Bone-integrative degradable silicone gel scaffold for treating bone nonunion and method of making same

Abstract

The application discloses a bone-integrative degradable silica gel support for treating bone nonunion and a preparation method thereof, and relates to the technical field of medical implant materials.The preparation method comprises the following steps: hydrogen-containing silicone oil and allyl glycidyl ether are subjected to a hydrosilylation reaction under the action of a platinum catalyst to generate silicone oil containing an epoxy group, then the epoxy group is subjected to ring-opening under the action of a catalyst to obtain silicone oil containing a phosphate group in a side chain; carboxyl-terminated polylactic acid-glycolic acid copolymer is mixed with the silicone oil containing the phosphate group in the side chain, and a condensation reaction is carried out under the action of a condensing agent and a catalyst to obtain a PLGA-P-PDMS-PLGA triblock copolymer; the triblock copolymer, a reactive diluent, a photoinitiator and inorganic reinforcing fillers are mixed to obtain 3D printing slurry; and the printing slurry is printed into a designed bone-integrative support according to set printing parameters by using a light-curing 3D printing technology.The application endows the material with intrinsic osteogenic activity, and realizes the unification of bioactivity, shape memory function and mechanical support.

Description

Technical Field

[0001] This invention relates to the field of medical implant materials technology, and in particular to an osteointegrative biodegradable silicone scaffold for treating bone nonunion and its preparation method. Background Technology

[0002] Fracture healing is a complex biological process that depends on adequate blood supply, a stable mechanical environment, and sufficient osteogenic activity. However, in clinical practice, some fracture patients develop healing failure, with atrophic nonunion being one of the most challenging types. It is characterized by severely impaired blood supply to the fracture ends, bone resorption and atrophy, and the formation of fibrous tissue septa lacking osteogenic potential, preventing the fracture ends from uniting spontaneously.

[0003] Currently, autologous bone grafting is considered the "gold standard" for treating atrophic nonunion. While it possesses the triple advantages of osteoconduction, osteoinduction, and osteogenic capacity, its availability is limited, and it can cause donor site complications (such as pain, infection, and nerve damage). Alternative materials such as allogeneic bone, calcium phosphate ceramics, calcium sulfate, and polymeric materials (such as PEEK) have addressed the availability issue to some extent, but their application in atrophic nonunion still has significant limitations, specifically in the following aspects:

[0004] 1. Insufficient biological properties of materials: Most synthetic materials (such as traditional calcium phosphate ceramics) only possess osteoconductive properties but lack the crucial osteoinductive properties, making it unable to actively recruit and induce mesenchymal stem cells to differentiate into osteoblasts, and difficult to initiate the biological environment of stiffened atrophic ends. More importantly, although conventional medical-grade silicone (polydimethylsiloxane) has excellent biocompatibility and elasticity, its inherent bioinertness and non-degradability make it unsuitable for the field of bone repair. It cannot integrate with bone tissue and will remain as a permanent foreign body.

[0005] 2. Mismatch in material mechanical properties: The mechanical properties of existing bone substitutes differ significantly from those of human bone. Ceramic materials such as hydroxyapatite are too hard and brittle, with an elastic modulus far exceeding that of cortical bone. This can easily lead to a "stress shielding" effect, hindering adaptive remodeling during bone healing and potentially causing internal fixation failure or refracture. Currently, there is a lack of an ideal material that can provide a suitable elastic modulus, mimic bone biomechanical behavior, and actively participate in bone integration.

[0006] 3. Insecure initial fixation: Atrophic nonunion is often accompanied by bone defects. Existing block or granular filler materials are difficult to achieve initial stability within the defect area after implantation. Micromovement easily occurs between them and the host bone interface, relying on external or internal fixation systems to provide full stability. However, the atrophic bone ends are often sparse, resulting in weakened holding force of internal fixation devices (such as screws), insecure fixation, and consequently hindering the ingrowth of new blood vessels and bone tissue, which is an important reason for treatment failure.

[0007] 4. Low degree of personalization: Traditional machining methods struggle to produce implants that perfectly match the complex morphology of three-dimensional bone defects. Morphological mismatch leads to gaps between the implant and the host bone, reducing the contact area, affecting bone conduction efficiency, and further exacerbating initial fixation instability.

