Blood Vessels Bioengineered from Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells and Functional Scaffolds

Abstract

The development of small-diameter vascular grafts remains a major challenge in tissue engineering due to limited remodelling and regenerative capabilities. While strides have been made on the biofabrication of vessel mimics, little clinical translation success had been achieved to treat coronary artery disease (CAD). This study aimed to fabricate patient-specific bioengineered vessels using induced pluripotent stem cells (iPSCs) and functionalised biodegradable scaffolds. Human iPSCs were differentiated into mesenchymal stem cells (iMSCs) using SB431542, then further into vascular smooth muscle cells (VSMCs) with PDGF-BB and TGF-{beta}1. Human bone marrow-derived MSCs (hBM-MSCs) were used to optimize differentiation protocols. Electrospun poly-L-lactide (PLLA) scaffolds coated with silk fibroin improved cell adhesion and proliferation. Both hBM-MSCs and iMSCs were seeded on these scaffolds for in-scaffold VSMC differentiation. The resulting cell-laden scaffolds were rolled into tubular structures ([~]3 mm inner diameter, [~]20 mm length). Over 34-36 days, iPSCs differentiated into iMSCs expressing MSC markers (CD73, CD90, CD105), followed by successful VSMC differentiation within 9 days, confirmed by -SMA, CNN1, SM22, and MYH-11 expression. Silk fibroin-coated PLLA scaffolds enhanced MSC adhesion and proliferation compared to uncoated scaffolds. The engineered tubular grafts displayed VSMC markers and mechanical properties akin to autologous coronary artery bypass grafting (CABG) grafts. This study developed a versatile method to fabricate tissue-engineered blood vessels using stem cells and silk fibroin-coated scaffolds. The resulting grafts exhibited tunica media-like structures and mechanical properties comparable to autografts used in CABG, showing strong potential for clinical application.