Exploring the angiogenic potential of skin patches with endothelial cell patterns fabricated via in-bath 3D bioprinting using light-activated bioink for enhanced wound healing

The lack of functional vasculature in skin substitutes leads to ischemia and delayed regeneration, highlighting the need for effective prevascularization strategies. This study employs in-bath 3D bioprinting to fabricate prevascularized skin patches by patterning endothelial cells (ECs) within light-activated decellularized extracellular matrix (dECM) bioink. ECs were printed in line, grid, and dot patterns, rapidly crosslinked under visible light to achieve high shape fidelity, even with low dECM concentrations. Integration of human adipose-derived stem cells further enhanced vascular sprouting. Among the patterns, the grid configuration demonstrated the highest microvessel formation and significantly improved neovascularization and wound healing in a murine model. A mechanistic analysis suggests that differences in surface area, linked to integrin-mediated and vascular endothelial growth factor-related pathways, drive the superior outcomes of the grid pattern. This study underscores the potential of tailored vascular patterning in advancing bioprinted skin patches as innovative solutions for skin regeneration.