Preparation method and application of PLGA / bioactive glass shape memory composite material

Abstract

The invention relates to the technical field of biomedical materials, and discloses a preparation method and application of a PLGA / bioactive glass shape memory composite.The preparation method comprises the following steps that 1, bioactive glass is modified with an amino silane coupling agent, and after the modified bioactive glass and PLGA are mixed and subjected to ball milling, a PLGA / BG mixture is obtained; (2) mixing the PLGA / BG mixture, an NH2-PEG-PCL copolymer and a pore-forming agent, adding the PCL / TPU shape memory material, mixing, putting into a closed container, and introducing supercritical CO2 for foaming; and (3) cooling to normal temperature, soaking in hot water to remove the pore-forming agent, and freeze-drying. The shape memory material is introduced into a supercritical CO2 foaming PLGA / bioactive glass composite system, so that the system has the body temperature responsive deformation capacity and is adaptive to the bone defect form, and the problem of shaping in an operation is solved.

Description

Technical Field

[0001] This invention relates to the technical field of biomedical materials, and in particular to a method for preparing and applying a PLGA / bioactive glass shape memory composite material. Background Technology

[0002] In the clinical application of bioactive glass as a bone repair material, directly using powdered bioactive glass poses risks such as poor shapeability, easy migration during surgery, and inducing local tissue inflammation due to the lack of physical support structure and manipulability. Patent CN114984307B discloses a shapeable bone repair material and its preparation method, which uses natural polymeric excipients such as glycerol or gelatin and bioactive glass to construct a composite system to improve material manipulability. However, its degradation kinetics are mismatched with the bone regeneration cycle; rapid hydrolysis of the excipients leads to premature loss of material support properties in the composite material, while bone tissue regeneration takes several months. This uncontrollable degradation rate easily causes secondary collapse of the repair area and limits the sustained osteoinductive effect of the bioactive glass.

[0003] Composites of PLGA and bioactive glass can address the aforementioned issues, but existing organic solvent methods and screw blending methods produce composites with inherent drawbacks. Organic solvents (such as chloroform and dichloromethane) are difficult to completely remove, and residual solvents may trigger local inflammation or cytotoxicity, affecting biocompatibility. The high temperature and shear force of the screw can cause PLGA molecular chains to break, reducing molecular weight, accelerating material hydrolysis, and resulting in uncontrollable degradation rates. Good bone implant materials require porous structures; relying on solvent evaporation to form pores is prone to pore wall collapse due to surface tension, leading to uneven pore sizes, closed pores, or non-connected pores, hindering cell migration and vascularization. In contrast, composites prepared by screw blending under conventional conditions are generally dense with fewer pores. Furthermore, achieving proper shaping during surgery for bone defect filling is a challenge. Powdered fillers are prone to disintegration and leakage, making fixation difficult, while blocky fillers are difficult to conform to irregularly shaped bone defects, affecting bone regeneration. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a method for preparing and applying a PLGA / bioactive glass shape memory composite material, which combines a stable three-dimensional structure, porosity, controllable degradation characteristics, and long-term bioactivity maintenance capability. It also contains a shape memory polymer, enabling precise fitting and long-term repair of bone defect morphology, adaptively fitting bone defect morphology, and reducing surgical trauma.

[0005] The objective of this invention is achieved through the following technical solution: In a first aspect, the present invention provides a method for preparing a PLGA / bioactive glass shape memory composite material, comprising the following steps: (1) Bioactive glass was modified with aminosilane coupling agent. The modified bioactive glass was mixed with PLGA and ball-milled to obtain a PLGA / BG mixture. (2) Mix PLGA / BG mixture, NH2-PEG-PCL copolymer and pore-forming agent, then add PCL / TPU shape memory material and mix. Place it in a sealed container, introduce supercritical CO2, the initial temperature is 35-40℃, the pressure is controlled at 20-25MPa, and the pressure is maintained for 120-180min. Then maintain the pressure and raise the temperature to 45-55℃, and maintain the pressure for 5-10min. After that, first quickly depressurize to 10-15MPa, the depressurization time is less than 2s, maintain for 5-10min, and then slowly depressurize to normal pressure, the depressurization time is 5-30s. (3) After cooling to room temperature, soak in hot water to remove pore-forming agent and freeze dry.

[0006] This invention introduces PCL / TPU shape memory material into PLGA / bioactive glass composite material. PCL / TPU shape memory material has the ability to recover its shape at near body temperature. After implantation, it can automatically trigger shape recovery under physiological conditions, achieving precise fit and long-term repair of bone defect morphology, adaptively fitting the bone defect morphology, and solving the problem of intraoperative shaping.

