Skull prosthesis and preparation method thereof

Abstract

The invention discloses a skull restoration and a preparation method thereof. The skull restoration comprises a first induction layer, a first supporting layer, an isolation layer, a second supporting layer and a second induction layer which are sequentially arranged from the inner side to the outer side. The first induction layer and the second induction layer are respectively formed by a material at least comprising mineralized collagen, the first supporting layer and the second supporting layer are respectively formed by compounding a high polymer material and nano biological ceramic particles, and the isolation layer is formed by a degradable polymer material and is suitable for realizing physical separation between the first supporting layer and the second supporting layer before the degradable polymer material is degraded. After the degradable polymer material is degraded, a three-dimensional communicated pore channel is formed; the average pore size of the three-dimensional communicating pore channel is smaller than that of the first induction layer, the first supporting layer, the second supporting layer and the second induction layer. According to the technical scheme, the supporting performance and the function of promoting bone tissue regeneration are both considered, bone tissues on the two sides are effectively fused in the central area, and the risk of infection caused in the initial stage of implantation is avoided.

Description

Technical Field

[0001] This invention relates to the field of bone repair materials technology, and in particular to a cranial repair body and its preparation method. Background Technology

[0002] Cranioplasty is a surgical treatment for skull defects, typically caused by trauma, surgery, or disease. These defects deprive the brain tissue of its normal protective barrier, making it vulnerable to direct damage from external forces. Cranioplasty restores this protective function. Materials used in cranioplasty typically include autologous bone or artificial materials such as hydroxyapatite, polyaryletherketone, and titanium mesh. Materials that closely resemble autologous skull in terms of biocompatibility and mechanical properties, and possess high malleability, are generally chosen as the most advanced materials for cranioplasty.

[0003] Currently, cranioplasty material technology is mature. Among them, there is a cranioplasty that induces bone tissue regeneration. It uses a support layer formed by polyaryletherketone and other bioactive materials to make inner and outer induction layers. It is customized for the patient's defect site using 3D printing technology. It can simultaneously meet the requirements of mechanical strength and biocompatibility, and helps to induce bone tissue regeneration in the defect area. However, the aforementioned cranioplasty still has at least the following problems: First, the support layer formed by polyaryletherketone (PAK) is non-degradable and requires encapsulation by inner and outer induction layers. If the osteoinductive properties of the inner and outer induction layers are weak, the patient's recovery time will be longer. Second, if other biodegradable materials are used to replace the non-degradable PAK to form the support layer, the stability and reliability of the support provided are still relatively insufficient. Third, due to the non-degradability of the PAK support layer, it is difficult for the bone tissue of the two induction layers to fuse effectively, thus disrupting the overall continuity. Fourth, although the existing technology can alleviate the problems mentioned above in the third aspect to some extent by setting multiple mesh holes in the support layer, it still does not achieve a satisfactory effect. Moreover, the mesh holes allow direct penetration of bone tissue on both sides of the defect, which will also lead to competitive bone formation in the early stage of cranioplasty implantation, resulting in insufficient bone volume in the central region. Fifth, the presence of mesh holes may also lead to the risk of infection in the early stage of cranioplasty implantation (the mesh holes can be considered as an infection channel).

[0004] Therefore, how to develop a prosthesis that can meet the requirements of good mechanical strength and biocompatibility, better induce bone tissue regeneration in the skull defect area, effectively fuse the bone tissue on both sides in the central area, and avoid the risk of infection in the early stage of implantation, thereby improving the mechanical properties and biointegration performance of the skull repair area, is an urgent problem to be solved in this field. Summary of the Invention

[0005] The problem that this invention aims to solve is that existing cranial prostheses are difficult to balance support performance and bone regeneration, as well as to achieve effective fusion of the two sides of the bone tissue in the central region and avoid the risk of infection in the early stages of implantation.

[0006] To address the aforementioned problems, the present invention provides a cranial prosthesis comprising: a first induction layer, a first support layer, an isolation layer, a second support layer, and a second induction layer, arranged sequentially from the inner to the outer side; the first and second induction layers are both formed of materials comprising at least mineralized collagen, the first and second support layers are both formed of a composite of polymer materials and nano-bioceramic particles, and the isolation layer is formed of a biodegradable polymer material; the isolation layer is adapted to physically separate the first and second support layers before the biodegradable polymer material degrades, and to form three-dimensional interconnected channels after the biodegradable polymer material has completed degradation; the average pore size of the three-dimensional interconnected channels is smaller than the average pore size of the first induction layer, the first support layer, the second support layer, and the second induction layer, respectively.

[0007] Optionally, the pore sizes of the first induction layer and the first support layer decrease in a gradient from the inside to the isolation layer, and the pore sizes of the second induction layer and the second support layer decrease in a gradient from the outside to the isolation layer; the average pore size of the first support layer is smaller than the average pore size of the first induction layer, and the average pore size of the second support layer is smaller than the average pore size of the second induction layer.