[0008] In recent years, 3D printing technology has made it possible to manufacture personalized bone scaffolds, but its development is limited by the inherent defects of the materials themselves. In other words, even if a morphologically matched scaffold can be printed, if its core material lacks bioactivity, biodegradability, and suitable mechanical properties, and if the fixation problem is not solved, it will still not be able to effectively cure atrophic nonunion.

[0009] Therefore, there is an urgent need in this field for a novel material that combines bioactivity, tunable degradability, and bone-like elastic modulus, and can be molded into a personalized implant through advanced manufacturing technology that achieves immediate mechanical stability and long-term biointegration, in order to fundamentally overcome many bottlenecks in existing treatment methods. Therefore, designing an osteointegrative biodegradable silicone scaffold for the treatment of atrophic nonunion and its preparation method is both practically necessary and innovative. Summary of the Invention

[0010] In view of the above-mentioned shortcomings and deficiencies of the prior art, the present invention provides an osteointegrative biodegradable silicone scaffold for treating bone nonunion and its preparation method. Through molecular design at the material level and structural design at the structural level, the invention achieves the unity of bioactivity, shape memory function and mechanical support.

[0011] According to one aspect of the present invention, a method for preparing an osteointegrative biodegradable silicone scaffold for treating bone nonunion is provided, comprising: Step one, synthesizing silicone oil with phosphate ester group side chains: reacting hydrogen-containing silicone oil with allyl glycidyl ether in the presence of a platinum catalyst to generate silicone oil with epoxy group; subsequently reacting the silicone oil with phosphate group in the presence of a catalyst to open the epoxy group, thereby obtaining silicone oil P-PDMS with phosphate ester group side chains; Step two, preparing a biodegradable shape memory PLGA-P-PDMS-PLGA triblock copolymer: reacting carboxyl-terminated polylactic acid-glycolic acid copolymer PLGA with the silicone oil P-PDMS obtained in step one with phosphate ester group side chains. PDMS is mixed and undergoes a condensation reaction under the action of a condensing agent and a catalyst to obtain a PLGA-P-PDMS-PLGA triblock copolymer; Step 3, 3D printing slurry preparation: The PLGA-P-PDMS-PLGA triblock copolymer obtained in Step 2, reactive diluent, photoinitiator and inorganic reinforcing filler are mixed and stirred to obtain a uniform photocurable 3D printing slurry; Step 4, osseointegrated scaffold modeling: A three-dimensional model of a osseointegrated scaffold with a porous structure is designed using modeling software; Step 5, 3D printing: Using photocurable 3D printing technology, the printing slurry prepared in Step 3 is printed into the osseointegrated scaffold designed in Step 4 according to the set printing parameters.

[0012] Optionally, in step one, the hydrogen-containing silicone oil has a hydrogen content of 0.75% and a molecular weight of 10,000; the hydrosilylation reaction is carried out in toluene solvent, the platinum catalyst is an isopropanol solution of chloroplatinic acid with a platinum content of 50 ppm, the reaction temperature is 80°C, and the reaction time is 6 hours; in the ring-opening reaction, the molar ratio of epoxy group to phosphoric acid is 1:1.2, the ring-opening reaction temperature is 50°C, the reaction time is 8 hours, and the catalyst is triethylamine.

[0013] Optionally, in step two, the molar ratio of lactic acid to glycolic acid in the carboxyl-terminated polylactic acid-glycolic acid copolymer is 85:15, and the molecular weight Mn is 3000; the molar ratio of the carboxyl-terminated polylactic acid-glycolic acid copolymer to the silicone oil with phosphate ester groups in the side chain is 2.2:1; the condensation reaction is carried out in N,N-dimethylformamide solvent at a reaction temperature of 40°C for 24 hours; the condensing agent is N,N'-diisopropylcarbodiimide, and the catalyst is 4-dimethylaminopyridine.

