Injectable pH-responsive adhesive hydrogels for bone tissue engineering inspired by the underwater attachment strategy of marine mussels

A major challenge in tissue engineering is the development of alternatives to traditional bone autografts and allografts that can regenerate critical-sized bone defects. Here we present the design of injectable pH-responsive doublecrosslinked adhesive hydrogels inspired by the molecular mechanism and environmental post-processing of marine mussel adhesive. Nine adhesive hydrogel formulations were developed through the conjugation of crosslinkable catechol functional groups (DOPA) and the synthetic oligomer oligo[poly(ethylene glycol) fumarate] (OPF), varying the DOPA content (w/w%) and molecular weight (MW) of the OPF backbone to produce formulations with a range of swelling ratios, porosities, and crosslink densities. DOPA incorporation altered the surface chemistry, mechanical properties, and surface topography of hydrogels, resulting in an increase in material stiffness, slower degradation, and enhanced pre-osteoblast cell attachment and proliferation. When injected within simulated bone defects, DOPA-mediated interfacial adhesive interactions also prevented the displacement of scaffolds, an effect that was maintained even after swelling within physiological conditions. Taken together, OPF-DOPA hydrogels represent a promising new material to enhanced tissue integration and the prevention of the post-implantation migration of scaffolds that can occur due to biomechanical loading in vivo.