Advanced PEG-tyramine biomaterial ink for precision engineering of perfusable and flexible small-diameter vascular constructs via coaxial printing.

Abstract

Vascularization is crucial for providing nutrients and oxygen to cells while removing waste. Despite advances in 3D-bioprinting, the fabrication of structures with void spaces and channels remains challenging. This study presents a novel approach to create robust yet flexible and permeable small (600-1300 μm) artificial vessels in a single processing step using 3D coaxial extrusion printing of a biomaterial ink, based on tyramine-modified polyethylene glycol (PEG-Tyr). We combined the gelatin biocompatibility/activity, robustness of PEG-Tyr and alginate with the shear-thinning properties of methylcellulose (MC) in a new biomaterial ink for the fabrication of bioinspired vessels. Chemical characterization using NMR and FTIR spectroscopy confirmed the successful modification of PEG with Tyr and rheological characterization indicated that the addition of PEG-Tyr decreased the viscosity of the ink. Enzyme-mediated crosslinking of PEG-Tyr allowed the formation of covalent crosslinks within the hydrogel chains, ensuring its stability. PEG-Tyr units improved the mechanical properties of the material, resulting in stretchable and elastic constructs without compromising cell viability and adhesion. The printed vessel structures displayed uniform wall thickness, shape retention, improved elasticity, permeability, and colonization by endothelial-derived - EA.hy926 cells. The chorioallantoic membrane (CAM) and <i>in vivo</i> assays demonstrated the hydrogel's ability to support neoangiogenesis. The hydrogel material with PEG-Tyr modification holds promise for vascular tissue engineering applications, providing a flexible, biocompatible, and functional platform for the fabrication of vascular structures.