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

In vivo injectable extracellular matrix (ECM) derived hydrogel that is suitable for cell encapsulation has always been the holy grail in tissue engineering. Nevertheless, these hydrogels still fall short today of meeting three crucial criteria: flexibility on the injectability time-window, autonomous self-healing of the injected hydrogel, and shape-retention under aqueous conditions. Here we report the development of a collagen-based injectable hydrogel, crosslinked by cycloaddition reaction between furan and maleimide groups, that is injectable up to 48 hours after preparation and can undergo complete autonomous self-healing after injection. Furthermore, this hydrogel can retain its shape and size over several years when stored in buffer, yet can be degraded within hours when treated with collagenase. The biocompatibility of this hydrogel was demonstrated in vitro by cell-culture and in vivo by subcutaneous implantation in rats.