Interfacial Silicification Efficiently Drives Osteogenic Differentiation of Mesenchymal Stem Cells without Any Exogenous Osteoinductive Factor

Mesenchymal stem cells (MSCs) are pluripotent adult stem cells capable of differentiating into various cell types, including osteoblasts. Efficiently directing MSC differentiation is crucial for regenerative medicine, but current strategies often rely on complex, media-dependent systems. Here, we introduce an innovative technology─interfacial silicification, which efficiently induces MSC osteogenic differentiation without the need for exogenous osteoinductive factors such as bone morphogenetic proteins-2 (BMP-2) and dexamethasone. This approach utilizes an amphiphilic peptide to facilitate the accumulation and condensation of silica precursors at the cell interface. The hydrophobic segment of the peptide anchors it to the cell membrane, while the hydrophilic RRIL sequence drives controlled silica deposition. Omic analyses revealed that interfacial silicification significantly alters the MSC extracellular matrix, enhances the production of bone matrix proteins such as osteocalcin and collagen type I, and upregulates key osteogenic factors, including BMPs and RUNX2, thereby inducing robust osteogenic differentiation in both mouse and human MSCs. Notably, silicified MSCs exhibited increased alkaline phosphatase activity, enhanced expression of bone matrix proteins, and improved mineralization. Together, this simple, media-independent method opens a new avenue for directing MSCs differentiation in regenerative medicine.