A Micro-Patterned, hiPSC-Derived Vascular Graft with Enhanced Endothelialization via Shear Redistribution

Abstract

Small-diameter vascular grafts that can grow with pediatric patients and resist thrombosis remain an unmet need, primarily due to slow and unstable endothelialization. Here, we engineer a tri-layer, human induced pluripotent stem cell (hiPSC)-derived vascular graft featuring a soft, patterned lumen. We introduce a scalable soft-lithography method to imprint longitudinal micro-grooves directly into the lumen of compliant hydrogel tubes, a key advance for cell-laden constructs. Computational fluid dynamics reveals that these grooves redistribute wall shear stress into protective low-shear valleys and aligning high-shear ridges without increasing the mean load. This engineered shear landscape, combined with a bioactive elastin-like recombinamer (ELR) hydrogel matrix, synergistically enhances hiPSC-endothelial cell (hiPSC-EC) capture and retention under perfusion. Patterned grafts accelerate the formation of confluent, axially aligned endothelial monolayers with mature VE-cadherin junctions, outperforming non-patterned controls. Concurrently, smooth muscle cells within the graft wall deposit extracellular matrix, driving time-dependent mechanical maturation. This platform provides a physiologically relevant model for vascular disease and a promising strategy for engineering growth-competent pediatric grafts.