Current progress in hepatic tissue regeneration by tissue engineering

Abstract

Background: Liver, as a vital organ, is responsible for a wide range of biological functions to maintain homeostasis and any type of damages to hepatic tissue contributes to disease progression and death. Viral infection, trauma, carcinoma, alcohol misuse and inborn errors of metabolism are common causes of liver diseases are a severe known reason for leading to end-stage liver disease or liver failure. In either way, liver transplantation is the only treatment option which is, however, hampered by the increasing scarcity of organ donor. Over the past years, considerable efforts have been directed toward liver regeneration aiming at developing new approaches and methodologies to enhance the transplantation process. These approaches include producing decellularized scaffolds from the liver organ, 3D bio-printing system, and nano-based 3D scaffolds to simulate the native liver microenvironment. The application of small molecules and micro-RNAs and genetic manipulation in favor of hepatic differentiation of distinct stem cells could also be exploited. All of these strategies will help to facilitate the application of stem cells in human medicine. This article reviews the most recent strategies to generate a high amount of mature hepatocyte-like cells and updates current knowledge on liver regenerative medicine.

Biomaterial-based cell delivery strategies to promote liver regeneration

“…For example, the thickness of nanofibers – which can be made from synthetic, natural, or self-assembling peptides - will control cell adherence and survival [ 126 ]. Nanofibers and microspheres provide increased surface area for cell adhesion [ 127 ] and can promote 3D hepatic sheet formation [ 128 ]. Hepatic lobules are roughly hexagonal in geometry, and micropatterning techniques to fabricate scaffolds that mimic the in vivo structure of hepatic lobules can be used to culture and maintain hepatocytes with other cell types prior to transplantation [ 129 , 130 ].…”

Current Advances in 3D Tissue and Organ Reconstruction

“…Following this, many studies using a single type of tissue-specific stem cells [ 158 , 170 , 181 , 182 , 183 , 184 , 185 ] or induced pluripotent cells [ 185 , 186 , 187 , 188 ] were carried out, and others are currently ongoing, in order to identify the best 3D supports able to boost cell differentiation and successfully produce in vitro functional tissues and organs for future possible transplantation. In parallel, both synthetic and biological scaffolds were repopulated with terminally differentiated cells, including fibroblasts [ 155 ], mature hepatocytes [ 189 , 190 , 191 ], and pancreatic endocrine [ 192 , 193 , 194 ], cardiac [ 195 ], and ovarian cells [ 196 ].…”

The Synergy between Organ-on-a-Chip and Artificial Intelligence for the Study of NAFLD: From Basic Science to Clinical Research

“…Generally, a healthy human liver has a stiffness that ranges from 3 to 8 kPa which can increase about 30% when fibrosis and fibrosis-related processes are in place [ 56 ]. Overall, rigid materials, with a stiffness that resemble the fibrotic state, enhance hepatocytes attachment, proliferation, mobility, and dedifferentiation [ 57 , 58 ]. It is biological plausible because of the intense cellular recruitment that takes place surrounding the damaged/fibrotic area where a high number of undifferentiated cells are needed to replace the dead ones.…”