基于金属-有机框架（MOFs）的活性离子缓释型多孔复合支架构建及其促骨再生功能的研究

Bone tissue engineering involves the use of a cell-seeded scaffold with specific biochemical and biophysical functions. Finding a proper artificially-created scaffold is vital for achieving engineered tissues. One promising approach is to design scaffolds containing the inorganic elements such as Zn2+ that have osteoinductive activity. In order to improve the controllable release of the bone-induced metal ions from the scaffold, we will propose the strategy that using metal-organic frameworks (MOFs) nanoparticles for controlled release of bone-induced metal ions to mediate the osteogenic differentiation of MSCs. We will apply the biopanning technique to map out the sequences that can affinity specifically to silk fibroin (SF) and MOFs, respectively, and design the peptide by combining these two amino acid sequences. This peptide will drive the MOFs nanoparticles to be distributed evenly in the SF solution. Using the gradient freeze-drying technology, we will obtain the MOFs/SF solid scaffolds containing an even distribution of MOFs nanoparticles. Therefore, controllable release of bone-induced metal ions will be achieved in our strategy. Furthermore, the obtained MOFs/SF scaffolds will have a laminar porosity that helps to improve the mechanical properties of scaffolds. We will test the bone regeneration In Vitro and In Vivo.. This project is interdisciplinary research intersected by materials, medicine and biology. It will provide important insights into the relationship between controllable release of bone-induced metal ions from scaffolds and the osteoblastic differentiation of BMSCs. It will lay foundation for the rational design of the MOFs nanoparticles based scaffolds that direct cell behaviors to benefit functional bone tissue engineering and regenerative medicine.

骨组织工程支架材料掺杂骨诱导金属离子是解决骨缺损修复的有效途径之一，但还需解决金属离子释放不稳定等问题。本项目拟用金属-有机框架（Meta-Organic Frameworks，MOFs）为骨诱导金属离子源，以丝素蛋白为基底材料，利用生物淘选技术，筛选并设计与MOFs和丝素蛋白具有亲和性的多肽，促使MOFs分布均匀于丝素蛋白溶液，通过梯度冷冻干燥技术获得具有力学性能优良、有序片层多孔结构、可控缓释骨诱导金属离子的骨修复材料。并通过干细胞培养与动物体内植入验证其骨再生功能。. 本项目首次提出了利用MOFs、生物淘选技术与梯度冷冻干燥法相结合，构建基于活性离子缓释型多孔复合骨修复材料的思路，充分体现了材料学、医学与生物学等学科的交叉性，为临床骨缺损修复提供新的设计方案和实验支撑，也为骨修复材料的制备提供一定的理论指导。

骨组织工程支架材料掺杂骨诱导金属离子是解决骨缺损修复的有效途径之一；然而，传统的复合支架不具备可控、稳定的金属离子释放能力。针对这一问题，本项目以金属-有机框架为骨诱导金属离子源，以丝素蛋白为基底材料，利用生物淘选技术，筛选并设计与金属-有机框架和丝素蛋白具有亲和性的多肽，促使金属-有机框架均匀分布于丝素蛋白溶液，通过梯度冷冻干燥技术获得具有优良的力学性能、有序片层多孔结构、可控缓释骨诱导金属离子的骨修复复合支架。通过细胞、动物实验评价了材料的促成骨性能，研究了其对细胞分化途径的调控和基因表达等的影响等。所形成的主要科学研究结论包括：（1）发现亲和肽与ZIF-8和SF具有特异性的结合能力，通过双功能肽的辅助制备了ZIF-8分布均匀的ZIF-8/SF复合支架；（2）证明ZIF-8/SF-亲和肽复合支架的力学性能，并且可以实现锌离子的长期均匀缓释；（3）通过细胞实验证实ZIF-8/SF-亲和肽复合支架具有良好的生物相容性；（4）基于细胞分化实验和动物模型，进一步阐明SF-多肽复合材料的骨修复功能。通过本项目的研究，获取了定制的亲和肽，并探明了材料的组成、微结构以及骨诱导金属离子释放规律对骨组织再生的影响，有望深化和提升生物材料与细胞相互作用的认识和设计，在骨组织修复方面具有较高的应用价值。基于项目研究成果，研究团队在Advanced Materials、ACS Applied Materials & Interfaces、Advanced Healthcare Materials等高水平国际学术期刊多次发表学术论文，获得国内外学术同行的广泛认可；申请中国发明专利13项；本项目的完成显著提升了本研究团队的科研水平和学术素质，为培养了青年科研人才做出了重要贡献。