Mechanoadaptive polysaccharide conjugates architect pro-healing microenvironments via dynamic stress redistribution in skin defects

The tip stress concentration in linear wounds, a clinically prevalent issue yet overshadowed by circular defect studies, and chronic biotemporal discordance (static biomaterials versus dynamic tissue remodeling) remain largely underexplored, severely impeding wound healing. Here, an adhesive bioconjugate platform, HADEX, composed of two types of micrometer-sized polysaccharide-derived granules, was constructed for precise shaping and manipulation. Combining finite element modeling with a dynamically cross-linking adhesive driven by fluid convection, HADEX achieved both conformal tissue adhesion and modulation of the stress distribution within wet, linear wounds, thereby restoring tissue pretension. Furthermore, HADEX facilitated a seamless load transfer to regenerating tissue through synchronized HADEX degradation and endogenous extracellular matrix deposition. To validate the efficacy of HADEX, we demonstrated successful sutureless in vivo closure and healing of linear wounds in both the normal/diabetic rat and porcine skin incision models. The integration of computational design with biomaterials established a foundation for personalized, mechanics-informed regenerative therapies.