti-inflammatory and antibacterial microcapsules; S7. The strength support layer material obtained in S1 was immersed into a borax buffer solution containing 1,4-butanediol diglycidyl ether, warmed to 40-45℃, and oscillated for 1-2 h, then washed with deionized water, added into the borax buffer solution, and then added into the growth factor microcapsules obtained in S4 and the anti-inflammatory and antibacterial microcapsules obtained in S6, warmed to 35-45℃, oscillated for 1-2 h, and the product was washed and dried to obtain the tissue strengthening material for thoracic and abdominal surgery.

2. The method for preparing the tissue reinforcement material for thoracic and abdominal surgery according to claim 1, characterized in that, The glycerol, lactic acid, hydroxyacetic acid, p-toluenesulfonic acid and dichloromethane in S1 are in a weight ratio of 0.1-0.2:2-3:2-3:0.005-0.01:20-30.

3. The method for preparing the tissue reinforcement material for thoracic and abdominal surgery according to claim 1, characterized in that, The adipic acid dihydrazide, glycerol, deionized water and ethanol in S2 are in a weight ratio of 1:1:8-12:3-7, and the ethanol / water mixed solution refers to a mixture of ethanol and water in a weight ratio of 3:

7.

4. The method for preparing the tissue reinforcement material for thoracic and abdominal surgery according to claim 1, characterized in that, The acylhydrazone compound, sodium periodate and deionized water in S3 are in a weight ratio of 1:1:8-12.

5. The method for preparing the tissue reinforcement material for thoracic and abdominal surgery according to claim 1, characterized in that, The chitosan-polylactic acid copolymer, soybean lecithin, growth factor, genipin, dichloromethane and deionized water in S4 are in a weight ratio of 2-5:0.5-2:0.01-0.1:0.02-0.2:100:20-50, and the growth factor is fibroblast growth factor.

6. The method for preparing the tissue reinforcement material for thoracic and abdominal surgery according to claim 1, characterized in that, The carboxylated acylhydrazone compound, chitosan-polylactic acid copolymer, 1-ethyl-(3-dimethylaminopropyl) carbodiimide, N-hydroxysuccinimide and phosphate buffered saline solution in S5 are in a weight ratio of 1:5-10:0.05-0.07:0.05-0.07:80-120, and the phosphate buffered saline solution has a pH of 7.

4.

7. The method for preparing the tissue reinforcement material for thoracic and abdominal surgery according to claim 1, characterized in that, The chitosan-polylactic acid-acylhydrazone copolymer, soybean lecithin, antibacterial and anti-inflammatory agent, genipin, dichloromethane and deionized water in S6 are in a weight ratio of 2-5:0.5-2:0.1-0.15:0.02-0.2:100:20-50, and the antibacterial and anti-inflammatory agent refers to a mixture of vancomycin and dexamethasone in a weight ratio of 1:

1.

8. The method for preparing the tissue reinforcement material for thoracic and abdominal surgery according to claim 1, characterized in that, The strength support layer material, borax buffer solution containing 1,4-butanediol diglycidyl ether, borax buffer solution, growth factor microcapsule and anti-inflammatory and antibacterial microcapsule in S7 are in a weight ratio of 1:10-20:10-20:0.01-0.03:0.02-0.

05.

9. The method for preparing the tissue reinforcement material for thoracic and abdominal surgery according to claim 1, characterized in that, The content of 1,4-butanediol diglycidyl ether in the borax buffer solution containing 1,4-butanediol diglycidyl ether in S7 is 8-15 wt%, and the pH of the borax buffer solution is 9.

0.

10. A tissue reinforcement material for use in thoraco-abdominal surgery, characterized in that, The tissue strengthening material is prepared by the preparation method of any one of claims 1-9, the pH-responsive anti-inflammatory and antibacterial microcapsule containing an acylhydrazone bond and the growth factor microcapsule embedded in chitosan-polylactic acid are chemically grafted on the surface of the strength support layer material to form, is used for postoperative tissue repair and strengthening of thoracic and abdominal cavity, mechanical support is provided by the strength support layer material, the release of the growth factor microcapsule and the anti-inflammatory and antibacterial microcapsule is realized in sequence, the integration treatment of postoperative infection prevention, inflammation control and tissue regeneration is realized, and the tissue strengthening material is suitable for wound repair and adhesion prevention after digestive tract reconstruction and tumor resection.

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