[0014] Optionally, the PLGA-P-PDMS-PLGA triblock copolymer prepared in step two has a two-phase microstructure consisting of a stationary phase and a reversible phase. The reversible phase is composed of P-PDMS segments with a glass transition temperature below room temperature, which are in a highly elastic state at body temperature to provide flexibility and resilience. The stationary phase is composed of PLGA segments with a crystallization melting temperature or glass transition temperature above body temperature, which serve as physical crosslinking points to fix the temporary shape and control shape recovery under body temperature triggering.

[0015] Optionally, in step three, the reactive diluent is hydroxyethyl methacrylate; the photoinitiator is Irgacure 2959; the inorganic reinforcing filler is nano-hydroxyapatite with a particle size of 50 nm; and the component ratio by weight is: 50 parts PLGA-P-PDMS-PLGA triblock copolymer, 20 parts hydroxyethyl methacrylate, 1 part Irgacure 2959, and 30 parts nano-hydroxyapatite.

[0016] Optionally, in step four, the three-dimensional model of the osseointegrated scaffold has a radially gradient porous structure, including an inner layer with a pore size of 300 μm and an outer layer with a pore size of 600 μm, and the two ends of the scaffold are designed with spring-shaped fixing ends.

[0017] Optionally, in step five, a digital light processing bio-3D printer is used to print the shape, with the following printing parameters: layer thickness 30μm, exposure intensity 25mW / cm². 2 Each layer was exposed for 8 seconds, and the printing temperature was 25℃.

[0018] According to another aspect of the present invention, a bone-integrated biodegradable silicone scaffold prepared by the preparation method described above is provided.

[0019] Optionally, the shape memory training and in vivo anchoring of the osteointegrative biodegradable silicone scaffold for treating bone nonunion includes the following steps: Setting a permanent shape: Heating the osteointegrative scaffold to a temperature higher than the PLGA segment transition temperature softens the PLGA segments, and the material enters a highly elastic state. At this point, the shape of the scaffold is its permanent shape; Fixing a temporary shape: At the highly elastic temperature, an external force is applied to the spring-shaped fixing end of the scaffold to compress and deform it. While maintaining the external force, the scaffold is cooled to a temperature lower than the PLGA segment transition temperature, causing the PLGA segment movement to freeze and form physical cross-linking points, thereby fixing the compressed temporary shape; Shape recovery and anchoring: After the scaffold with the fixed temporary shape is implanted in the body, the PLGA segment movement ability is restored under the action of body temperature. Driven by the entropy elasticity of the P-PDMS segments, the scaffold automatically recovers to its permanent shape, achieving firm anchoring with bone tissue.

[0020] Optionally, in the step of setting the permanent shape, the support is heated to 65°C; in the step of fixing the temporary shape, the support is cooled to 0°C.

[0021] The beneficial effects of this invention are:

[0022] (1) This invention fundamentally changes the biological properties of silicone materials by performing molecular-level functionalization design and precise phosphate ester functionalization modification of the siloxane side chains, transforming them from traditional bioinert elastomers into advanced biomaterials with tunable degradability, excellent elasticity, and intrinsic osteogenic activity. During degradation, the material continuously releases beneficial osteogenic factors such as silicon ions and can efficiently promote osteoblast adhesion and differentiation through surface chemically bonded active groups (such as phosphate esters), thereby actively inducing bone regeneration and specifically solving the core problem of osteogenic capacity failure in atrophic nonunion areas. This is because traditional silicone has high Si-O bond energy and non-reactive side groups, making it difficult to participate in biochemical reactions. Ultimately, it is encapsulated by fibers in vivo, forming an isolation that prevents integration with bone tissue. This invention, through precise functionalization design of the molecular structure, replaces some methyl side groups with phosphate ester groups. Phosphate ester groups are negatively charged under physiological conditions and are efficient binding sites for calcium ions and various adhesion proteins. Moreover, phosphate ester groups are chemically similar to the inorganic components of bone. Secondly, PLGA is copolymerized with the silicone backbone as a hard segment. PLGA forms rigid regions that serve as physical crosslinking points, while the PDMS segments maintain flexibility, together determining the material's mechanical properties and shape memory effect. Furthermore, the negatively charged phosphate groups preferentially adsorb Ca. 2+ After local supersaturation, it reacts with PO4 3- The material combines to form amorphous calcium phosphate, which gradually transforms into a more crystalline bone-like apatite layer (Ca / P≈1.68), giving the material its osteoconductive potential.