[0007] However, there are compatibility and hydrophilicity / hydrophobicity issues between PCL / TPU shape memory materials and PLGA / BG mixtures, which affect interfacial bonding. This is especially true in this invention, which uses supercritical CO2 to directly foam the powder / particles; the interfacial bonding directly impacts the structural stability and mechanical properties of the final material. Therefore, modifying the bioactive glass with an aminosilane coupling agent and introducing an NH2-PEG-PCL copolymer can improve interfacial bonding, thereby enhancing the overall material performance.

[0008] Furthermore, the mixing of multiphase materials leads to uneven foaming rates, and the formation of excessive interconnected pore structures in PCL / TPU shape memory materials hinders shape recovery due to the difficulty in storing elastic potential energy. Therefore, staged heating foaming achieves segmented saturation. Based on the chain segment movement characteristics of the material at different temperatures, CO2 initially easily escapes to the PLGA / BG phase, becoming enriched there. The PCL / TPU phase contains low-saturation CO2, and then heating triggers foaming. Simultaneously, the depressurization process is controlled with staged depressurization. Rapid depressurization first forms closed-cell structures, preserving shape memory capability. Holding pressure at 15 MPa for a period allows for uniform initial bubble growth, followed by slow depressurization to achieve moderate bubble connectivity. Due to the selective enrichment of CO2 controlled in the early stages, interconnected porous networks are formed primarily in the PLGA / BG phase. In addition, the addition of a pore-forming agent helps form interconnected channels without affecting the shape memory function of PCL / TPU. On the contrary, the increased pore structure reduces resistance to shape recovery, making it more conducive to expansion and adhesion to bone tissue. Therefore, the composite material in this invention can ensure good shape memory function while maintaining high porosity and pore connectivity.

[0009] Preferably, in step (1), the mass ratio of the modified bioactive glass to PLGA is 3:5-7; and the modification ratio of the aminosilane coupling agent in the modified bioactive glass is 5-10% of the mass of the bioactive glass.

[0010] Preferably, in step (1), the particle size of the bioactive glass is 10-100 μm; the particle size of the PLGA is 50-200 μm; the ball milling speed is 200-300 rpm and the time is 10-30 min.

[0011] Preferably, in step (1), an aminosilane coupling agent is used to modify the bioactive glass. The specific modification steps are as follows: immerse the bioactive glass powder in an ethanol solution containing an aminosilane coupling agent, heat it to 50-60℃ and react for 10-15 hours, then wash and dry it.

[0012] Preferably, in step (1), the aminosilane coupling agent includes one or more of γ-aminopropyltriethoxysilane, γ-aminopropyltrimethoxysilane, phenylaminomethyltriethoxysilane, and N-β(aminoethyl)-γ-aminopropylmethyldiethoxysilane.

[0013] Preferably, in step (2), the ratio of the PLGA / BG mixture to the PCL / TPU shape memory material is 70-80% : 20-30% by mass percentage.

[0014] The ratio of PLGA / BG mixture to PCL / TPU shape memory material affects the overall structural stability of the material. Simultaneously, shape recovery force must overcome tissue resistance, and the raw material ratio and pore structure both influence the magnitude of tissue resistance. Excessive tissue resistance results in a low shape recovery rate, making it difficult to conform to irregularly shaped bone defects, while insufficient tissue resistance leads to excessive expansion, potentially damaging newly formed bone. Furthermore, the different degradation rates of biodegradable materials can also reduce shape memory performance due to premature loss of mechanical support. Therefore, the raw material ratios used in this invention ensure that the composite material exhibits excellent shape recovery performance.

[0015] Preferably, in step (2), the amount of NH2-PEG-PCL copolymer added is 5-10% of the total mass of the PLGA / BG mixture and the PCL / TPU shape memory material; the average molecular weight of the NH2-PEG-PCL copolymer is 1000-2000 Da.

[0016] Preferably, in step (2), the amount of pore-forming agent added is 12-18% of the total mass of the PLGA / BG mixture and the PCL / TPU shape memory material; the pore-forming agent is PEG with an average molecular weight of 4000-6000.

