Vascularization strategies for human skin tissue engineering via 3D bioprinting

The skin is composed of many cells that are organized into different layers and connected by dense and complex vascular networks. This creates a dynamic microenvironment in which cells interact within the matrix. Significant advancements have been made in this field over the past decade, and various strategies have been developed for accelerating and enhancing skin regeneration. The primary challenge for successful skin grafts is the integration of the functional vasculature, which can supply essential nutrients and oxygen to cell-laden structures and damaged native tissues. An inadequate vascular network can lead to ischemia, which can cause slow wound healing—particularly in the case of chronic skin conditions. Therefore, blood vessel formation remains one of the most significant obstacles that skin tissue engineering must overcome to create vascularized skin tissue substitutes with specific living cells. Technological advances can augment effective vascularization. The three-dimensional (3D) bioprinting platform is a promising technology that allows precise deposition of living cells and bioactive materials. The application of this technology to skin tissue engineering can provide solutions for augmenting pre-vascularization in engineered in vitro skin models and in vivo skin substitutes. This review presents the significance of skin vascularization in in vitro modeling and in vivo wound healing. Various strategies and related applications involving 3D bioprinting technology are introduced for the biofabrication of enhanced vascularized skin in vitro and in vivo, followed by a discussion of their limitations and future research directions.