Re-Endothelialization of Decellularized Liver Scaffolds: A Step for Bioengineered Liver Transplantation

Abstract

Bioengineered livers (BELs) are an attractive therapeutic alternative to address the donor organ shortage for liver transplantation. The goal of BELs technology aims at replacement or regeneration of the native human liver. A variety of approaches have been proposed for tissue engineering of transplantable livers; the current review will highlight the decellularization-recellularization approach to BELs. For example, vascular patency and appropriate cell distribution and expansion are critical components in the production of successful BELs. Proper solutions to these components of BELs have challenged its development. Several strategies, such as heparin immobilization, heparin-gelatin, REDV peptide, and anti-CD31 aptamer have been developed to extend the vascular patency of revascularized bioengineered livers (rBELs). Other novel methods have been developed to enhance cell seeding of parenchymal cells and to increase graft functionality during both bench and in vivo perfusion. These enhanced methods have been associated with up to 15 days of survival in large animal (porcine) models of heterotopic transplantation but have not yet permitted extended survival after implantation of BELs in the orthotopic position. This review will highlight both the remaining challenges and the potential for clinical application of functional bioengineered grafts.

Application of Acellular Dermal Matrix in Gynaecology—A Current Review

“…The immune response is mainly directed against the proteins and lipids of cell membranes; thus, cell extraction from tissue is a promising method to avoid the creation of a post-transplant immune response in the body of the recipient [ 4 , 12 , 13 , 14 , 15 , 16 ]. The removal of cellular components should minimize the immunologically induced inflammatory process, which may weaken the biodegradation process of the transplanted bioprosthesis [ 15 ].…”

“…The procedure of removing cells from allogeneic human dermis results in a cell-free, non-immunogenic matrix composed of extracellular matrix (ECM) elements that can be re-inhabited by autologous cells. Such cell-free dermal matrices (ADMs) can also stimulate natural regenerative and reconstructive mechanisms [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

“…Based on the results of numerous studies, it has also been shown that cell-free ECM scaffolds are able to propagate and support the growth and differentiation of many types of cells in vitro and induce constructive tissue remodelling processes after in vivo transplantation [ 7 , 8 , 9 , 10 , 11 ]. Thus, the use of three-dimensional ECM scaffolds obtained from tissues or whole organs that have undergone cell removal procedures is an increasingly used strategy of regenerative medicine and tissue engineering [ 4 , 5 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

The Influence of Interdisciplinary Work towards Advancing Knowledge on Human Liver Physiology

“…Once the liver is cell-free and the ECM is well preserved, a bioengineered liver must accomplish the following properties: a proper vascular permeability to distribute new cells in the right location, reseeded cells that can be of parenchymal (hepatocytes) or non-parenchymal type (e.g., hepatic stellate cells, endothelial cells), and the provision of oxygen and nutrients supporting cell viability. Although scientists have implemented several strategies to solve these issues, to date only short graft survival has been reached [ 73 ]. The additional technical problems that are still under intense research are those related to maintaining hepatocytes in a differentiated state.…”

Angiogenesis and Re-endothelialization in decellularized scaffolds: Recent advances and current challenges in tissue engineering

“…Tissue engineering and regenerative medicine, aiming to design, produce, and achieve an efficient and functional organ, play a crucial role in overcoming immunity limitations and transplantation obstacles ( Ahmadi et al, 2022 ; Li et al, 2022a ; Cox-Pridmore et al, 2022 ). Decellularization and recellularization (D&R) of tissues and organs are efficient alternatives to classic organ transplantation ( Dias et al, 2022 ).…”