[0017] Preferably, in step (2), the shape recovery temperature of the PCL / TPU shape memory material is 35-40℃. It is made of poly(ε-caprolactone diol) with an average molecular weight of 2000-3500 as soft segments and the reaction products of hexamethylene diisocyanate, 2,4-toluene diisocyanate and 1,4-butanediol as hard segments. The hard segments account for 20-27% of the mass of the PCL / TPU shape memory material. After curing and pulverizing, the material is obtained with a particle size of 50-200μm.

[0018] Preferably, in step (2), the preparation of the PCL / TPU shape memory material specifically includes the following steps: after melting poly(ε-caprolactone diol), cooling it to room temperature, adding hexamethylene diisocyanate and 2,4-toluene diisocyanate, heating it to 60-65℃ and stirring for 30-50 min; adding dimethyl carbonate, dibutyltin dilaurate and 1,4-butanediol in sequence, reacting at this temperature for 3-5 h, vacuum curing at 90-100℃, then taking it out, cooling it, and pulverizing it to obtain the PCL / TPU shape memory material with a particle size of 50-200 μm.

[0019] Preferably, the molar ratio of poly(ε-caprolactone diol), hexamethylene diisocyanate, 2,4-toluene diisocyanate, and 1,4-butanediol is 1:1:5:5; the amount of dimethyl carbonate added is 90-110% of the total mass of poly(ε-caprolactone diol), hexamethylene diisocyanate, 2,4-toluene diisocyanate, and 1,4-butanediol, and the amount of dibutyltin dilaurate added is 0.05-0.15% of the total mass.

[0020] Preferably, in step (3), the temperature of the hot water is 60-70℃ and the soaking time is 12-24h.

[0021] Preferably, in step (3), the freeze-drying temperature is -30°C to -20°C.

[0022] Secondly, the present invention also provides an application of PLGA / bioactive glass shape memory composite material in the field of bone repair.

[0023] The composite material prepared by this invention can be applied in the field of bone repair, and can be used as a bone repair material, bone implant material or bone filling material.

[0024] Compared with the prior art, the present invention has the following beneficial effects: (1) The preparation of the composite material does not use traditional organic solvents at all. Supercritical CO2 is used to directly permeate the premixed powder to achieve bubble foaming. This not only eliminates the risk of solvent residue, but also greatly improves biosafety and environmental protection. (2) The composite material has a porous structure that promotes cell attachment, proliferation and bone regeneration. Such a porous structure also helps to expose more bioactive glass to the physiological environment. Compared with dense PLGA / bioactive glass composite material, it can release the active ionic components of bioactive glass faster and enhance the osteogenic induction effect of bioactive glass, thus providing a material platform with great application prospects for tissue engineering and bone regeneration. (3) By precisely controlling the heating temperature, holding time and depressurization rate of supercritical CO2, and setting a stabilization period at a specific pressure point, the bubble size and distribution can be precisely controlled, and the pore size (50-300μm), porosity (>70%) and pore connectivity (>60%) can be controlled. This helps to enhance the osteogenic and vascular properties of the composite material as a bone filler, while ensuring good shape memory function (shape recovery rate >90%). (4) Introducing PCL / TPU shape memory material into the supercritical CO2 foamed PLGA / bioactive glass composite system, the shape memory polymer (PCL / TPU) enables the material to have body temperature responsive deformation ability. After implantation, it automatically triggers shape recovery under physiological environment, realizing precise fitting and long-term repair of bone defect morphology, adaptively fitting bone defect morphology, and solving the problem of intraoperative shaping. Detailed Implementation

[0025] The technical solution of the present invention will be illustrated below with specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0026] The preparation method of the PLGA / bioactive glass shape memory composite material in this invention includes the following steps: (1) The bioactive glass was modified with an aminosilane coupling agent to obtain the modified bioactive glass, wherein the modification ratio of the aminosilane coupling agent was 5-10% of the mass of the bioactive glass; the modified bioactive glass and PLGA were mixed and ball-milled at a mass ratio of 3:5-7, the speed was 200-300 rpm, and the time was 10-30 min to obtain a PLGA / BG mixture. (2) Mix the PLGA / BG mixture, NH2-PEG-PCL copolymer, and pore-forming agent PEG (average molecular weight 4000-6000), then add PCL / TPU shape memory material and mix thoroughly. The mass percentage of the PLGA / BG mixture and PCL / TPU shape memory material is 70-80%:20-30%. Based on the total mass of the PLGA / BG mixture and PCL / TPU shape memory material, the amount of NH2-PEG-PCL copolymer added is... The amount of pore-forming agent added is 12-18% of the total mass, and the amount of 5-10% of the total mass is pore-forming agent added. The mixture is placed in a sealed container, and supercritical CO2 is introduced. The initial temperature is 35-40℃, and the pressure is controlled at 20-25MPa. The pressure is maintained for 120-180min. Then, the pressure is maintained and the temperature is raised to 45-55℃ and maintained for 5-10min. After that, the pressure is first rapidly released to 10-15MPa, and the pressure release time is less than 2s. The pressure is maintained for 5-10min. Then, the pressure is slowly released to atmospheric pressure, and the pressure release time is 5-30s. (3) After cooling to room temperature, soak in hot water at 60-70℃ for 12-24 hours to remove the pore-forming agent. After drying at room temperature, freeze dry at -30℃ to -20℃ to obtain the composite material.