[0023] (2) This invention utilizes 3D printing technology to prepare the above-mentioned active material into a personalized scaffold with a radial gradient porous structure. This design not only achieves immediate postoperative stability through the shape memory spring-shaped fixing end, but also guides bone tissue to grow in rapidly through the outer large-diameter channels, forming a "biological rivet" effect to achieve medium- and long-term biological fixation, providing a crucial stable mechanical environment for bone healing, and fundamentally overcoming the defects of traditional filling materials that are prone to loosening and displacement.

[0024] (3) The stent of this invention can be precisely customized according to the patient's CT data to achieve a perfect morphological fit to the bone defect and maximize bone conduction efficiency. At the same time, the material is biodegradable and can be replaced by new bone tissue, eliminating the risk of long-term foreign body residue. This solution organically combines personalized design, bioactivity, and firm fixation, greatly simplifying the surgical procedure and reducing the risk of postoperative infection and fixation failure, providing a safer, more effective, and reliable radical treatment option for atrophic nonunion. Attached Figure Description

[0025] The accompanying drawings, which are included to provide a further understanding of the invention and form part of this invention, illustrate exemplary embodiments of the invention and are used to explain the invention, but do not constitute an undue limitation of the invention. In the drawings:

[0026] Figure 1 This is a flowchart illustrating the preparation method of the osteointegrative biodegradable silicone scaffold used for treating bone nonunion in this invention.

[0027] Figure 2 This is a flowchart illustrating the preparation process of silicone oil containing epoxy groups and phosphate ester side groups in this invention.

[0028] Figure 3 This is a flowchart illustrating the preparation process of the biodegradable shape memory PLGA-P-PDMS-PLGA triblock copolymer in this invention.

[0029] Figure 4 This is a design drawing of the osseointegrated scaffold based on the shape memory effect in this invention;

[0030] Figure 5 This is a schematic diagram of the shape restoration of the osseointegration scaffold based on the shape memory effect in this invention;

[0031] In the diagram, 81: inner layer; 82: outer layer; 83: spring-shaped fixing end. Detailed Implementation

[0032] To enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present application, and not all of them. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present application. It should be noted that, unless otherwise specified, the embodiments and features in the embodiments of the present application can be combined with each other.

[0033] The terms “comprising” and “having”, and any variations thereof, in the specification and claims of this application are intended to cover non-exclusive inclusion, for example, a process, method, product, or apparatus that includes a series of steps or units is not necessarily limited to those steps or units that are explicitly listed, but may include other steps or units that are not explicitly listed or that are inherent to such process, method, product, or apparatus.

[0034] Example 1: This example provides a method for preparing an osteointegrative biodegradable silicone scaffold for treating bone nonunion, referring to... Figure 1This method combines molecular design, material synthesis, and advanced manufacturing technologies to prepare personalized bone repair scaffolds that possess bioactivity, biodegradability, and shape memory functions. The preparation method includes:

[0035] Step 1: Synthesis of silicone oil with phosphate ester groups in the side chain (P-PDMS):

[0036] Reference Figure 2 The reaction pathway shown first synthesizes a bioactive silicone oil-based material:

[0037] In a dry 1000mL three-necked flask, 100g of hydrogen-containing silicone oil (PHMS, hydrogen content 0.75%, molecular weight 10000) and 400mL of toluene were added as solvents. Then, allyl glycidyl ether (28g) and isopropanol solution of chloroplatinic acid (platinum content 50ppm) were added. Under nitrogen protection, the mixture was reacted at 80℃ for 6 hours to generate epoxy-containing silicone oil through hydrosilylation reaction.

[0038] This process utilizes the Si-H bonds on the side chains of hydrosilicone oil (PHMS) to undergo a hydrosilylation reaction with the carbon-carbon double bonds at the end of allyl glycidyl ether under the action of a platinum catalyst (chloroplatinic acid). This reaction covalently links the side chains containing active epoxy groups to the polysiloxane backbone via Si-C bonds. The epoxy ring has high reactivity and serves as a "handle" for further reaction with phosphoric acid. This method preserves the inherent properties of silicone, and the main chain remains a flexible Si-O-Si structure, ensuring the basic elasticity of the material.

