# A Systematic Review on Artificial Liver for Implantation

## TL;DR

This paper reviews recent progress in implantable artificial livers, highlighting advances in cell sources and scaffolds, while identifying key engineering challenges for clinical translation.

## Contribution

A systematic evaluation of current implantable artificial liver technologies and identification of critical gaps in scaling and functional complexity.

## Key findings

- Significant progress in stem-cell-derived hepatocytes and decellularized extracellular matrix scaffolds.
- Current prototypes remain limited to sub-centimeter sizes, requiring scaling to clinically relevant volumes.
- Key challenges include vascular network integration and functional biliary systems to prevent injury.

## Abstract

Chronic liver disease remains a leading cause of global mortality, yet organ shortages and transplant complications limit the efficacy of orthotopic liver transplantation. While extracorporeal support systems serve as temporary bridges, they fail to restore long-term patient autonomy or replicate complex biosynthetic functions. This systematic review, conducted in accordance with PRISMA 2020 guidelines, evaluates recent advancements in implantable artificial livers (IALs) designed for permanent functional integration. We analyzed 71 eligible studies, assessing cellular sources, fabrication strategies, maturation processes, and functional readiness. