Abstract:
Timely vascularization and innervation of tissue in a patient are essential in successfully translating transplanted tissues into clinically relevant therapies. Here, suitable local microenvironments provided by collagen or gelatin-based hydrogels to support cell-based functional vascular-network formation have been investigated to shorten the time needed to vascularize engineered tissue. After mixing blood-vessel-forming cells into suitable hydrogels with controlled material properties, these embedded cells first form vascular lumens and quickly connect and anastomose with the patient’s vasculature. After connection occurs, blood flows to every corner inside the implanted hydrogel, and quickly forms perfused vascularized tissue at the subcutaneous site in mice within four days, which can shorten the time of angiogenesis and significantly improve the survival rate of the transplanted tissue. At the same time, host neurons migrated along growing blood vessels, and the density of neuron numbers was proportional to the blood vessels. How hydrogel properties mediated vascular network formation and further guided host neurons were investigated. Furthermore, this vascularized nerve tissue construct served as the implant to support the repair of abdominal and skeleton muscle defects, demonstrating that engineered vascular and neuronal networks benefit muscle tissue repair.