3D printable dynamic hydrogel via entangled biomolecular coacervate towards an ECM-like scaffold

The extracellular matrix (ECM) is a dynamic, hierarchically structured network essential for mechanical support and regulation of cell behavior. Mimicking its complexity in synthetic materials remains a major challenge. Here, we present a straightforward strategy to fabricate ECM-inspired, dynamically phase-separated hydrogels (DyPS-MAPgel) by methacrylation of mussel adhesive proteins (MAPs), followed by metal ion-induced phase separation and in situ photopolymerization. Leveraging the intrinsic ability of MAPs to undergo biomolecular phase separation and subsequent covalent crosslinking, the resulting hydrogels exhibit tunable mechanical properties, strong tissue adhesion, self-healing, antibacterial, and antioxidant activities. Importantly, DyPS-MAPgels support stem cell proliferation and lineage-specific differentiation both in vitro and in vivo through integrin-dependent mechanotransduction pathways. This work demonstrates the potential of phase separation-mediated assembly as a robust strategy for constructing ECM-mimetic materials and provides insights into ECM-cell interactions. Our findings offer a versatile platform for regenerative medicine applications, including bioadhesion, 3D bioprinting, and tissue engineering.