[0008] Optionally, the materials forming the first induction layer and the second induction layer may also include at least one of hydroxyapatite and collagen.

[0009] Optionally, the materials forming the first induction layer and the second induction layer may further include at least one of growth factors and metal ions.

[0010] Optionally, the growth factor includes at least one of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β).

[0011] Optionally, the nano-bioceramic particles include at least one of nano-hydroxyapatite (n-HA), β-tricalcium phosphate, and silicate bioactive ceramics.

[0012] Optionally, the biodegradable polymer material is poly-ε-caprolactone (PCL), polylactic acid-glycolic acid copolymer (PLGA), or polytrimethylene carbonate (PTMC).

[0013] Optionally, the polymeric material includes at least one of polylactic acid (PLA) and polyethylene glycol (PEG).

[0014] Optionally, the average pore size of the three-dimensional connecting channel is 20–90 μm, and the average pore size of the first induction layer and the second induction layer is 200–400 μm.

[0015] Optionally, the thickness of the isolation layer is 0.2 to 0.5 mm; the thickness of the first induction layer and the second induction layer is 0.5 to 1.0 mm; and the thickness of the first support layer and the second support layer is 2 to 3 mm.

[0016] To address the aforementioned problems, the present invention also provides a method for preparing the above-mentioned cranioplasty, comprising: forming a corresponding three-dimensional model of the cranioplasty based on scanning data of the patient's cranioplasty defect, and importing it into a fused deposition modeling (FDM) 3D printing device; forming a first inducing layer on a specific mold using the FDM 3D printing device based on a first printing material comprising at least mineralized collagen; forming a first support layer covering the first inducing layer using the FDM 3D printing device based on a second printing material formed by dispersing nano-bioceramic particles in a polymer solution; forming an isolation layer covering the first support layer using the FDM 3D printing device based on a third printing material formed from a biodegradable polymer material; forming a second support layer covering the isolation layer using the second printing material using the FDM 3D printing device; and forming a second inducing layer covering the second support layer using the first printing material using the FDM 3D printing device, thereby forming the cranioplasty.

[0017] To address the aforementioned problems, the present invention also provides a method for preparing the above-mentioned cranioplasty, comprising: forming a corresponding three-dimensional model of the cranioplasty based on scanning data of the patient's cranioplasty defect, and importing it into a stereolithography 3D printing device; mixing a polymer material, nano-bioceramic particles, and a photoinitiator to form a photosensitive resin material; using the photosensitive resin material, forming a first support layer and a second support layer through the stereolithography 3D printing device; spraying a solution containing a biodegradable polymer material between the first support layer and the second support layer to form the isolation layer; and based on a prepared induction layer slurry containing at least mineralized collagen, forming a first induction layer on the inner side of the first support layer and a second induction layer on the outer side of the second support layer through the stereolithography 3D printing device to form the cranioplasty.

[0018] To address the aforementioned problems, the present invention also provides a method for preparing the above-mentioned cranioplasty, comprising: forming a corresponding three-dimensional model of the cranioplasty based on scanning data of the patient's cranioplasty defect; mixing polymer materials, nano-bioceramic particles, and plasticizer, and forming a support layer plate by injection molding; heating a biodegradable polymer material to a molten state to form a thin film; preparing an induction layer gel comprising at least mineralized collagen; cutting and carving the support layer plate using CNC machining equipment according to the three-dimensional model of the cranioplasty to form a first support layer and a second support layer; placing the thin film between the first support layer and the second support layer, and bonding it tightly with the first support layer and the second support layer by hot pressing; injecting the induction layer gel into the inner side of the first support layer to form a first induction layer, and injecting it into the outer side of the second support layer to form a second induction layer; and placing the assembly comprising the first induction layer, the first support layer, the isolation layer, the second support layer, and the second induction layer in a vacuum drying oven for drying treatment to form the cranioplasty.

[0019] Compared with the prior art, the technical solution of the present invention has at least the following advantages:

[0020] 1. Technical Effects

[0021] (1) Optimize mechanical and biological properties

[0022] Existing cranioplasty scaffolds struggle to balance support performance with bone regeneration. The cranioplasty with a double-layer support structure, formed from biodegradable materials (preferably polylactic acid composite hydroxyapatite), provides stable and reliable mechanical support. Furthermore, by placing a biodegradable isolation layer between the two support layers, it serves to provide initial support and isolation, prevent mechanical interference (such as friction between the two support layers, structural interference, and stress concentration), control bone ingrowth rhythm, and block early infection pathways. As the isolation layer gradually degrades, it forms a three-dimensional interconnected structure, promoting effective fusion of bone tissue on both sides and improving repair quality and mechanical continuity.

