增材制造梯度孔透辉石基生物活性陶瓷棒材及孔道功能增强治疗股骨头坏死研究

Osteonecrosis of the femoral head (ONFH) is a degenerative disease that seriously threatens human health. Without prompt treatment and ideal implants used for hip preservation, the femoral head tends to deteriorate and collapse, which eventually lead to total hip arthroplasty. The objective of this proposal is to design and fabricate the new multifunctional diopside (CaMgSi2O6) bioceramic-based rods with interconnective gradient pore distribution along the axis, to resolve the problems with respective to infection/inflammation control, long-term biomechanical maintenance, preservation of blood supply, control of the disease progression and other related clinical treatments. First, a three-dimensional printing technology was employed to construct the biopside bioceramic bars with interconnective pore distribution via magnesium-doped wollastonite-assisted sintering. Furthermore，this proposal systematically analyzes the effect of the amorphous mesoporous SrO/SeO-doping diopside precursor coating in the pore-wall on the long-term mechanical properties and stability, and then explore the modified layer and the ion dissolution products to regulate immune cells, vascular cells and osteogenic stem cells. To employ the pathological animal model of avascular necrosis of the femoral head, we will evaluate the efficiency and best effect of gradient pore microstructure and ion releasing combinants on mediating angiogenesis and new bone regeneration in bioceramic rods. The aim of this proposal is to demonstrate the long-term maintenance of blood supply in necrotic areas and the biomechanical evolution of porous bioceramic rods and the reliability of durable mechanical support. Meanwhile, it is helpful to develop the tissue-engineering combination therapy for ONFH and ONFH-derived bone injury, and thus to provide knowledge of regenerative medicine on the basis of the new multifunctional and high biologically active calcium-magnesium silicate porous biomaterials.

股骨头坏死是严重威胁民众健康的重大疾病，因施治不及时、植入材料性能不足等问题，使得病程控制难度大，甚至致残或不得不进行关节置换。本项目拟设计一种轴向梯度孔分布的功能改性透辉石基生物陶瓷棒材，以此解决感染或炎症控制、生物力学长期维持和长久血供维持，以期解决严控病程发展的临床治疗瓶颈问题。首先运用光固化三维打印技术构建镁掺杂硅灰石助烧结增强透辉石陶瓷梯度孔棒材，系统分析锶、硒功能离子掺杂非晶介孔透辉石梯度孔改性层对棒材力学性能长期稳定性的影响规律，全面探讨修饰改性层降解及活性离子溶出剂量调控免疫细胞、成血管/成骨相关干细胞的活性水平及最佳效应；运用股骨头缺血坏死病理模型，深入研究陶瓷棒材轴向梯度孔微结构及释放离子组合物介导新生血管化再生和炎症控制的效率及效果，充分论证坏死区血供长期维持、多孔棒材生物力学演化规律及持久支撑的可靠性，为发展新型多功能高生物学效应钙镁硅酸盐陶瓷棒材奠定技术与理论基础

股骨头坏死是一种严重威胁民众健康的骨科常见疾病，可能导致髋关节的功能障碍甚至残疾，带来沉重的社会和经济负担。目前临床上缺乏逆转晚期股骨头坏死的可靠办法，而常规的早中期保髋手术因缺乏合适的功能性内植入材料导致成功率仍有待提高。本项目利用3D打印技术制备钙镁硅酸盐基多孔生物陶瓷棒材，通过孔型结构优化设计及孔道壁表面修饰改性，以期达到促进早期快速血运重建、持续促新骨再生和稳定力学支撑的效果，为通过骨组织工程技术治疗股骨头坏死的临床转化研究提供技术与理论支持。. 首先利用光固化3D打印技术构建镁掺杂钙-硅基多孔陶瓷支架，以CSi-Mgx作为涂层材料，运用表面功能化技术使支架孔道壁表面和CSi-Mgx涂层通过静电作用相互吸附。研究结果表明CSi- Mgx涂层赋予支架在具备互连贯通孔道的同时具有良好的力学强度、生物相容性及成骨性能，为临床治疗大面积骨缺损提供了一种新型方法；其次利用数字光处理3D打印技术（DLP）制备集成不同孔型、孔径的多孔生物陶瓷棒型支架（CSi-Mg8），并深入探究微观孔道结构特征对其机械力学性能、离子缓释能力和体内早期血管化效率的影响。结果表明仿松质骨螺旋体型孔（gyroid）的几何形状虽然抗压能力有限，但其连续孔壁曲率特征对多孔生物陶瓷支架的生物降解、血管细胞迁移和血管长入具有重要意义；最后利用孔道优化设计和表面修饰改性技术制备了高强度高活性掺镁硅灰石梯度孔陶瓷棒材，兔股骨头坏死动物模型初步研究结果表明其具有高力学可靠性及高生物活性，为股骨头坏死的组织工程修复提供了理论依据。. 本项目通过医工深度合作的多学科协作研究，探索股骨头坏死区血供长期维持、多孔棒材生物力学演化规律及持久支撑的可靠性，为发展新型多功能高生物学效应钙镁硅酸盐陶瓷棒材奠定技术与理论基础。以本项目研究成果为基础，发表学术论文10篇，其中SCI收录9篇，培养研究生9人。