Cellularized biosynthetic microhydrogel polymers for intravascular liver tissue regeneration therapy

Area of Science:

• Biomaterials Science
• Hepatocyte Transplantation
• Tissue Engineering

Background:

• Liver transplantation faces challenges due to low hepatocyte engraftment efficiency.
• Cell-laden microhydrogels using PEGylated fibrinogen offer a potential solution as a cell carrier for intravascular transplantation.
• This method may mitigate shear stress and immunological pressure, providing a supportive biomatrix.

Purpose of the Study:

• To assess the in vitro viability and function of HuH-7 cells within PEGylated fibrinogen-hydrogels.
• To evaluate the in vivo engraftment efficiency of cell-laden microhydrogels after intraportal transplantation in rats.

Main Methods:

• In vitro analysis of HuH-7 cell viability (PI/FDA, MTT assays) and function (albumin production, CYP1A activity) within hydrogels.
• Fabrication of cell-laden microhydrogels for intraportal transplantation.
• In vivo engraftment assessment using qPCR (SRY gene) and histology at 21 days post-transplantation.

Main Results:

• In vitro cell viability in hydrogels was comparable to free cells within 48 hours, with a slight decrease after 72 hours.
• Hydrogel-encapsulated cells maintained comparable CYP1A activity and showed increased albumin concentration compared to free cells.
• Cell-laden microhydrogels demonstrated significantly higher engraftment efficiency (54.6%) compared to isolated cells (1.8%) at 21 days post-transplantation.

Conclusions:

• HuH-7 cell viability and function are well-maintained within PEGylated fibrinogen hydrogels.
• Cell-laden microhydrogels significantly enhance long-term survival and engraftment of intravascularly transplanted adult hepatocytes.
• Further optimization is needed to improve the overall efficiency of this transplantation procedure.