Engineering biomimetic silk fibroin hydrogel scaffolds with“organic-inorganic assembly”strategy for rapid bone regeneration

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 ofβ-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.In vitro 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.In vivo 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.