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

Abstract

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.

Endothelialized microvessels fabricated by microfluidics facilitate osteogenic differentiation and promote bone repair

“…The ability to process and assemble BMVs into 3D vascular network is also an important consideration for better application in tissue engineering [70]. In order to meet the needs of different environments in the body, BMVs are needed to assemble into different structures [71,72].…”

Three dimensional (bio)printing of blood vessels: from vascularized tissues to functional arteries

“…When choosing a (bio)printing technique, we may have a general idea of the possible outcomes of the designed constructs guided by their technical limitations. However, as presented, other factors like the addition of growth factors, the choice of cell sources, mechanical stimulation, and surface topography may help to recreate an adequate physiological environment and further enhance vascularization in the (bio)printed constructs [96,160,161,163,195,196].…”

Strategies for vascularized skin modelsin vitro

“…However, few methods could control the formation of vascular branches in a self-assembly way. Zhang et al 30 established a cell-laden construct as a vascular model via three-dimensional bioprinting to confirm that a mechanical force (cell-mediated tension) could control the growth of blood vessels. After 14 days of culture, the growth direction of the blood vessels was exhibited in the (Fig.…”