[0027] In a specific embodiment of the present invention, in step (1), an aminosilane coupling agent is used to modify the bioactive glass. The specific modification steps are as follows: bioactive glass powder with a particle size of 10-100 μm is immersed in an ethanol solution containing 0.3-0.7 wt% aminosilane coupling agent (γ-aminopropyltriethoxysilane), heated to 50-60℃ and reacted for 10-15 h, then washed and dried.

[0028] In a specific embodiment of the present invention, in step (1), the mass percentage of lactic acid to glycolic acid in PLGA (polylactic acid-glycolic acid copolymer) is 70-80%: 20-30%, the average molecular weight is 100,000-200,000 Da, and the powder particle size is 50-200 μm.

[0029] In a specific embodiment of the present invention, in step (2), the average molecular weight of the NH2-PEG-PCL copolymer is 1000-2000 Da.

[0030] In a specific embodiment of the present invention, step (2) of the preparation of PCL / TPU shape memory material specifically includes the following steps: after melting poly(ε-caprolactone diol) (average molecular weight of 3500), cooling to room temperature, adding hexamethylene diisocyanate and 2,4-toluene diisocyanate, heating to 65°C and stirring for 40 min; sequentially adding dimethyl carbonate, dibutyltin dilaurate and 1,4-butanediol, poly(ε-caprolactone diol), hexamethylene diisocyanate, 2,4-toluene diisocyanate and 1,4-butanediol. The molar ratio of 1,4-butanediol is 1:1:5:5; the amount of dimethyl carbonate added is 100% of the total mass of poly(ε-caprolactone diol), hexamethylene diisocyanate, 2,4-toluene diisocyanate, and 1,4-butanediol, and the amount of dibutyltin dilaurate added is 0.08% of the total mass; then the reaction is carried out at 65℃ for 4 hours, and then vacuum cured at 90℃. After cooling and pulverizing, PCL / TPU shape memory material is obtained with a particle size of 50-200μm and a shape recovery temperature of 35-40℃.

[0031] Example 1 (1) Bioactive glass modified with aminosilane coupling agent was obtained, wherein the bioactive glass had a particle size of 10-100 μm and an average particle size of 50 μm, and the modification ratio of aminosilane coupling agent was 7.4% of the bioactive glass mass; the modified bioactive glass was mixed with PLGA (lactic acid and glycolic acid in a mass ratio of 80%:20%, average molecular weight of 200,000 Da, powder particle size of 50-200 μm and average particle size of 100 μm) at a mass ratio of 3:6 and ball-milled at a speed of 200 rpm for 20 min to obtain a PLGA / BG mixture; (2) Mix the PLGA / BG mixture, NH2-PEG-PCL copolymer (average molecular weight of 2000 Da) and pore-forming agent PEG4000, and then add PCL / TPU shape memory material and mix evenly. The mass percentage of PLGA / BG mixture and PCL / TPU shape memory material is 80%:20%. Based on the total mass of PLGA / BG mixture and PCL / TPU shape memory material, the amount of NH2-PEG-PCL copolymer added is 7.5% of the total mass, and the amount of pore-forming agent added is 14% of the total mass. Place the mixture in a sealed container, introduce supercritical CO2, the initial temperature is 35℃, the pressure is controlled at 22MPa, and the pressure is maintained for 150min. Then maintain the pressure and raise the temperature to 45℃, and maintain the pressure for 6min. After that, first quickly depressurize to 15MPa, the depressurization time is less than 2s, maintain for 6min, and then slowly depressurize to atmospheric pressure, the depressurization time is 10s. (3) After cooling to room temperature, soak in 65℃ hot water for 16 hours to remove the pore-forming agent. After drying at room temperature, freeze dry at -20℃ to obtain the composite material.

