Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation

Da-Hyun Kim, Min-Ji Kim, Seon-Yeong Kwak, Jaemin Jeong, Dongho Choi, Soon Won Choi, Jaechul Ryu and Kyung-Sun Kang ()
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Da-Hyun Kim: Seoul National University
Min-Ji Kim: Seoul National University
Seon-Yeong Kwak: Seoul National University
Jaemin Jeong: Hanyang University College of Medicine
Dongho Choi: Hanyang University College of Medicine
Soon Won Choi: Seoul National University
Jaechul Ryu: Seoul National University
Kyung-Sun Kang: Seoul National University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Decellularized extracellular matrix scaffold, widely utilized for organ engineering, often undergoes matrix decomposition after transplantation and produces byproducts that cause inflammation, leading to clinical failure. Here we propose a strategy using nano-graphene oxide to modify the biophysical properties of decellularized liver scaffolds. Notably, we demonstrate that scaffolds crosslinked with nano-graphene oxide show high resistance to enzymatic degradation via direct inhibition of matrix metalloproteinase activity and increased mechanical rigidity. We find that M2-like macrophage polarization is promoted within the crosslinked scaffolds, which reduces graft-elicited inflammation. Moreover, we show that low activities of matrix metalloproteinases, attributed to both nano-graphene oxide and tissue inhibitors of metalloproteinases expressed by M2c, can protect the crosslinked scaffolds against in vivo degradation. Lastly, we demonstrate that bioengineered livers fabricated with the crosslinked scaffolds remain functional, thereby effectively regenerating damaged livers after transplantation into liver failure mouse models. Overall, nano-graphene oxide crosslinking prolongs allograft survival and ultimately improves therapeutic effects of bioengineered livers, which offer an alternative for donor organs.

Date: 2023
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DOI: 10.1038/s41467-023-35941-2

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