[0023] (2) Gradient-progressive aperture structure

[0024] By making the pore sizes of the first and second induction layers on the inner and outer sides decrease in a gradient from the inner and outer sides to the isolation layer, the osteoinductive properties of the inner and outer induction layers can be enhanced, better enabling the ingrowth of bone tissue from both sides into the central region and forming effective fusion in the central region.

[0025] (3) Furthermore, by adding metal ions or growth factors to the first induction layer and the second induction layer, the bioactivity and osteoinductive properties are significantly improved, and the synergistic optimization of mechanical and biological properties is better achieved, providing a more ideal technical solution for cranial repair.

[0026] The technical solution of this invention solves the core problem of "insufficient support" in biodegradable systems by using a mineralized collagen composite "double support layer + isolation layer" structure, a gradient pore size structure, and AI process control. For the first time, it enables fully biodegradable cranial repair materials to achieve clinically usable levels in terms of both mechanical strength and osseointegration.

[0027] 2. Social impact

[0028] Traditional cranioplasty materials suffer from poor biocompatibility and weak bone integration, leading to postoperative rejection and impacting recovery, thus reducing quality of life. This patented scaffold, with its excellent biocompatibility, effectively reduces the risk of rejection; its superior osteoinductive and osteoconductive properties promote new bone growth and bone tissue integration, accelerating the cranioplasty process and enabling patients to return to normal life more quickly. It also reduces the social burden on healthcare: Existing repair materials may lead to postoperative complications such as infection and the need for secondary surgery due to repair failure, increasing patient suffering and consuming social healthcare resources. The reliable performance of this patented scaffold reduces the incidence of complications, minimizes waste of medical resources, alleviates the overall social healthcare burden, and allows limited medical resources to serve more patients.

[0029] 3. Economic effects

[0030] Reduced Medical Costs: The cranial prosthesis described in this application, with its stability and excellent repair effect, can reduce the number of follow-up visits and the probability of secondary surgery for patients, thereby lowering their overall medical expenses. Simultaneously, medical institutions can also reduce medical costs and improve operational efficiency due to fewer complications. Promoted Industrial Development: The 3D printing technology and new material applications involved in this application inject new vitality into the medical device industry, attracting more investment and R&D resources to this field. Around the patented technology, a complete industrial chain can be formed, from material research and development and 3D printing equipment manufacturing to product production and sales, creating more employment opportunities and driving economic growth in related industries. Attached Figure Description

[0031] Figure 1 This is a schematic diagram of the macroscopic structure of the cranial prosthesis provided in the embodiments of the present invention;

[0032] Figure 2 These are physical images of the inducing layer, support layer, and isolation layer of Embodiment 1 of the present invention;

[0033] Figure 3 This is a schematic diagram of the micropore size of the inducing layer observed by scanning electron microscopy in Embodiment 1 of the present invention;

[0034] Figure 4 This is a schematic diagram of the microstructure of the support layer in Embodiment 1 of the present invention;

[0035] Figure 5 This is a schematic diagram of the microstructure of the isolation layer before and after degradation in Embodiment 1 of the present invention. Detailed Implementation

[0036] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0037] like Figure 1 As shown, in an embodiment of the present invention, the provided cranial repair body includes: a first induction layer 11, a first support layer 21, an isolation layer 3, a second support layer 22, and a second induction layer 12 arranged sequentially from the inside to the outside; the first induction layer 11 and the second induction layer 12 are both formed of materials including at least mineralized collagen, the first support layer 21 and the second support layer 22 are both formed of polymer materials and nano-bioceramic particles, and the isolation layer 3 is formed of a biodegradable polymer material; the isolation layer 3 is adapted to physically separate the first support layer 21 and the second support layer 22 before the biodegradable polymer material degrades, and to form three-dimensional interconnected channels after the biodegradable polymer material has completed degradation. Figure 1 (not shown in the image); the average pore size of the three-dimensional connecting channels is smaller than the average pore size of the first induction layer 11, the first support layer 21, the second support layer 22, and the second induction layer 12, respectively.

[0038] In this embodiment, the pore sizes of the first induction layer 11 and the first support layer 21 decrease gradually from the inner side to the isolation layer 3, while the pore sizes of the second induction layer 12 and the second support layer 22 decrease gradually from the outer side to the isolation layer 3. The average pore size of the first support layer 21 is smaller than the average pore size of the first induction layer, and the average pore size of the second support layer is smaller than the average pore size of the second induction layer. By making the pore sizes of the first induction layer 11 and the second induction layer 12 on both the inner and outer sides decrease gradually from the inner and outer sides to the isolation layer 3, the resulting gradient pore size structure can enhance the osteoinductive properties of the inner and outer induction layers, better control the ingrowth of bone tissue from both sides into the central region, and achieve effective fusion in the central region.