[0039] The reaction system was then cooled to 50°C, and 85% phosphoric acid aqueous solution (epoxy group: phosphoric acid = 1:1.2) was slowly added dropwise. 0.5g of triethylamine was added as a catalyst, and the reaction was maintained at 50°C for 8 hours to allow the epoxy group to completely open the ring. After the reaction was completed, the solvent was removed by vacuum distillation, the product was precipitated three times with n-hexane, and dried under vacuum for 48 hours to obtain silicone oil (P-PDMS) with phosphate ester groups in the side chain.

[0040] When epoxy-containing silicone oil reacts with phosphoric acid, the P-OH group of the phosphoric acid attacks the epoxy ring, forming a phosphate ester bond. This phosphate ester group then connects to the siloxane side chain via a stable COP covalent bond, achieving intrinsic osteogenic activity: the phosphate ester group is an analogue of the inorganic components of bone. After implantation, it can efficiently induce the deposition of bone-like apatite and provide specific recognition signals for osteoblasts, fundamentally altering the bioinertness of silicone. Simultaneously, it can enhance interfacial integration: the phosphate ester group significantly improves the material's hydrophilicity, promoting protein adsorption and cell adhesion.

[0041] Step 2: Preparation of biodegradable shape memory PLGA-P-PDMS-PLGA triblock copolymer:

[0042] Reference Figure 3 The synthetic pathway shown demonstrates the preparation of smart materials with shape memory capabilities:

[0043] The carboxyl-terminated polylactic acid-glycolic acid copolymer (PLGA, LA:GA=85:15, Mn=3000) was mixed with the silicone oil (P-PDMS) with phosphate ester side chains obtained in step one at a molar ratio of 2.2:1. 300 mL of solvent N,N-dimethylformamide (DMF), condensing agent N,N'-diisopropylcarbodiimide (DIC), and catalyst 4-dimethylaminopyridine (DMAP) were added. After reacting at 40 °C for 24 hours, the reaction solution was poured into ice-cold methanol to precipitate, filtered, and vacuum dried to obtain the PLGA-P-PDMS-PLGA triblock copolymer.

[0044] This triblock copolymer, through precise molecular design, constructs a two-phase microstructure with a stationary phase and a reversible phase, which is the molecular basis of the shape memory effect. Reaction principle: Through a condensation reaction, PLGA with terminal carboxyl groups is linked to silicone oil containing phosphate ester groups in its side chains, forming a PLGA-P-PDMS-PLGA triblock copolymer. The core of its shape memory and degradation is: Reversible phase / soft segment: P-PDMS segments, whose glass transition temperature (Tg) is much lower than room temperature, are in a highly elastic state at body temperature, providing flexibility and resilience to the material. Stationary phase / hard segment: PLGA segments. PLGA is a semi-crystalline polymer with a crystallization melting temperature (Tm) or Tg higher than body temperature (e.g., 65°C). It acts as a physical crosslinking point, playing a decisive role in temporary shape fixation and recovery.

[0045] Step 3, Prepare 3D printing paste:

[0046] 50g of the PLA-P-PDMS-PLA triblock copolymer obtained in step 2 was mixed with 20g of reactive diluent (hydroxyethyl methacrylate) and 1g of photoinitiator (Irgacure 2959). 30g of nano-hydroxyapatite (nHA, particle size 50nm) was added as a reinforcing filler. The mixture was stirred at high speed using a planetary mixer for 2 hours to obtain a uniform photocurable 3D printing slurry with suitable viscosity.

[0047] Step 4: Modeling the osseointegrated scaffold;

[0048] A bone integration scaffold model was designed using 3D modeling software such as Cinema 4D, based on bionics and biomechanics principles. (Refer to...) Figure 4The structure shown employs a radial gradient porous design. The inner layer 81 and outer layer 82 form the radial gradient porous structure. The inner layer 81 has a pore diameter of 300 μm, primarily providing mechanical support, while the outer layer 82 has a pore diameter of 600 μm, designed to promote rapid bone ingrowth. The scaffold also features spring-like fixing ends 83 at both ends, providing excellent fixation capabilities. The porous structure was generated using the random field command in C4D software, and the porosity was adjusted by modifying the proportion of the random field.

