Vasculature reconstruction of decellularized liver scaffolds via gelatin‐based re‐endothelialization

Abstract

Decellularized liver scaffolds based liver engineering is a promising approach toward developing functional liver surrogates. However, a major obstacle to long‐term transplantation is the hemocompatibility of the bioengineered liver surrogates. One approach to improve the hemocompatibility of engineered liver surrogates is re‐endothelialization. In the current study, immortalized endothelial cells were perfused for re‐endothelialization of decellularized rat liver scaffolds. When compared to the media‐based perfusion approach, gelatin hydrogels‐based perfusion significantly increased the number of cells that were retained in the decellularized liver scaffolds and the vascular lumen coverage ratio. Endothelial cells were lining along the vasculatures of the decellularized liver scaffolds and actively proliferating. Re‐endothelialization improved the blood retention ability of the liver scaffold vasculatures. Doppler ultrasound detected active blood flows within the re‐endothelialized liver scaffold transplants 8 days post‐transplantation. Our results strengthened the feasibility of developing bioengineered liver surrogates utilizing decellularized liver scaffolds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 392–402, 2019.

Strategies based on organ decellularization and recellularization

“…No recellularization protocol has achieved the combination of all of these components. Several studies have reported the successful implantation of repopulated decelluarized liver grafts . At 40 days, Yang et al .…”

Advances in Hepatic Tissue Bioengineering with Decellularized Liver Bioscaffold

“…The association with extracellular matrix components can also increase the efficiency of reendothelization. Recently, immortalized endothelial cells were utilized in a proof-of-concept study that demonstrated that the association with gelatin enhances reendothelization of a decellularized liver scaffold [40]. The attachment of endothelial cells was also improved by conjugation with a biopolymer, REDV-ELP, which was able to increase reendothelization of a rat decellularized liver bioscaffold [41].…”

Cell Therapy and Bioengineering in Experimental Liver Regenerative Medicine: In Vivo Injury Models and Grafting Strategies

“…However, many complications are related to the decellularization process, including the loss of some native critical components and bioactive molecules. Many studies have investigated how to improve the structural properties of acellular scaffolds through conjugation with crosslinking agents or extracellular matrix (ECM) particles or by improving their functionality with modifying agents that could increase cellular attachment and hemocompatibility, such as CD31, REDV peptide, fibronectin, heparin, and gelatin [80,84,93,[101][102][103][104][105]. One study used mice and pig livers that were partially hepatectomized and maintained a few days in vivo before being harvested and decellularized to generate hepatic acellular scaffolds in an active regenerative state.…”

“…The native liver-derived ECM can be used as an intact scaffold for further orthotropic or heterotopic transplantation [102,107,108]. There are different forms of acellular ECM, including hydrogel, powder, and sheet tissue papers.…”