[0039] In this embodiment, the average pore size of the three-dimensional interconnected channels formed after the degradation of the isolation layer 3 is 20-90 μm, which is used to regulate the cross-layer growth of bone tissue and prevent the invasion of fibrous tissue. In other embodiments, the pore size can also be adjusted to 10-120 μm according to the repair site, while still satisfying the biomimetic gradient relationship that the pore size of the isolation layer 3 is smaller than the pore sizes of the adjacent layers (first induction layer 11, first support layer 21, second induction layer 12, second support layer 22).

[0040] In specific implementation, the gradient decreasing distribution can be achieved through various process means such as zoned freezing temperature control, layered printing or phase separation induction. Its pore size gradually decreases from 200 to 400 μm in the first induction layer 11 and the second induction layer 12 to 20 to 90 μm in the isolation layer 3, so as to achieve bidirectional ingrowth of bone tissue and fusion with the middle layer.

[0041] In this embodiment, the materials forming the first induction layer 11 and the second induction layer 12 may include, in addition to mineralized adhesive raw materials, at least one of hydroxyapatite and collagen.

[0042] The materials forming the first induction layer 11 and the second induction layer 12 may further include at least one of growth factors and metal ions. The growth factors may include at least one of bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β). The metal ions may be at least one of ions such as strontium, magnesium, selenium, silicon, copper, iron, manganese, zinc, titanium, and silver. By adding metal ions and / or growth factors to the first induction layer 11 and the second induction layer 12, the bioactivity and osteoinductive properties of the inner induction layer are significantly improved, enabling more effective promotion of new bone formation and overcoming the limitations of traditional cranioplasty materials in promoting bone tissue regeneration.

[0043] In this embodiment, the various components (mineralized collagen, hydroxyapatite, collagen, metal ions or growth factors) in the first induction layer 11 and the second induction layer 12 work synergistically to promote the regeneration and repair of bone tissue.

[0044] The nano-bioceramic particles in the first support layer 21 and the second support layer 22 may include at least one of nano-hydroxyapatite (n-HA), β-tricalcium phosphate, and silicate bioactive ceramics, with nano-hydroxyapatite being preferred. The polymer material may include at least one of polylactic acid (PLA) and polyethylene glycol (PEG). In specific implementations, the first support layer 21 and the second support layer 22 can be formed by combining nano-hydroxyapatite with polylactic acid to form a composite material. By employing a polylactic acid-hydroxyapatite composite material, the first support layer 21 and the second support layer 22 fully combine the degradability and mechanical strength of polylactic acid with the biocompatibility and osteoconductivity of hydroxyapatite, providing reliable mechanical support and a favorable biological environment for cranioplasty.

[0045] In this embodiment, a good synergistic effect is also formed between the support layer (first support layer 21, second support layer 22) and the induction layer (first induction layer 11, second induction layer 12). The support layer provides stable mechanical support for the induction layer, while the induction layer promotes the integration of the support layer with the surrounding bone tissue, thereby achieving optimization of the cranial repair scaffold in terms of mechanical and biological properties.

[0046] The biodegradable polymer material in the isolation layer 3 can be polycaprolactone (PCL), polylactic acid-glycolic acid copolymer (PLGA), or polytrimethylene carbonate (PTMC). Depending on the different cranial prosthesis forming process, a suitable biodegradable polymer material can be selected.

[0047] In practice, the thickness range of each layer is determined according to the proportion of the natural skull tissue, so that the total thickness of the skull prosthesis is 6±1mm, which can meet the structural matching and osteogenesis requirements of local skull defects. For example, the thickness of the isolation layer 3 is 0.2-0.5mm; the thickness of the first induction layer 11 and the second induction layer 12 is 0.5-1.0mm; and the thickness of the first support layer 21 and the second support layer 22 is 2-3mm.

[0048] It is important to note that in the technical solution of this invention, a biodegradable isolation layer 3 with a thickness of 0.2 to 0.5 mm is provided between the support layers of the double-layer polylactic acid composite hydroxyapatite. This layer physically separates the first support layer 21 and the second support layer 22 in the early stages of implantation of the cranioplasty, preventing mutual friction and wear (when the stent is subjected to mechanical impact or shear, without an independent isolation layer, microscopic slippage and friction will occur between the two support layers, affecting the overall stability. With prolonged use, this interface friction may also lead to local pulverization or delamination), structural interference, and stress concentration, thus ensuring the structural stability of the cranioplasty; at the same time, it blocks the direct connection between the bone tissue on both sides of the defect, avoiding insufficient bone volume in the central region caused by early competitive bone formation. Over time, the biodegradable isolation layer 3 gradually degrades, breaking down into non-toxic small molecule products within 3-6 months post-implantation. The space between the two support layers gradually connects, forming three-dimensional interconnected channels, which facilitates bone ingrowth and integration. This allows for the fusion of bilateral new bone tissue in the central region, resulting in a dense, continuous bone plate structure. This further enhances the repair effect of the cranial prosthesis, achieving a dual improvement in both the mechanical and biointegration properties of the cranial repair area. It is conceivable that without the isolation layer 3, the two support layers would exhibit different stress concentrations and deformation patterns under cranial loads. Particularly between the outer layer (primarily responsible for mechanical protection) and the inner layer (in contact with bone and requiring a well-defined porous structure to promote osteogenesis), the difference in mechanical modulus would be significant. This difference would cause uneven stress transmission, leading to premature collapse of the inner layer or excessive load on the outer layer, resulting in structural failure or environmental degradation induced by the inner layer.