[0049] Step 5: 3D printing to complete the shape;

[0050] Using a DLP (Digital Light Processing) high-precision bio-3D printer, with a layer thickness of 30μm and an exposure intensity of 25mW / cm², the results were obtained. 2 With an exposure time of 8 seconds per layer and a printing temperature of 25°C, the printing paste obtained in step three is printed into the osseointegrated scaffold designed in step four.

[0051] After the scaffold is fabricated, shape memory training is required to ensure its clinical applicability. The shape memory training process for the fabricated osseointegrated scaffold is as follows:

[0052] Step A (Setting the permanent shape): Heat the printed osseointegrated scaffold to 65°C (higher than the transition temperature of the PLGA segments). At this temperature, the PLGA segments have enhanced mobility and the material is in a highly elastic state.

[0053] Step B (Fix Temporary Shape): Apply external force to deform the spring-shaped fixation end of the osseointegration scaffold into a compressed state, and keep it under external force while cooling to 0°C (below the transition temperature of PLGA segments). The PLGA segments freeze, forming physical cross-linking points, thus fixing the temporary shape.

[0054] Step C (Shape Restoration and Anchoring): As Figure 5 When the temperature rises to 37°C (body temperature), the PLGA chain segments regain their mobility, and the material automatically recovers to its original permanent shape under entropy elastic drive, achieving firm anchoring. This scaffold fixation method based on shape memory recovery can greatly reduce surgical trauma.

[0055] This invention transforms silica gel from a bioinert material into a smart material with intrinsic osteogenic activity by functionalizing it with phosphate esters. The phosphate ester groups, as analogs of inorganic components of bone, can efficiently induce bone-like apatite deposition and provide specific recognition signals for osteoblasts, actively promoting bone regeneration. Simultaneously, the material continuously releases osteogenic factors such as silicon ions during degradation, addressing the core issue of weak osteogenic capacity in atrophic nonunion.

[0056] A bone integration scaffold model with a radially gradient porous structure was constructed using 3D printing. After implantation, shape memory effect-driven self-expansion enables immediate stabilization; the outer porous structure provides channels for blood vessel and bone tissue ingrowth, ultimately forming a "bio-rivet" for long-term biological fixation, providing an important stable environment for bone healing.

[0057] The scaffold can be customized based on the patient's CT data to achieve a perfect fit to the bone defect. The material is ultimately completely degradable and replaced by new bone tissue, eliminating the risk of long-term foreign body residue. This invention organically combines bioactivity, intelligent fixation, and personalized manufacturing, significantly simplifying the surgical procedure, reducing the risk of postoperative complications, and providing a safe, effective, and reliable radical solution for atrophic nonunion.

[0058] Example 2: To verify the degradation characteristics and biocompatibility of the osteointegrated biodegradable silicone scaffold in Example 1, a systematic in vitro degradation experiment was conducted in this example. The specific experimental methods and results are analyzed below:

[0059] The osteointegrated biodegradable silicone scaffold sample was weighed precisely, and its initial mass was denoted as W. o The samples were immersed in PBS buffer and placed in a constant temperature environment of 37°C to simulate the in vivo environment. Samples were removed at preset time points (0, 2, 4, 8, and 12 weeks), rinsed thoroughly with deionized water, vacuum dried, and then weighed to determine their current mass (W). t ), calculate the quality retention rate (%) = (W t / W o )×100%, and simultaneously, the ion concentration in the immersion solution (including silicon ions (Si)) was detected. 4+ ) and phosphate ions (PO4) 3- The concentration of the sample and the pH value changes were observed, and the experimental results are shown in Table 1 below.

[0060] Table 1: In vitro degradation performance data of materials

[0061] Degradation time (weeks) Quality retention rate (%) Silicon ion release concentration (ppm) Phosphate ion release concentration (ppm) pH value 0 100 0 0 7.41 2 94.23 2.5 5.8 7.38 4 86.88 5.2 11.5 7.32 8 68.52 8.8 18.2 7.28 12 49.37 12.1 23.5 7.16

[0062] Based on the above experimental data, the bone-integrated biodegradable silicone scaffold of the present invention possesses the following characteristics:

[0063] Controllable degradation performance: The material exhibited stable and controllable degradation characteristics during the 12-week experimental period. The mass retention rate showed a smooth downward trend, and the mass loss was smooth, eventually dropping to 49.37%. This indicates that the material did not disintegrate suddenly, which meets the requirements of ideal bone repair materials for degradation behavior.