[0032] Example 2 (1) Bioactive glass modified with aminosilane coupling agent was obtained, wherein the bioactive glass had a particle size of 10-100 μm and an average particle size of 50 μm, and the modification ratio of aminosilane coupling agent was 7.4% of the bioactive glass mass; the modified bioactive glass was mixed with PLGA (lactic acid and glycolic acid in a mass ratio of 80%:20%, average molecular weight of 200,000 Da, powder particle size of 50-200 μm and average particle size of 100 μm) at a mass ratio of 3:6 and ball-milled at a speed of 200 rpm for 20 min to obtain a PLGA / BG mixture; (2) Mix the PLGA / BG mixture, NH2-PEG-PCL copolymer (average molecular weight of 2000 Da) and pore-forming agent PEG4000, and then add PCL / TPU shape memory material and mix evenly. The mass percentage of PLGA / BG mixture and PCL / TPU shape memory material is 70%:30%. Based on the total mass of PLGA / BG mixture and PCL / TPU shape memory material, the amount of NH2-PEG-PCL copolymer added is 8.2% of the total mass, and the amount of pore-forming agent added is 16% of the total mass. Place the mixture in a sealed container, introduce supercritical CO2, the initial temperature is 35℃, the pressure is controlled at 22MPa, and the pressure is maintained for 150min. Then maintain the pressure and raise the temperature to 50℃, and maintain the pressure for 10min. After that, first quickly depressurize to 15MPa, the depressurization time is less than 2s, maintain for 10min, and then slowly depressurize to atmospheric pressure, the depressurization time is 10s. (3) After cooling to room temperature, soak in 65℃ hot water for 16 hours to remove the pore-forming agent. After drying at room temperature, freeze dry at -20℃ to obtain the composite material.

[0033] Example 3 (1) Bioactive glass modified with aminosilane coupling agent was obtained, wherein the bioactive glass had a particle size of 10-100 μm and an average particle size of 50 μm, and the modification ratio of aminosilane coupling agent was 8.8% of the bioactive glass mass; the modified bioactive glass was mixed with PLGA (lactic acid and glycolic acid in a mass ratio of 80%:20%, average molecular weight of 200,000 Da, powder particle size of 50-200 μm and average particle size of 100 μm) at a mass ratio of 3:7 and ball-milled at a speed of 200 rpm for 30 min to obtain a PLGA / BG mixture; (2) Mix the PLGA / BG mixture, NH2-PEG-PCL copolymer (average molecular weight of 2000 Da) and pore-forming agent PEG4000, and then add PCL / TPU shape memory material and mix evenly. The mass percentage of PLGA / BG mixture and PCL / TPU shape memory material is 75%:25%. Based on the total mass of PLGA / BG mixture and PCL / TPU shape memory material, the amount of NH2-PEG-PCL copolymer added is 7.5% of the total mass, and the amount of pore-forming agent added is 14% of the total mass. Place the mixture in a sealed container, introduce supercritical CO2, the initial temperature is 35℃, the pressure is controlled at 22MPa, and the pressure is maintained for 150min. Then maintain the pressure and raise the temperature to 45℃ and maintain the pressure for 6min. After that, first quickly depressurize to 15MPa, the depressurization time is less than 2s, maintain for 8min, and then slowly depressurize to atmospheric pressure, the depressurization time is 15s. (3) After cooling to room temperature, soak in 65℃ hot water for 16 hours to remove the pore-forming agent. After drying at room temperature, freeze dry at -20℃ to obtain the composite material.

[0034] Comparative Example 1 The difference from Example 1 is that no NH2-PEG-PCL copolymer was added.

[0035] (1) Bioactive glass modified with aminosilane coupling agent was obtained, wherein the bioactive glass had a particle size of 10-100 μm and an average particle size of 50 μm, and the modification ratio of aminosilane coupling agent was 7.4% of the bioactive glass mass; the modified bioactive glass was mixed with PLGA (lactic acid and glycolic acid in a mass ratio of 80%:20%, average molecular weight of 200,000 Da, powder particle size of 50-200 μm and average particle size of 100 μm) at a mass ratio of 3:6 and ball-milled at a speed of 200 rpm for 20 min to obtain a PLGA / BG mixture; (2) Mix the PLGA / BG mixture and the pore-forming agent PEG 4000, then add the PCL / TPU shape memory material and mix evenly. The mass percentage of the PLGA / BG mixture and the PCL / TPU shape memory material is 80%:20%. Based on the total mass of the PLGA / BG mixture and the PCL / TPU shape memory material, the amount of pore-forming agent added is 14% of the total mass. Place the mixture in a sealed container, introduce supercritical CO2, the initial temperature is 35℃, the pressure is controlled at 22MPa, and the pressure is maintained for 150min. Then maintain the pressure and raise the temperature to 45℃, and maintain the pressure for 6min. After that, first quickly depressurize to 15MPa, the depressurization time is less than 2s, maintain for 6min, and then slowly depressurize to atmospheric pressure, the depressurization time is 10s. (3) After cooling to room temperature, soak in 65℃ hot water for 16 hours to remove the pore-forming agent. After drying at room temperature, freeze dry at -20℃ to obtain the composite material.

