A Systematic Review on Artificial Liver for Implantation.

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Hepatology

Background:

• Chronic liver disease is a major global health issue with limited treatment options.
• Orthotopic liver transplantation faces challenges due to organ scarcity and post-surgical complications.
• Current extracorporeal support systems offer temporary solutions but do not restore full liver function or patient autonomy.

Purpose of the Study:

• To systematically review recent advancements in implantable artificial livers (IALs) for permanent integration.
• To assess cellular sources, fabrication methods, maturation techniques, and functional readiness of IALs.
• To identify technological gaps and future directions for clinical translation of IALs.

Main Methods:

• Systematic review adhering to PRISMA 2020 guidelines.
• Analysis of 71 eligible studies on implantable artificial livers.
• Evaluation of cellular sources, scaffold materials, fabrication strategies, and functional assessments.

Main Results:

• Significant progress noted in stem-cell-derived hepatocytes and bioactive scaffolds like decellularized extracellular matrix (dECM).
• A critical gap exists in scaling prototypes from sub-centimeter to clinically relevant volumes (~200 mL).
• Challenges include vascular network integration, functional biliary systems, and achieving higher-order functions like metabolic zonation.

Conclusions:

• IAL development requires addressing engineering challenges in vascularization and biliary systems for clinical viability.
• Future research should focus on multi-cellular patterning, microfluidic maturation, and autologous cell reprogramming.
• Standardized functional benchmarks are crucial for advancing biofabricated hepatic replacement towards successful clinical application.