[0064] Continuous release of bioactive factors: During the degradation process, the material continuously releases silicon ions and phosphate ions. These ions have been widely confirmed by existing research to effectively upregulate the expression of osteogenic genes, promote angiogenesis, and thus actively induce bone regeneration.

[0065] Favorable biological environment: Throughout the degradation cycle, the pH of the soaking solution remained within the physiologically stable range of 7.16 to 7.41, without any significant acidic shift. This result indicates that the degradation products of the material do not induce a significantly acidic environment, thus avoiding the risk of aseptic inflammation that may result from acid accumulation.

[0066] In summary, the osteointegrated biodegradable silicone scaffold provided by this invention has a controllable degradation rate and the ability to continuously release osteogenic active ions, which can maintain the stability of the physiological environment and meet the clinical requirements for bone repair materials.

[0067] The sequence numbers of the above embodiments of the present invention are for descriptive purposes only and do not represent the superiority or inferiority of the embodiments.

[0068] Those skilled in the art will understand that the purpose of this invention is to provide a relatively universal overall preparation process or technical principle, and to cover as many different applicable scenarios and conditions as possible (such as different raw material characteristics, production scale, product demand, etc.). Therefore, some specific operations can be flexibly adjusted according to the situation in actual implementation, as long as the expected or the same or similar technical effects as those in the embodiments of this invention can be achieved.

[0069] The steps in the method of this invention can be adjusted, combined, or deleted according to actual needs. The technical features can be combined arbitrarily. For the sake of brevity, not all possible combinations of the technical features in the embodiments are described. However, as long as the combinations of these technical features do not contradict each other, they should all be considered within the scope of this invention.

[0070] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing an osteointegrative biodegradable silicone scaffold for treating bone nonunion, characterized in that, include: Step 1: Synthesize silicone oil with phosphate ester groups in the side chain: Hydrogen-containing silicone oil and allyl glycidyl ether undergo a hydrosilylation reaction under the action of a platinum catalyst to generate silicone oil containing epoxy groups; subsequently, the silicone oil containing epoxy groups is reacted with phosphoric acid under the action of a catalyst to open the epoxy groups, thereby obtaining silicone oil P-PDMS with phosphate ester groups in the side chain. Step 2: Preparation of biodegradable shape memory PLGA-P-PDMS-PLGA triblock copolymer: The carboxyl-terminated polylactic acid-glycolic acid copolymer PLGA was mixed with the silicone oil P-PDMS with phosphate ester groups in the side chain obtained in step one, and a condensation reaction was carried out under the action of a condensing agent and a catalyst to obtain PLGA-P-PDMS-PLGA triblock copolymer. Step 3, Prepare 3D printing paste: The PLGA-P-PDMS-PLGA triblock copolymer obtained in step two, the reactive diluent, the photoinitiator and the inorganic reinforcing filler are mixed and stirred to prepare a uniform photocurable 3D printing slurry; Step 4, Bone Integration Scaffold Modeling: A three-dimensional model of a porous osseous scaffold was designed using modeling software. Step 5, 3D printing to complete the shape: Using photopolymer 3D printing technology, the printing paste obtained in step three is printed into the osseointegrated scaffold designed in step four, according to the set printing parameters.

2. The method for preparing an osteointegrative biodegradable silicone scaffold for treating bone nonunion according to claim 1, characterized in that, In step one, the hydrogen-containing silicone oil has a hydrogen content of 0.75% and a molecular weight of 10,000. The hydrosilylation reaction is carried out in toluene solvent, the platinum catalyst is an isopropanol solution of chloroplatinic acid, the platinum content is 50 ppm, the reaction temperature is 80°C, and the reaction time is 6 hours. In the ring-opening reaction, the molar ratio of epoxy group to phosphoric acid is 1:1.2, the ring-opening reaction temperature is 50℃, the reaction time is 8 hours, and the catalyst is triethylamine.

