Engineering a Chemically Defined Hydrogel Bioink for Direct Bioprinting of Microvasculature

• Published in: Biomacromolecules Vol. 22; no. 2; pp. 275 - 288
• Main Authors: Barrs, Ryan W, Jia, Jia, Ward, Michael, Richards, Dylan J, Yao, Hai, Yost, Michael J, Mei, Ying
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 08.02.2021
• Subjects: alginates; biodegradability; Bioprinting; collagen; crosslinking; fibronectins; Hydrogels; Microvessels; morphogenesis; peptides; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds; Vascular Endothelial Growth Factor A; viscoelasticity
• ISSN: 1525-7797; 1526-4602; 1526-4602
• DOI: 10.1021/acs.biomac.0c00947

Vascularizing printed tissues is a critical challenge in bioprinting. While protein-based hydrogel bioinks have been successfully used to bioprint microvasculature, their compositions are ill-defined and subject to batch variation. Few studies have focused on engineering proangiogenic bioinks with defined properties to direct endogenous microvascular network formation after printing. Here, a peptide-functionalized alginate hydrogel bioink with defined mechanical, rheological, and biochemical properties is developed for direct bioprinting of microvascularized tissues. An integrin-binding peptide (RGD) and a vascular endothelial growth factor-mimetic peptide with a protease-sensitive linker are conjugated onto a biodegradable alginate to synergistically promote vascular morphogenesis and capillary-scale endothelial tube formation. Partial ionic crosslinking before printing converts the otherwise unprintable hydrogel into a viscoelastic bioink with excellent printability and cytocompatibility. We use the bioink to fabricate a compartmentalized vascularized tissue construct, wherein we observe pericyte-endothelial cell colocalization and angiogenic sprouting across a tissue interface, accompanied by deposition of fibronectin and collagen in vascular and tissue components, respectively. This study provides a tunable and translational “off-the-shelf” hydrogel bioink with defined composition for vascularized bioprinting.