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.