[0049] The aforementioned cranial prosthesis can be fabricated using fused deposition modeling (FDM) or stereolithography (SLA) techniques. The specific fabrication steps are as follows:

[0050] (1) Material preparation:

[0051] Preparation of polylactic acid composite hydroxyapatite material: Polylactic acid particles and hydroxyapatite powder are mixed in a certain proportion and prepared into a uniform polylactic acid composite hydroxyapatite raw material by melt blending and other methods, which is used for 3D printing the first support layer and the second support layer.

[0052] Preparation of inducing layer materials: Mineralized collagen, hydroxyapatite, and collagen are dissolved or dispersed in a suitable solvent in a certain proportion to form a uniform mixed solution; then, an appropriate amount of metal ions or growth factors are added as needed, and the mixture is stirred evenly to obtain the printing materials for the first and second inducing layers.

[0053] Prepare materials for the biodegradable isolation layer: Select suitable biodegradable polymer materials (such as polycaprolactone) and make them into filaments or powders suitable for 3D printing.

[0054] (2) 3D printing process:

[0055] Using a professional 3D printer, a precise three-dimensional model of the skull repair scaffold was designed and constructed based on CT scan data of the patient's skull defect. First, the 3D printer layer-by-layer induction layer material was printed onto a specific mold to form the first induction layer structure. Next, a layer of polylactic acid (PLA) composite hydroxyapatite material was printed onto the first induction layer to form the first support layer, followed by a layer of biodegradable insulating material to form the insulating layer. Then, PLA composite hydroxyapatite material was printed layer-by-layer onto the biodegradable insulating layer to form the second support layer. Finally, the second support layer was covered with the induction layer material to form the second induction layer, thus obtaining a complete double-layered PLA composite hydroxyapatite skull repair scaffold.

[0056] (3) Post-processing:

[0057] The printed skull prosthesis scaffold undergoes post-processing operations such as cleaning and drying to remove residual solvents and impurities from its surface. If necessary, the scaffold can be sterilized to meet clinical requirements. This is a standard technique in the field and will not be described in detail here.

[0058] The present invention specifically provides three methods for preparing the above-mentioned cranial prosthesis.

[0059] The first preparation method involves: forming a three-dimensional model of a cranial prosthesis based on scanning data of the patient's skull defect, and importing it into a fused deposition modeling (FDM) 3D printing device; forming a first inducing layer on a specific mold using a first printing material containing at least mineralized collagen, and using the FDM 3D printing device; forming a first support layer covering the first inducing layer using a second printing material formed by dispersing nano-bioceramic particles in a polymer solution, and using the FDM 3D printing device; forming an isolation layer covering the first support layer using a third printing material formed from a biodegradable polymer material, and using the FDM 3D printing device; forming a second support layer covering the isolation layer using the second printing material, and forming a second inducing layer covering the second support layer using the first printing material, thus forming the cranial prosthesis.

[0060] The second preparation method involves: forming a three-dimensional model of the cranial prosthesis based on scanning data of the patient's skull defect, and importing it into a stereolithography 3D printing device; mixing polymer materials, nano-bioceramic particles, and a photoinitiator to form a photosensitive resin material; using the photosensitive resin material, forming a first support layer and a second support layer through the stereolithography 3D printing device; spraying a solution containing a biodegradable polymer material between the first support layer and the second support layer to form the isolation layer; and forming a first induction layer on the inner side of the first support layer and a second induction layer on the outer side of the second support layer, respectively, based on a prepared induction layer slurry containing at least mineralized collagen, thus forming the cranial prosthesis.

[0061] The third preparation method involves: 1) Creating a three-dimensional model of the cranial prosthesis based on scan data of the patient's skull defect; 2) Mixing polymer materials, nano-bioceramic particles, and plasticizers, and molding them into a support layer plate using an injection molding machine; 3) Heating a biodegradable polymer material to a molten state to form a thin film; 4) Formulating an induction layer gel comprising at least mineralized collagen; 5) Cutting and carving the support layer plate using CNC machining equipment according to the three-dimensional model of the cranial prosthesis to form the first support layer and the second support layer; 6) Placing the thin film between the first and second support layers and using a hot-pressing process to tightly bond it to the first and second support layers; 7) Injecting the induction layer gel into the inner side of the first support layer to form the first induction layer, and into the outer side of the second support layer to form the second induction layer; 8) Drying the assembly containing the first induction layer, the first support layer, the isolation layer, the second support layer, and the second induction layer in a vacuum drying oven to form the cranial prosthesis.