[0036] Comparative Example 2 The difference from Example 1 is that the proportion of PLGA / BG mixture added is too high. (1) Bioactive glass modified with aminosilane coupling agent was obtained, wherein the bioactive glass had a particle size of 10-100 μm and an average particle size of 50 μm, and the modification ratio of aminosilane coupling agent was 7.4% of the bioactive glass mass; the modified bioactive glass was mixed with PLGA (lactic acid and glycolic acid in a mass ratio of 80%:20%, average molecular weight of 200,000 Da, powder particle size of 50-200 μm and average particle size of 100 μm) at a mass ratio of 3:6 and ball-milled at a speed of 200 rpm for 20 min to obtain a PLGA / BG mixture; (2) Mix the PLGA / BG mixture, NH2-PEG-PCL copolymer (average molecular weight of 2000 Da) and pore-forming agent PEG4000, and then add PCL / TPU shape memory material and mix evenly. The mass percentage of PLGA / BG mixture and PCL / TPU shape memory material is 90%:10%. Based on the total mass of PLGA / BG mixture and PCL / TPU shape memory material, the amount of NH2-PEG-PCL copolymer added is 7.5% of the total mass, and the amount of pore-forming agent added is 14% of the total mass. Place the mixture in a sealed container, introduce supercritical CO2, the initial temperature is 35℃, the pressure is controlled at 22MPa, and the pressure is maintained for 150min. Then maintain the pressure and raise the temperature to 45℃, and maintain the pressure for 6min. After that, first quickly depressurize to 15MPa, the depressurization time is less than 2s, maintain for 6min, and then slowly depressurize to atmospheric pressure, the depressurization time is 10s. (3) After cooling to room temperature, soak in 65℃ hot water for 16 hours to remove the pore-forming agent. After drying at room temperature, freeze dry at -20℃ to obtain the composite material.

[0037] Comparative Example 3 The difference from Example 1 is that no PEG pore-forming agent is added.

[0038] (1) Bioactive glass modified with aminosilane coupling agent was obtained, wherein the bioactive glass had a particle size of 10-100 μm and an average particle size of 50 μm, and the modification ratio of aminosilane coupling agent was 7.4% of the bioactive glass mass; the modified bioactive glass was mixed with PLGA (lactic acid and glycolic acid in a mass ratio of 80%:20%, average molecular weight of 200,000 Da, powder particle size of 50-200 μm and average particle size of 100 μm) at a mass ratio of 3:6 and ball-milled at a speed of 200 rpm for 20 min to obtain a PLGA / BG mixture; (2) Mix the PLGA / BG mixture and the NH2-PEG-PCL copolymer (average molecular weight of 2000 Da), then add the PCL / TPU shape memory material and mix evenly. The mass percentage of the PLGA / BG mixture and the PCL / TPU shape memory material is 80%:20%. Based on the total mass of the PLGA / BG mixture and the PCL / TPU shape memory material, the amount of NH2-PEG-PCL copolymer added is 7.5% of the total mass. Place the mixture in a sealed container, introduce supercritical CO2, the initial temperature is 35℃, the pressure is controlled at 22MPa, and the pressure is maintained for 150min. Then maintain the pressure and raise the temperature to 45℃, and maintain the pressure for 6min. After that, first quickly depressurize to 15MPa, the depressurization time is less than 2s, maintain for 6min, and then slowly depressurize to atmospheric pressure, the depressurization time is 10s. (3) After cooling to room temperature and drying, freeze-dry at -20℃ to obtain composite material.

[0039] Comparative Example 4 The difference from Example 1 is that no staged heating was performed during supercritical CO2 foaming.

