Shear-Induced Cycloreversion Leading to Shear-Thinning and Autonomous Self-Healing in an Injectable, Shape-Holding Collagen Hydrogel

In vivo injectable extracellular matrix (ECM) derived hydrogels that are suitable for cell encapsulation have always been the holy grail in tissue engineering. Nevertheless, these hydrogels still fall short today of meeting three crucial criteria: (a) flexibility on the injectability time window, (b) autonomous self-healing of the injected hydrogel, and (c) shape-retention under aqueous conditions. Here we report the development of a collagen-based injectable hydrogel, cross-linked by cycloaddition reaction between furan and maleimide groups, that (a) is injectable up to 48 h after preparation, (b) can undergo complete autonomous self-healing after injection, (c) can retain its shape and size over several years when stored in the buffer, (d) can be degraded within hours when treated with collagenase, (e) is biocompatible as demonstrated by in vitro cell-culture, and (f) is completely resorbable in vivo when implanted subcutaneously in rats without causing any inflammation.