[0062] The following specific examples illustrate the actual implementation of the above-mentioned method for preparing the skull prosthesis:

[0063] Example 1 (3D printing fabrication process based on fused deposition modeling):

[0064] Step S101: Polylactic acid particles and nano-hydroxyapatite powder are mixed in a mass ratio of 7:3 and melt-blended at 180°C using a twin-screw extruder to obtain polylactic acid composite hydroxyapatite raw material, which is then made into filament material for 3D printing the first and second support layers.

[0065] In step S102, mineralized collagen (concentration of 10 mg / mL) and hydroxyapatite (concentration of 5 mg / mL) are dissolved in acetic acid solution and stirred until homogeneous. Then, bone morphogenetic protein (BMP) at a concentration of 0.1 mg / mL is added to obtain printing materials for the inner induction layer (first induction layer) and the outer induction layer (second induction layer).

[0066] Step S103, Material preparation for the biodegradable isolation layer: Select polycaprolactone and make it into filament material for 3D printing the biodegradable isolation layer;

[0067] Step S104: Based on the CT scan data of the patient's skull defect, design an accurate three-dimensional model of the skull repair scaffold and import it into the 3D printer.

[0068] Step S105: Load the material suitable for forming the induction layer into the corresponding barrel of the 3D printer, and set the printing parameters: printing temperature is 60℃. The material suitable for forming the induction layer is printed layer by layer onto a specific mold by the 3D printer to form the first induction layer structure;

[0069] Step S106: Load polylactic acid composite hydroxyapatite filament material into the barrel, set the printing temperature to 210℃, and print a support layer (first support layer) on the first induction layer. The thickness of the first support layer is 3mm.

[0070] Step S107: Load polycaprolactone filament material into the barrel, set the printing temperature to 180℃, and print a 0.2mm thick biodegradable isolation layer on the printed first support layer.

[0071] In step S108, a support layer (second support layer) is printed on the isolation layer under the same conditions as in step S106, thereby obtaining a complete double-layer supported polylactic acid composite hydroxyapatite skull repair scaffold.

[0072] Step S109: Soak the printed bracket in deionized water for 24 hours to remove residual acetic acid solution on the surface, and then dry it in an oven at 60°C for 12 hours.

[0073] Step S110: Finally, place the stent into an ethylene oxide sterilizer for sterilization and set aside for later use.

[0074] The physical examples of the induction layer (first induction layer, second induction layer), support layer (first support layer, second support layer), and isolation layer formed in this embodiment are as follows: Figure 2 As shown in the figure, from left to right, the layers are the induction layer, the support layer, and the isolation layer.

[0075] Figure 3 This is a schematic diagram of the microscopic pore size of the induction layer observed by scanning electron microscopy in this embodiment. It can be seen that the average pore size of the induction layer is relatively large, which can have better bone induction properties, thereby better controlling the ingrowth of bone tissue from both sides into the central region. Figure 4 This is a schematic diagram of the microstructure of the support layer in this embodiment. The support layer has a small average pore size, which can provide stable and reliable mechanical support for the induction layer. Figure 5This is a schematic diagram of the microstructure of the isolation layer before and after degradation in this embodiment. From left to right, the diagram shows the microstructure before degradation and the microstructure after degradation. It can be seen that the isolation layer before degradation is relatively dense, which can isolate the two support layers from each other, prevent mechanical interference caused by friction between the two support layers, structural interference and stress concentration, control the bone ingrowth rhythm and block the early infection channel. The isolation layer after degradation forms a three-dimensional connected structure, which can promote the effective fusion of bone tissue on both sides and improve the repair quality and mechanical continuity.

[0076] Example 2 (3D Printing Fabrication Process Based on Stereolithography (SLA) Technology)

[0077] Step S201: Mix polylactic acid and hydroxyapatite powder at a mass ratio of 7:3, add 1% fluoroborate photoinitiator, and ultrasonically disperse the mixture for 30 minutes to obtain a uniform support layer photosensitive resin.

[0078] Step S202: Polylactic acid-glycolic acid copolymer (PLGA) is selected as the biodegradable separator material. PLGA is dissolved in dichloromethane to prepare a 10% (w / w) solution.

[0079] Step S203: Mineralized collagen and hydroxyapatite are mixed in a mass ratio of 3:2, and an appropriate amount of disodium hydrogen phosphate solution is added to make the phosphate ion concentration reach 3 mmol / L.