3. The method for preparing an osteointegrative biodegradable silicone scaffold for treating bone nonunion according to claim 1, characterized in that, In step two, the molar ratio of lactic acid to glycolic acid in the carboxyl-terminated polylactic acid-glycolic acid copolymer is 85:15, and the molecular weight Mn is 3000; the molar ratio of the carboxyl-terminated polylactic acid-glycolic acid copolymer to the silicone oil with phosphate ester groups in the side chain is 2.2:1; the condensation reaction is carried out in N,N-dimethylformamide solvent at a reaction temperature of 40°C for 24 hours; the condensing agent is N,N'-diisopropylcarbodiimide, and the catalyst is 4-dimethylaminopyridine.

4. The method for preparing an osteointegrative biodegradable silicone scaffold for treating bone nonunion according to claim 1, characterized in that, The PLGA-P-PDMS-PLGA triblock copolymer prepared in step two has a two-phase microstructure consisting of a stationary phase and a reversible phase. The reversible phase is composed of P-PDMS segments with a glass transition temperature below room temperature, which are in a highly elastic state at body temperature and are used to provide flexibility and recovery force. The stationary phase is composed of PLGA segments with a crystallization melting temperature or glass transition temperature above body temperature. As a physical crosslinking point, it is used to fix the temporary shape and control the shape recovery under body temperature triggering.

5. The method for preparing an osteointegrative biodegradable silicone scaffold for treating bone nonunion according to claim 1, characterized in that, In step three, the reactive diluent is hydroxyethyl methacrylate; the photoinitiator is Irgacure 2959; the inorganic reinforcing filler is nano-hydroxyapatite with a particle size of 50 nm; and the component ratio by weight is: 50 parts PLGA-P-PDMS-PLGA triblock copolymer, 20 parts hydroxyethyl methacrylate, 1 part Irgacure 2959, and 30 parts nano-hydroxyapatite.

6. The method for preparing an osteointegrative biodegradable silicone scaffold for treating bone nonunion according to claim 1, characterized in that, In step four, the three-dimensional model of the osseointegrated scaffold has a radially gradient porous structure, including an inner layer with a pore size of 300 μm and an outer layer with a pore size of 600 μm, and the two ends of the scaffold are designed with spring-shaped fixing ends.

7. The method for preparing an osteointegrative biodegradable silicone scaffold for treating bone nonunion according to claim 1, characterized in that, In step five, a digital light processing bio-3D printer is used to print the shape, with the following printing parameters: layer thickness 30μm, exposure intensity 25mW / cm². 2 Each layer was exposed for 8 seconds, and the printing temperature was 25℃.

8. An osteointegrative biodegradable silicone scaffold for treating nonunion, prepared by the method described in any one of claims 1 to 7.

9. The osteointegrative biodegradable silicone scaffold for treating bone nonunion according to claim 8, characterized in that, The shape memory training and in vivo anchoring of the osteointegrated biodegradable silicone scaffold includes the following steps: Setting a permanent shape: The osseointegrated scaffold is heated to a temperature higher than the PLGA segment transition temperature, which softens the PLGA segments and puts the material into a highly elastic state. At this point, the shape of the scaffold is its permanent shape. Fixing the temporary shape: At the high elastic temperature, an external force is applied to the spring-shaped fixing end of the stent to compress and deform it. While maintaining the external force, the stent is cooled to a temperature below the PLGA chain segment transition temperature, causing the PLGA chain segments to freeze and form physical cross-linking points, thereby fixing the compressed temporary shape. Shape restoration and anchoring: After the scaffold that has been temporarily fixed in shape is implanted into the body, the PLGA chain segment regains its mobility under the action of body temperature. Driven by the entropy elasticity of the P-PDMS chain segment, the scaffold automatically restores its permanent shape, achieving firm anchoring with bone tissue.

10. The osteointegrative biodegradable silicone scaffold for treating bone nonunion according to claim 9, characterized in that, In the step of setting the permanent shape, the support is heated to 65°C; in the step of fixing the temporary shape, the support is cooled to 0°C.

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