[0040] (1) Bioactive glass modified with aminosilane coupling agent was obtained, wherein the bioactive glass had a particle size of 10-100 μm and an average particle size of 50 μm, and the modification ratio of aminosilane coupling agent was 7.4% of the bioactive glass mass; the modified bioactive glass was mixed with PLGA (lactic acid and glycolic acid in a mass ratio of 80%:20%, average molecular weight of 200,000 Da, powder particle size of 50-200 μm and average particle size of 100 μm) at a mass ratio of 3:6 and ball-milled at a speed of 200 rpm for 20 min to obtain a PLGA / BG mixture; (2) Mix the PLGA / BG mixture, NH2-PEG-PCL copolymer (average molecular weight of 2000 Da) and pore-forming agent PEG4000, and then add PCL / TPU shape memory material and mix evenly. The mass percentage of PLGA / BG mixture and PCL / TPU shape memory material is 80%:20%. Based on the total mass of PLGA / BG mixture and PCL / TPU shape memory material, the amount of NH2-PEG-PCL copolymer added is 7.5% of the total mass, and the amount of pore-forming agent added is 14% of the total mass. Place the mixture in a sealed container, introduce supercritical CO2, the initial temperature is 45℃, the pressure is controlled at 22MPa, and the pressure is maintained for 160min. Then, first quickly depressurize to 15MPa, the depressurization time is less than 2s, maintain for 6min, and then slowly depressurize to atmospheric pressure, the depressurization time is 10s. (3) After cooling to room temperature, soak in 65℃ hot water for 16 hours to remove the pore-forming agent. After drying at room temperature, freeze dry at -20℃ to obtain the composite material.

[0041] Comparative Example 5 The difference from Example 1 is that during supercritical CO2 foaming, the pressure is released directly and rapidly.

[0042] (1) Bioactive glass modified with aminosilane coupling agent was obtained, wherein the bioactive glass had a particle size of 10-100 μm and an average particle size of 50 μm, and the modification ratio of aminosilane coupling agent was 7.4% of the bioactive glass mass; the modified bioactive glass was mixed with PLGA (lactic acid and glycolic acid in a mass ratio of 80%:20%, average molecular weight of 200,000 Da, powder particle size of 50-200 μm and average particle size of 100 μm) at a mass ratio of 3:6 and ball-milled at a speed of 200 rpm for 20 min to obtain a PLGA / BG mixture; (2) Mix the PLGA / BG mixture, NH2-PEG-PCL copolymer (average molecular weight of 2000 Da) and pore-forming agent PEG4000, then add PCL / TPU shape memory material and mix evenly. The mass percentage of PLGA / BG mixture and PCL / TPU shape memory material is 80%:20%. Based on the total mass of PLGA / BG mixture and PCL / TPU shape memory material, the amount of NH2-PEG-PCL copolymer added is 7.5% of the total mass, and the amount of pore-forming agent added is 14% of the total mass. Place the mixture in a sealed container, introduce supercritical CO2, the initial temperature is 35℃, the pressure is controlled at 22MPa, and the pressure is maintained for 150min. Then maintain the pressure and raise the temperature to 45℃, and maintain the pressure for 6min. After that, quickly depressurize to atmospheric pressure, and the depressurization time is less than 2s. (3) After cooling to room temperature, soak in 65℃ hot water for 16 hours to remove the pore-forming agent. After drying at room temperature, freeze dry at -20℃ to obtain the composite material.

[0043] The composite materials prepared in Examples 1-3 and Comparative Examples 1-5 were tested for porosity, pore connectivity, and compressive strength. The test results are shown in Table 1. The shape recovery rate of the composite materials prepared in Examples 1-3 and Comparative Examples 1-5 was also tested. The composite materials were subjected to a heating treatment, compressed to 30% of their volume at 37°C, and then cooled to 20°C for shape fixation. The deformed composite materials were then placed in PBS buffer at 37°C for shape recovery. After standing for 10 minutes, the shape recovery rate was measured (calculated using the volume at the time of deformation fixation and the volume after shape recovery).