[0080] Step S204: Add bone morphogenetic protein-2 (BMP-2) at a mass fraction of 0.05% as a growth factor. After thorough mixing, prepare the induction layer slurry;

[0081] Step S205, Model Design: Same as Example 1;

[0082] Step S206: Pour the photosensitive resin for the support layer into the resin tank of the SLA printer. Set the laser power and the support layer thickness to 2mm. Print the inner and outer support layers one by one according to the designed model;

[0083] Step S207: Remove the printed support layer from the printer and use a spray gun to evenly spray the PLGA solution between the two support layers to form a 0.3mm thick isolation layer (degradable).

[0084] Step S208: Pour the induction layer slurry into the SLA printer, set the laser power to 80mW (60-100mW), the scanning speed to 400mm / s (300-450mm / s), the grid pitch to 120μm (100-140μm), and the single-layer thickness to 50μm (40-60μm). Print the first induction layer inside the first support layer and the second induction layer outside the second support layer, with a total thickness of 0.8mm (16 layers). After printing, use "10mW / cm" as the printing pressure. 2 Post-curing is performed for 10 minutes to ensure that the interlayer bonding strength and dimensional accuracy meet the above quality control indicators.

[0085] Step S209: After printing, place the skull prosthesis under a UV lamp for secondary curing for 1 hour to improve its curing degree; then clean the prosthesis with deionized water to remove surface impurities.

[0086] Example 3 (Preparation of a skull prosthesis with optimized structure and thickness)

[0087] Step S301: Polylactic acid (PLA) and hydroxyapatite (HA) are mixed at a mass ratio of 7:3, and 5% triethyl citrate is added as a plasticizer; the mixture is mixed evenly in a high-speed mixer, and then the support layer sheet is formed by injection molding at 190°C.

[0088] Step S302: Select polytrimethylene carbonate (PTMC) as a suitable material for forming a biodegradable isolation layer; heat PTMC to a molten state to form a film with a thickness of 0.4 mm;

[0089] Step S303: Mix mineralized collagen and hydroxyapatite in a mass ratio of 3:2, add an appropriate amount of sodium bicarbonate solution, and adjust the pH value to 8.

[0090] Step S304 involves simultaneously doping with zinc ions at a mass fraction of 0.15%. After thorough mixing, an induced layer gel is prepared.

[0091] Step S305, Model Design: Same as Example 1;

[0092] Step S306: According to the designed model, use CNC machining equipment to cut and carve the support layer plate to make inner and outer support layers with a thickness of 5mm respectively.

[0093] Step S307: Place the PTMC film between the two support layers and use a hot pressing process to make it tightly bonded to the two support layers. The hot pressing temperature is 50°C, the pressure is 5MPa, and the process is maintained for 10 minutes.

[0094] Step S308: Inject the induction layer gel into the inner and outer sides of the two support layers respectively to form two induction layers (i.e., the first induction layer and the second induction layer) with a thickness of 1.2 mm.

[0095] Step S309: The assembly comprising the first induction layer, the first support layer, the isolation layer, the second support layer and the second induction layer is placed in a vacuum drying oven and dried at 40°C for 48 hours to remove excess moisture; then the surface of the skull repair is subjected to plasma treatment to improve its hydrophilicity and biocompatibility.

[0096] The following are the experimental data for each of the above embodiments:

[0097] Table 1: Comparison of data from various embodiments of the present invention and comparative examples

[0098]

[0099] Based on the experimental results above, the three-layer structure exhibits a stable gradient of decreasing average pore size and increasing porosity in the direction of "inducing layer → supporting layer → isolation layer" (represented by Example 2: 243.14 μm → 97.24 μm → 31.85 μm; 64.42% → 69.31% → 84.36%). This ensures that the large pores in the outer and inner inducing layers facilitate osteogenic / vascular ingrowth, while the small pores in the middle isolation layer (31.85–86.92 μm, falling within the target range of 20–90 μm for the preferred average pore size of the three-dimensional connecting channels mentioned in the claims) allow for better ossification / vascular ingrowth. It effectively inhibits the initial translayer communication and potential infection pathways; at the same time, the support layer maintains a combination of medium pore size and high porosity, providing the required load-bearing capacity without sacrificing permeability. The overall compressive strength and elastic modulus of the material are best in Example 2 (87MPa, 179MPa) among the three groups, followed by Examples 1 and 3 (59-74MPa, 135-152MPa). This verifies that the synergistic design of "double support layer + biodegradable isolation layer + gradient pore size" can take into account both mechanical support and the temporal induction of central zone bone fusion in cranioplasty, achieving the goal of early stability, later connectivity and integration.

[0100] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0101] While the present invention has been disclosed above, it is not limited thereto. Any person skilled in the art can make various modifications and alterations without departing from the spirit and scope of the invention; therefore, the scope of protection of the present invention should be determined by the scope defined in the claims.

