Advanced Strategies in Bone Tissue Engineering: “Membrane-Jelly” Hydrogel System to Improve Bone Marrow Stem Cell Osteogenic Differentiation and Bone Regeneration

Traditional bone tissue engineering presents several challenges, including difficulties in obtaining seed cells, relatively slow proliferation within scaffolds, and the potential to induce postimplantation immunogenic reactions. A promising direction for bone-tissue regeneration involves the development of cell-free scaffolds with superior physicochemical and biological properties. This study focused on encapsulating bone marrow stem cells (BMSCs) within stromal cell-derived factor-1α (SDF-1α)-loaded silk fibroin-gelatin methacryloyl (SF-GelMA) hydrogel to create a ″membrane-jelly″ culture platform. Within a specific concentration range, SDF-1α positively influenced BMSC induction and promoted osteogenic differentiation. Decellularized extracellular matrix mimics the stem cell microenvironment, enhancing BMSC adhesion and proliferation, while preventing the loss of stemness. Building upon this foundation, the SDF-1α/GelMA-SF hydrogel matrix provides mechanical support for both the recruitment of BMSCs and their subsequent osteogenic differentiation. Furthermore, it activates various signaling pathways, including bile acid, Notch pathway, and G protein-coupled receptor signaling according to the GO and KEGG results of the RNAseq, thereby synergistically promoting elevated expression of osteogenic markers in BMSCs from multiple perspectives. This comprehensive approach harnesses osteoinductive capacity and accelerates bone tissue regeneration. This system is expected to represent an advanced strategy for bone tissue engineering.