한빛사논문
Sayan Deb Duttaa, Keya Gangulya, Aayushi Randhawaa,b, Tejal V. Patila,b, Dinesh K. Patelc, Ki-Taek Lima,b,c,d
aDepartment of Biosystems Engineering, Kangwon National University, Chuncheon, 24341, Republic of Korea
bInterdisciplinary Program in Smart Agriculture, Kangwon National University, Chuncheon, 24341, Republic of Korea
cInstitute of Forest Sciences, Kangwon National University, Chuncheon, 24341, Republic of Korea
dBiomechagen Co., Ltd., Chuncheon, 24341, Republic of Korea
Corresponding author: Ki-Taek Lim
Abstract
In recent years, three-dimensional (3D) bioprinting of conductive hydrogels has made significant progress in the fabrication of high-resolution biomimetic structures with gradual complexity. However, the lack of an effective cross-linking strategy, ideal shear-thinning, appropriate yield strength, and higher print fidelity with excellent biofunctionality remains a challenge for developing cell-laden constructs, hindering the progress of extrusion-based 3D printing of conductive polymers. In this study, a highly stable and conductive bioink was developed based on polypyrrole-grafted gelatin methacryloyl (GelMA-PPy) with a triple cross-linking (thermo-photo-ionically) strategy for direct ink writing-based 3D printing applications. The triple-cross-linked hydrogel with dynamic semi-inner penetrating polymer network (semi-IPN) displayed excellent shear-thinning properties, with improved shape fidelity and structural stability during 3D printing. The as-fabricated hydrogel ink also exhibited “plug-like non-Newtonian” flow behavior with minimal disturbance. The bioprinted GelMA-PPy-Fe hydrogel showed higher cytocompatibility (93%) of human bone mesenchymal stem cells (hBMSCs) under microcurrent stimulation (250 mV/20 min/day). Moreover, the self-supporting and tunable mechanical properties of the GelMA-PPy bioink allowed 3D printing of high-resolution biological architectures. As a proof of concept, we printed a full-thickness rat bone model to demonstrate the structural stability. Transcriptomic analysis revealed that the 3D bioprinted hBMSCs highly expressed gene hallmarks for NOTCH/mitogen-activated protein kinase (MAPK)/SMAD signaling while down-regulating the Wnt/β-Catenin and epigenetic signaling pathways during osteogenic differentiation for up to 7 days. These results suggest that the developed GelMA-PPy bioink is highly stable and non-toxic to hBMSCs and can serve as a promising platform for bone tissue engineering applications.
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