Dynamic control of integrin signaling for cell manipulation via molecularly imprinted decoy receptor

Integrin plays a crucial role in human immune system activation and stem cell differentiation through interactions with the extracellular matrix (ECM). Reversible modulation of integrin signaling has illuminated the road toward broad-spectrum disease treatment and tissue regeneration. In this regard, an integrin-like decoy receptor, termed molecularly imprinted polymer (MIP), was synthesized via solid-phase imprinting to target the Arg-Gly-Asp (RGD) sequence, an integrin-binding motif abundantly present in the ECM. The MIP, with temperature-dependent RGD affinity, enabled dynamic intervention in integrin signaling, thereby modulating integrin-RGD-mediated immune response and cell differentiation. The MIP could, on demand, orchestrate macrophage phenotypes to display proinflammatory or anti-inflammatory traits, potentially beneficial at the early stage of tissue injury. Furthermore, stem cell fates could be controlled by MIP, showing potential to prevent hyperplasia caused by excessive differentiation. The proof-of-concept studies demonstrate the feasibility of MIP-based decoy receptors in the dynamic control of integrin signals and cell evolution, showing promise in tissue repair and related diseases.