Enhanced Osteogenesis of Bone Marrow‐Derived Mesenchymal Stem Cells by a Functionalized Silk Fibroin Hydrogel for Bone Defect Repair

Abstract Silk fibroin (SF) from Bombyx mori is a promising natural material for the synthesis of biocompatible and biodegradable hydrogels for use in biomedical applications from tissue engineering to drug delivery. However, weak gelation performance and the lack of biochemical cues to trigger cell proliferation and differentiation currently significantly limit its application in these areas. Herein, a biofunctional hydrogel containing SF (2.0%) and a small peptide gelator (e.g., NapFFRGD = 1.0 wt%) is generated via cooperative molecular self‐assembly. The introduction of NapFFRGD to SF is shown to significantly improve its gelation properties by lowering both its threshold gelation concentration to 2.0% and gelation time to 20 min under physiological conditions (pH = 7.4, 37 °C), as well as functionalizing the SF hydrogel with cell‐adhesive motifs (e.g., RGD). Besides mediating cell adhesion, the RGD ligands incorporated within the SF‐RGD gel promote the osteogenic differentiation of bone marrow‐derived mesenchymal stem cells encapsulated within the gel matrix, leading to bone regeneration in a mouse calvarial defect model, compared with a blank SF gel (2.0%, pH = 7.4). This work suggests that SF could be easily tailored with bioactive peptide gelators to afford bioactive hydrogels with favorable microenvironments for tissue regeneration applications.