Widespread clinical use of vascularized composite allotransplantation (VCA) is hindered by the side effects of systemic immunosuppressive drugs, such as tacrolimus. Gajanayake et al. loaded tacrolimus into an injectable self-assembled hydrogel, which releases the drug in response to proteolytic enzymes that are overexpressed during inflammation. A single injection of the hydrogel into a rat hindlimb transplantation model significantly prolonged graft survival and reduced the immune response, compared to tacrolimus only-treated recipients.