Liang Renjie, Li Rui, Mo Weidong, Zhang Xianzhu, Ye Jinchun, Xie Chang, Li Wenyue, Peng Zhi, Gu Yuqing, Huang Yuxuan, Zhang Shufang, Wang Xiaozhao, Ouyang Hongwei
Department of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Bioact Mater. 2024 Jul 4;40:541-556. doi: 10.1016/j.bioactmat.2024.06.024. eCollection 2024 Oct.
Although natural polymers have been widely used in constructing bone scaffolds, it still remains challenging to fabricate natural polymer-derived bone scaffolds with biomimetic mechanical properties as well as outstanding osteogenic properties for large-size and weight-bearing bone defects regeneration. Herein, an "organic-inorganic assembly" strategy is developed to construct silk fibroin (SF)-based bone scaffolds with the aforementioned merits. After secondary structure reshuffling, the 3.3-fold increment of β-sheet structures in SF hydrogel resulted in a 100-fold improvement of mineral-assembly efficacy via influencing the ion adsorption process and providing templates for mineral growth. Notably, abundant minerals were deposited within the hydrogel and also on the surface, which indicated entire mineral-assembly, which ensured the biomimetic mechanical properties of the digital light processing 3D printed SF hydrogel scaffolds with haversian-mimicking structure. experiments proved that the assembly between the mineral and SF results in rapid adhesion and enhanced osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. experiments further proved that the mineral-assembled SF hydrogel scaffold could significantly enhance integration and bone regeneration at the weight-bearing site within one month. This SF-based "organic-inorganic assembly" strategy sheds light on constructing cell-free, growth factor-free and natural polymer-derived bone scaffolds with biomimetic 3D structure, mechanical properties and excellent osteogenic properties.
尽管天然聚合物已被广泛用于构建骨支架，但制造具有仿生力学性能以及出色成骨性能的天然聚合物衍生骨支架以用于大尺寸和承重骨缺损再生仍然具有挑战性。在此，开发了一种“有机-无机组装”策略来构建具有上述优点的丝素蛋白（SF）基骨支架。经过二级结构重排后，SF水凝胶中β-折叠结构增加了3.3倍，通过影响离子吸附过程并为矿物质生长提供模板，使矿物质组装效率提高了100倍。值得注意的是，大量矿物质沉积在水凝胶内部以及表面，这表明实现了完全的矿物质组装，确保了具有哈弗斯管模拟结构的数字光处理3D打印SF水凝胶支架的仿生力学性能。实验证明，矿物质与SF之间的组装导致人骨髓间充质干细胞的快速黏附并增强其成骨分化。实验进一步证明，矿物质组装的SF水凝胶支架可在一个月内显著增强承重部位的整合和骨再生。这种基于SF的“有机-无机组装”策略为构建具有仿生3D结构、力学性能和出色成骨性能的无细胞、无生长因子且源自天然聚合物的骨支架提供了思路。
