Wenbo He, Dongdong Ling, Yue Ma, Yansi Zhou, Wei Qi, Guoqing Pan
Dynamic biointerfaces, as materials that mimic extracellular matrix properties, confer surfaces the ability to dynamically recognize cell membrane receptors through the reversible presentation of active ligands, thereby modulating cell adhesion, migration, proliferation, and differentiation. However, chemical strategies used in the design of dynamic biointerfaces have limitations, including excessive introduction of exogenous chemical components and potential biosafety concerns. This study leveraged the specific recognition of mannose by concanavalin A (ConA) and glucose-mediated competitive displacement to reversibly present bioactive ligands comprising mannose-conjugated cell-adhesive peptide RGD and osteogenic growth peptide (OGP), designated MR and MO, respectively, thereby constructing a dynamic biointerface for spatiotemporal regulation of cell fate. The results demonstrated that MR ligand presentation promotes adhesion of L929 and EC cells, with glucose-mediated adhesion-desorption transitions. Additionally, it directionally modulates RAW 264.7 toward M2 polarization while inhibiting M1 polarization. This polarization effect exhibits time dependency and can be reversed by glucose. Moreover, the interface enables sequential ligand switching through a concentration-dependent MR/MO ligand competition mechanism: MR ligands promote early BMSCs' adhesion, while MO ligands induce later osteogenic differentiation. This entire process is reversibly modulated by glucose, thereby achieving precise regulation of cellular behavior. This work presents a feasible strategy for designing intelligent biomaterials that are responsive to endogenous metabolic signals, with promising utility in precision regenerative medicine and therapeutic interventions for metabolic disorders.