Tannic acid–metal single-cell nano-coatings regulate bone mesenchymal stem cell fate through ion-specific pericellular microenvironments

Abstract

Bone and cartilage regeneration remains a major clinical challenge due to the limited intrinsic repair capacity of musculoskeletal tissues. Biomaterial strategies capable of regulating stem cell behavior at the single-cell level offer new opportunities for precise control of tissue regeneration. Herein, we developed tannic acid–metal (TA–metal) coordination systems incorporating Fe³⁺, Sr²⁺, and Mg²⁺ ions as single-cell nano-coatings to modulate the pericellular microenvironment of bone marrow–derived mesenchymal stem cells (BMSCs). The physicochemical properties of the TA–metal coatings, including protein adsorption, surface morphology, surface charge, ion release behavior, and elemental composition, were systematically characterized. All TA–metal systems formed conformal coatings on individual cells with excellent cytocompatibility and showed detectable retention during early culture. The TA–metal nano-coatings significantly regulated cell morphology and cytoskeletal organization in a metal ion–dependent manner. Notably, TA–Sr and TA–Mg coatings promoted enhanced cell spreading and well-organized actin structures. Tri-lineage differentiation assays revealed distinct lineage-specific regulatory effects. TA–Fe nano-coatings preferentially enhanced adipogenic differentiation, whereas TA–Sr coatings significantly promoted chondrogenic matrix production while supporting osteogenic differentiation. TA–Mg nano-coatings exhibited the strongest osteogenic potential, as evidenced by increased alkaline phosphatase activity and extracellular matrix mineralization. Collectively, these results demonstrate that TA–metal single-cell nano-coatings enable programmable, ion-specific regulation of stem cell fate within an identical coordination framework. This cell-level biomaterial strategy provides a versatile platform for skeletal tissue engineering and cell-based regenerative therapies.