介孔硅酸钙/类水滑石/胶原蛋白三维多孔支架的构建和骨修复性能研究

The ideal bone substitute not only needs to have excellent biocompatibility, bioactivity and mechanical properties, but also should possess good osteoinductivity and anti-infection property. Combining hydrothermal method, organic template method and freeze drying method, this project intends to design and fabricate mesoporous calcium silicate / hydrotalcite-like compound/ collagen 3D porous scaffold with core-shell structure. This hybrid scaffold has three-dimensional macroporous structure, mesoporous structure and plate-like structure of hydrotalcite-like compound. Interconnected macroporous structure facilitates the ingrowth of osteogenic cells and vascular cells. Mesoporous structure and plate-like structure in hydrotalcite-like compound can improve the drug delivery performance for antibiotics. By ion replacement, chemical ions with osteogenic effect can be stocked in the plate-like structure in hydrotalcite-like compound, which is expected to significantly enhance its bone repair performance. This project will study the fabrication mechanism of mesoporous calcium silicate / hydrotalcite-like/ collagen 3D porous scaffold, reveal the relationship between chemical composition, core-shell structure and bioactivity, biocompatibility, drug loading and release properties, study the effects of different chemical ions on osteoinduction of the hybrid scaffold, and investigate the effect and mechanism of the chemical ions with osteogenic effect on the adhesion, proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells. The implementation of this project has important theoretical significance and application value to the development of new bone substitutes.

理想的骨修复材料，不仅需要有优良的生物相容性、生物活性和力学性能，还需具备良好的骨诱导性和抗感染性能。本项目将结合水热法、有机模板法和冷冻干燥法，设计和构建具有核壳结构的介孔硅酸钙/类水滑石/胶原蛋白三维多孔支架。复合材料同时具有三维大孔结构、介孔结构和类水滑石的层状结构。相互贯通的大孔结构能够促进骨系细胞和血管长入；介孔硅酸钙和类水滑石的层状结构能够提高材料对抗生素的药物传递性能；通过离子替换的方式，将各种具有促成骨效应的化学离子引入类水滑石的层状结构内，能够显著增强材料的骨修复性能。本项目将研究材料的结构、形貌和形成机理，揭示材料的化学组成、核壳结构与生物活性、生物相容性和药物传递性能之间的关系，研究不同化学离子对于材料骨诱导性的影响，深入探讨各种化学离子对人骨髓间充质干细胞粘附、增殖和成骨分化的作用和分子机制。本项目的开展对于新型骨修复材料的开发具有重大的科学意义和实用价值。

在开放性外伤、慢性骨髓炎、恶性肿瘤根治术等造成的骨缺损修复手术中，如何有效的预防术后感染的发生一直是骨科临床的一大难题。为了解决这一难题，本课题通过水热法合成出具有典型层状结构的类水滑石纳米晶，通过离子替代的方式，合成具有不同化学元素组成的类水滑石纳米晶，并对制备的类水滑石纳米晶进行完整的材料学表征，阐明其形成机理。类水滑石纳米晶具有良好的生物活性和生物相容性。硅酸根型类水滑石纳米晶能够持续释放硅离子，硅离子能促进骨髓间充质干细胞的增殖和成骨分化，具有良好的体外、体内骨诱导性。类水滑石纳米晶对庆大霉素有良好的负载和缓释性能，负载了庆大霉素的类水滑石纳米晶具有良好的抗菌性能。另外，通过原位模板法制备出具有均一介孔结构的介孔硅酸钙，利用介孔硅酸钙包裹银纳米粒子的蛋-黄结构为模板，通过限域空间的伽尔瓦尼置换反应，得到介孔硅酸钙包裹金银合金核-壳纳米粒子。金银合金笼状结构的纳米粒子核能有效的吸收近红外光并转换成热能，介孔氧化硅外层能够更多的负载药物分子，实现光热与药物治疗的有机结合，在临床抗感染，抗肿瘤，抗骨质疏松治疗方面具有广阔的应用前景，是本课题的延续及拓展研究。