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New Natural Polymer-based Bioinks and their 3D Bioprinting for Liver Tissue Engineering
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1  Department of Mechanical Engineering, Faculty of Engineering, The University of Hong Kong, Hong Kong, 999077, China
Academic Editor: Lidy Fratila-Apachitei

Abstract:

Liver failures caused by disease or injury are a growing medical problem globally. Currently, liver transplantation is the only viable treatment for severely compromised liver. But the scarcity of donor organs heavily limits liver transplantation. Liver tissue engineering (LTE) emerges and has shown great potential for treating liver failure. 3D bioprinting, a powerful biomanufacturing platform, can create complex cell-laden living structures for functional liver tissue regeneration, and developing new bioinks underpins advances of bioprinting in LTE. In this study, new dual-photocrosslinkable hydrogel bioinks were formulated and evaluated for LTE bioprinting. The bioinks combined glycidyl methacrylate-modified hyaluronic acid (HA-GMA), gelatin methacryloyl (GelMA) and gelatin and leveraged the synergy of these three polymer constituents for the hydrogels. HA-GMA and GelMA are UV-curable and allow mimicry of liver extracellular matrix and also precise adjustment of hydrogel modulus via photocrosslinking, thereby ensuring structural stability of bioprinted LTE constructs. GelMA provides good printability, while HA-GMA’s high degree of functionalization allows incorporation of bioactive molecules. Gelatin has dual roles: promoting cell adhesion and serving as a thermosensitive component that dissolves during service to create porous structs, thus facilitating cell infiltration, nutrient diffusion, and waste removal in a conducive cell growth microenvironment. Using tri-component hydrogel based-bioinks containing NCTC1469 mouse hepatocytes, 3D cell-scaffold constructs of the designed grid structure with square pores were fabricated via extrusion-based 3D bioprinting. By systematically varying concentrations of HA-GMA, GelMA and gelatin in hydrogel printing inks, the rheological behaviour, printability and crosslinking of inks were optimized and consequently high scaffold fidelity was attained. Additionally, mechanical properties and biodegradation behaviour of 3D printed structures could be tuned. The 3D bioprinted constructs maintained structural integrity over extended culture periods and supported high cell viability and proliferation. Importantly, the constructs promoted the expression of mature hepatic markers and sustained key liver-specific functions in vitro.

Keywords: bioprinting; biomaterials; polymer
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