[0044] Table 1 Porosity / % Hole connectivity / % Shape recovery rate / % Compressive strength / MPa Example 1 75 63 93.5 5.7 Example 2 79 70 91.8 5.2 Example 3 73 66 92.2 6.1 Comparative Example 1 66 51 89.6 4.7 Comparative Example 2 83 76 81.9 5.5 Comparative Example 3 60 53 84.1 5.8 Comparative Example 4 57 48 88.5 5.3 Comparative Example 5 65 9 90.3 5.9 As shown in Table 1, in Comparative Example 1, the lack of NH2-PEG-PCL copolymer affected the compatibility and interfacial bonding between multiphase materials, and also impacted the porous structure of the composite material, especially the supercritical CO2 foaming process, thus affecting porosity, pore connectivity, and mechanical strength. In Comparative Example 2, the excessive addition of the PLGA / BG mixture resulted in significant tissue resistance affecting the shape recovery of the composite material, leading to a reduced shape recovery rate and preventing the composite material from adapting to bone defect morphology as a bone filler. In Comparative Example 3, the absence of PEG pore-forming agent resulted in a moderately interconnected pore structure during supercritical CO2 foaming, but the overall pore connectivity was low, preventing the composite material from exhibiting good osteogenic and angiogenic properties as a bone filler. Comparative Examples 4-5 all showed poor foaming results due to parameter adjustments during the supercritical CO2 foaming process. Specifically, the lack of staged heating during foaming prevented the supercritical CO2 from being phase-separated and enriched, reducing both porosity and pore connectivity. Rapid depressurization during depressurization resulted in the formation of only closed-cell structures, significantly reducing pore connectivity.

[0045] The above are merely preferred embodiments of the present invention and do not limit the patent scope of the present invention. Any equivalent structural or procedural transformations made using the present invention specification, or direct or indirect applications in other related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. A method for preparing a PLGA / bioactive glass shape memory composite material, characterized in that, Includes the following steps: (1) The bioactive glass was modified with an aminosilane coupling agent. The modified bioactive glass was mixed with PLGA and ball-milled to obtain a PLGA / BG mixture. (2) Mix PLGA / BG mixture, NH2-PEG-PCL copolymer and pore-forming agent, then add PCL / TPU shape memory material and mix. Place it in a sealed container, introduce supercritical CO2, the initial temperature is 35-40℃, the pressure is controlled at 20-25MPa, and the pressure is maintained for 120-180min. Then maintain the pressure and raise the temperature to 45-55℃, and maintain the pressure for 5-10min. After that, first quickly depressurize to 10-15MPa, the depressurization time is less than 2s, maintain for 5-10min, and then slowly depressurize to normal pressure, the depressurization time is 5-30s. (3) After cooling to room temperature, soak in hot water to remove the pore-forming agent, and freeze dry.

2. The method for preparing the PLGA / bioactive glass shape memory composite material according to claim 1, characterized in that, In step (1), the mass ratio of the modified bioactive glass to PLGA is 3:5-7; the modification ratio of the aminosilane coupling agent in the modified bioactive glass is 5-10% of the mass of the bioactive glass.

3. The method for preparing the PLGA / bioactive glass shape memory composite material according to claim 1 or 2, characterized in that, In step (1), the particle size of the bioactive glass is 10-100 μm; the particle size of the PLGA is 50-200 μm.

4. The method for preparing the PLGA / bioactive glass shape memory composite material according to claim 1, characterized in that, In step (2), the ratio of the PLGA / BG mixture to the PCL / TPU shape memory material is 70-80% by mass percentage: 20-30%.

5. The method for preparing the PLGA / bioactive glass shape memory composite material according to claim 1 or 4, characterized in that, In step (2), the amount of NH2-PEG-PCL copolymer added is 5-10% of the total mass of PLGA / BG mixture and PCL / TPU shape memory material; the average molecular weight of NH2-PEG-PCL copolymer is 1000-2000 Da.

6. The method for preparing the PLGA / bioactive glass shape memory composite material according to claim 1 or 4, characterized in that, In step (2), the amount of pore-forming agent added is 12-18% of the total mass of the PLGA / BG mixture and the PCL / TPU shape memory material; the pore-forming agent is PEG with an average molecular weight of 4000-6000.

7. The method for preparing the PLGA / bioactive glass shape memory composite material according to claim 1, characterized in that, In step (2), the shape recovery temperature of the PCL / TPU shape memory material is 35-40℃. It is prepared by using poly(ε-caprolactone diol) with an average molecular weight of 2000-3500 as the soft segment and the reaction product of isocyanate and 1,4-butanediol as the hard segment.

8. The method for preparing the PLGA / bioactive glass shape memory composite material according to claim 1, characterized in that, In step (3), the temperature of the hot water is 60-70℃ and the soaking time is 12-24h.

9. The method for preparing the PLGA / bioactive glass shape memory composite material according to claim 1, 7, or 8, characterized in that, In step (3), the freeze-drying temperature is -30°C to -20°C.

10. The application of a PLGA / bioactive glass shape memory composite material prepared by the preparation method according to any one of claims 1-9 in the field of bone repair.