TY - JOUR
T1 - Decellularized Liver Matrix-Modified Cryogel Scaffolds as Potential Hepatocyte Carriers in Bioartificial Liver Support Systems and Implantable Liver Constructs
AU - Damania, Apeksha
AU - Kumar, Anupam
AU - Teotia, Arun K.
AU - Kimura, Haruna
AU - Kamihira, Masamichi
AU - Ijima, Hiroyuki
AU - Sarin, Shiv Kumar
AU - Kumar, Ashok
N1 - Funding Information:
A.D. and A.K.T. acknowledge the IIT Kanpur for their PhD program fellowship. A.K. acknowledges the DBT Tata Innovation Fellowship. The authors would like to thank all other co-workers who have contributed to this collaborative project. This work has been supported by the Department of Biotechnology (DBT), Ministry of Science and Technology, Govt. of India for Bioartificial liver (BAL) research project (project no. BT/PR1184/MED/32/105/2009). This work was also partially supported by the DBT project (project no. BT/ PR7376/MED/29/669/2012) as well as the Department of Science and Technology, DST-JSPS bilateral project (project no. DST/INT/JSPS/P-184/2014), Government of India.
PY - 2018/1/10
Y1 - 2018/1/10
N2 - Recent progress in the use of decellularized organ scaffolds as regenerative matrices for tissue engineering holds great promise in addressing the issue of donor organ shortage. Decellularization preserves the mechanical integrity, composition, and microvasculature critical for zonation of hepatocytes in the liver. Earlier studies have reported the possibility of repopulating decellularized matrices with hepatic cell lines or stem cells to improve liver regeneration. In this work, we study the versatility of the decellularized liver matrix as a substrate coating of three-dimensional cryogel scaffolds. The coated cryogels were analyzed for their ability to maintain hepatic cell growth and functionality in vitro, which was found to be significantly better than the uncoated cryogel scaffolds. The decellularized liver matrix-coated cryogel scaffolds were evaluated for their potential application as a cell-loaded bioreactor for bioartificial liver support and as an implantable liver construct. Extracorporeal connection of the coated cryogel bioreactor to a liver failure model showed improvement in liver function parameters. Additionally, offline clinical evaluation of the bioreactor using patient-derived liver failure plasma showed its efficacy in improving liver failure conditions by approximately 30-60%. Furthermore, implantation of the decellularized matrix-coated cryogel showed complete integration with the native tissue as confirmed by hematoxylin and eosin staining of tissue sections. HepG2 cells and primary human hepatocytes seeded in the coated cryogel scaffolds implanted in the liver failure model maintained functionality in terms of albumin synthesis and cytochrome P450 activity post 2 weeks of implantation. In addition, a 20-60% improvement in liver function parameters was observed post implantation. These results, put together, suggest a possibility of using the decellularized matrix-coated cryogel scaffolds for liver tissue engineering applications.
AB - Recent progress in the use of decellularized organ scaffolds as regenerative matrices for tissue engineering holds great promise in addressing the issue of donor organ shortage. Decellularization preserves the mechanical integrity, composition, and microvasculature critical for zonation of hepatocytes in the liver. Earlier studies have reported the possibility of repopulating decellularized matrices with hepatic cell lines or stem cells to improve liver regeneration. In this work, we study the versatility of the decellularized liver matrix as a substrate coating of three-dimensional cryogel scaffolds. The coated cryogels were analyzed for their ability to maintain hepatic cell growth and functionality in vitro, which was found to be significantly better than the uncoated cryogel scaffolds. The decellularized liver matrix-coated cryogel scaffolds were evaluated for their potential application as a cell-loaded bioreactor for bioartificial liver support and as an implantable liver construct. Extracorporeal connection of the coated cryogel bioreactor to a liver failure model showed improvement in liver function parameters. Additionally, offline clinical evaluation of the bioreactor using patient-derived liver failure plasma showed its efficacy in improving liver failure conditions by approximately 30-60%. Furthermore, implantation of the decellularized matrix-coated cryogel showed complete integration with the native tissue as confirmed by hematoxylin and eosin staining of tissue sections. HepG2 cells and primary human hepatocytes seeded in the coated cryogel scaffolds implanted in the liver failure model maintained functionality in terms of albumin synthesis and cytochrome P450 activity post 2 weeks of implantation. In addition, a 20-60% improvement in liver function parameters was observed post implantation. These results, put together, suggest a possibility of using the decellularized matrix-coated cryogel scaffolds for liver tissue engineering applications.
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U2 - 10.1021/acsami.7b13727
DO - 10.1021/acsami.7b13727
M3 - Article
C2 - 29210278
AN - SCOPUS:85040313486
SN - 1944-8244
VL - 10
SP - 114
EP - 126
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 1
ER -