A 3D-printable, glucose-sensitive and thermoresponsive hydrogel as sacrificial materials for constructs with vascular-like channels

Abstract A major challenge in vascular engineering is to fabricate 3D vascular constructs with proper blood circulation. In spite of the fact that many methods have been reported to generate vascular constructs, there remain some disadvantages. In this study, a boronate ester hydrogel with 3D printability and self-healing ability was prepared as sacrificial materials to tailor tubular microchannels in a non-sacrificial gel. The preparation of the hydrogel involved the copolymerization of N-isopropylacrylamide for thermoresponsiveness, with pentafluorophenyl acrylate for post-modification, and poly(vinyl alcohol) for gel formation. Besides, cellulose nanofibrils was added to facilitate 3D printing of the hydrogel. The thermoresponsiveness and printability of the hydrogel were studied by rheology. The optimized hydrogel could be successfully printed through a 30 G nozzle (inner diameter= 160 μm) by a commercial 3D bioprinter. To demonstrate the feasibility in fabricating 3D vascularized constructs, the sacrificial hydrogel was printed and a non-sacrificial gel was cast on the sacrificial hydrogel. This combined gel was immersed into culture medium to elute the sacrificial hydrogel. Interconnecting multichannels in the non-sacrificial gel were achieved in 5 min. Vascular endothelial cells (ECs) seeded were able to proliferate and attach in the microchannels of the construct. The glucose-sensitive, 3D printable sacrificial materials may create complex and easily removable 3D structures for the fabrication of precise vascularized constructs.