Artificial self-mineralized MSCs' niche mimics dynamic variations of ECM modulus during osteogenesis for rapid bone regeneration.

Abstract

The osteogenic differentiation of mesenchymal stem cells (MSCs) requires dynamic remodeling of the extracellular matrix (ECM) microenvironment. Biomimetic mineralization (BM) can recapitulate key features of the native bone microenvironment and thereby promote MSC osteogenesis. However, the development of artificial scaffolds capable of providing dynamically evolving mineralized niches for MSCs remains challenging, and the underlying osteogenic mechanisms are still poorly understood. In this study, a hierarchical graphene-doped polymethyl methacrylate (PMMA) scaffold was fabricated via vapor-induced phase separation. An organic-inorganic framework with continuous self-mineralization capability-composed of ovalbumin (OVA), tannins (TA), Ca²⁺, and PO₄^3--was engineered on the graphene surface through a simple two-step immersion process. This bone tissue mimetic architecture, combined with sustained in situ mineralization, establishes an optimal dynamic niche that supports MSC adhesion and drives robust osteogenic differentiation. Furthermore, the self-mineralized calcium nodules synergize with MSC-mediated calcium deposition during osteogenesis, leading to accelerated scaffold remodeling and a significantly shortened bone repair timeline. Collectively, the hierarchical scaffold featuring a self-mineralizing MSC niche exhibits strong potential for the regeneration of critical-sized bone defects.