한빛사 논문
Da-Hyun Kim1, Min-Ji Kim1, Seon-Yeong Kwak2,3, Jaemin Jeong4, Dongho Choi4, Soon Won Choi1,5, Jaechul Ryu1,5 & Kyung-Sun Kang1,3
1Adult Stem Cell Research Center and Research Institute for Veterinary Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
2Department of Agriculture, Forestry and Life Science, College of Agriculture and Life Science, Seoul National University, Seoul 08826, Republic of Korea.
3Bio-MAX Institute, Seoul National University, Seoul 08826, Republic of Korea.
4Department of Surgery, Hanyang University College of Medicine, Seoul 04763, Republic of Korea.
5Institute of Bio & Nano Convergence, Biogo Co., LTD, Seoul 08826, Republic of Korea
Corresponding author: Correspondence to Kyung-Sun Kang.
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.
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