Claims

1. A cranial repair body, characterized in that, The application relates to a skull repair body, which comprises: a first induction layer, a first support layer, a separation layer, a second support layer and a second induction layer arranged in sequence from the inner side to the outer side; the first induction layer and the second induction layer are formed by materials containing at least mineralized collagen; the first support layer and the second support layer are formed by high polymer materials and nano-bioceramic particles; the separation layer is formed by degradable polymer materials; the separation layer is adapted to realize physical separation between the first support layer and the second support layer before the degradable polymer materials are degraded, and to form three-dimensional communication channels after the degradable polymer materials are completely degraded; the average pore diameter of the three-dimensional communication channels is smaller than the average pore diameters of the first induction layer, the first support layer, the second support layer and the second induction layer respectively. The pore diameters of the first induction layer and the first support layer are distributed in a gradient decreasing manner from the inner side to the separation layer; the pore diameters of the second induction layer and the second support layer are distributed in a gradient decreasing manner from the outer side to the separation layer; the average pore diameter of the first support layer is smaller than the average pore diameter of the first induction layer; the average pore diameter of the second support layer is smaller than the average pore diameter of the second induction layer.

2. The cranial repair of claim 1, wherein The materials forming the first induction layer and the second induction layer further contain at least one of hydroxyapatite and collagen.

3. The cranial repair of claim 1, wherein The materials forming the first induction layer and the second induction layer further contain at least one of growth factors and metal ions.

4. The cranial repair of claim 1 or 3, wherein, The nano-bioceramic particles contain at least one of nano-hydroxyapatite, beta-tricalcium phosphate and silicate bioactive ceramic; the degradable polymer materials are polycaprolactone, polylactic acid-glycolic acid copolymer or polytrimethylene carbonate; the high polymer materials contain at least one of polylactic acid and polyethylene glycol.

5. The cranial repair of claim 1, wherein The average pore diameter of the three-dimensional communication channels is 20-90 mu m, and the average pore diameters of the first induction layer and the second induction layer are 200-400 mu m.

6. The cranial repair of claim 1, wherein The thickness of the separation layer is 0.2-0.5 mm; the thicknesses of the first induction layer and the second induction layer are 0.5-1.0 mm; and the thicknesses of the first support layer and the second support layer are 2-3 mm.

7. The cranial repair of claim 1, wherein The application further relates to a preparation method of the skull repair body, which comprises the following steps:

8. A method of manufacturing a cranial repair according to any one of claims 1 to 7, characterized in that, forming a three-dimensional model of a skull repair body according to scanning data of a skull defect part of a patient and introducing the three-dimensional model into a fused deposition modeling 3D printing device; printing a first induction layer on a specific mold by the fused deposition modeling 3D printing device based on a first printing material containing at least mineralized collagen; forming a first support layer covering the first induction layer by the fused deposition modeling 3D printing device based on a second printing material formed by dispersing nano-bioceramic particles in a high polymer material solution; forming a separation layer covering the first support layer by the fused deposition modeling 3D printing device based on a third printing material formed by degradable polymer materials; forming a second support layer covering the separation layer by the fused deposition modeling 3D printing device based on the second printing material; and ​ Forming a second inducing layer covering the second support layer by a fused deposition modeling 3D printing device with the first printing material, forming the skull prosthesis.

9. A method of manufacturing a cranial repair according to any one of claims 1 to 7, characterized in that, The method comprises the steps of: According to the scanning data of the skull defect site of the patient, a corresponding three-dimensional model of the skull prosthesis is formed and introduced into a stereolithography 3D printing device; Mixing a high molecular material, nano-bioceramic particles and a photoinitiator to form a photosensitive resin material; Forming the first support layer and the second support layer by the stereolithography 3D printing device with the photosensitive resin material; Spraying a solution containing a degradable polymer material between the first support layer and the second support layer to form the isolation layer; Based on the prepared inducing layer slurry including at least mineralized collagen, forming a first inducing layer on the inner side of the first support layer and a second inducing layer on the outer side of the second support layer by the stereolithography 3D printing device, forming the skull prosthesis.

10. A method of manufacturing a cranial repair according to any one of claims 1 to 7, characterised in that, The method comprises the steps of: According to the scanning data of the skull defect site of the patient, a corresponding three-dimensional model of the skull prosthesis is formed; Mixing a high molecular material, nano-bioceramic particles and a plasticizer to form a support layer plate by an injection molding machine; Heating the degradable polymer material to a molten state to form a film; Preparing an inducing layer gel including at least mineralized collagen; According to the three-dimensional model of the skull prosthesis, using a numerical control machining device to cut and carve the support layer plate to form the first support layer and the second support layer; Placing the film between the first support layer and the second support layer and tightly combining it with the first support layer and the second support layer by a hot pressing process; Injecting the inducing layer gel into the inner side of the first support layer to form a first inducing layer and into the outer side of the second support layer to form a second inducing layer; Placing the assembly including the first inducing layer, the first support layer, the isolation layer, the second support layer and the second inducing layer in a vacuum drying box for drying treatment, forming the skull prosthesis.

Images