Mechano-regulation of vascular network formation without branches in 3D bioprinted cell-laden hydrogel constructs

Restoration of a wound is a common surgical procedure in clinic. Currently, the skin required for clinical use is taken from the patient's own body. However, it can be difficult to obtain enough skin sources for large-sized wounds and thus surgeons have started using commercial skin substitutes. The current commercial skin, which includes epidermis substitute, dermis substitute, and bilateral skin substitute, has been popularized in clinic. However, the application is limited by the occurrence of ischemia necrosis after transplantation. Recent studies suggest the use of pre-vascularized skin substitutes for wound healing is a promising area in the research field of skin tissue engineering. Pre-vascularization can be induced by changes in cultivation periods, exertion of mechanical stimuli, or coculture with endothelial cells and various factors. However, few methods could control the formation of vascular branches in engineering tissue in a self-assembly way. In this study, we use three-dimensional (3D) printing technology to confirm that a mechanical force can control the growth of blood vessels in the direction of mechanical stimulation with no branches, and that Yes-associated protein activity is involved in the regulatory progress. In vivo experiments verified that the blood vessels successfully function for blood circulation, and maintain the same direction. Results provide a theoretical basis for products of pre-vascularized skin tissues and other organs created by 3D bioprinting.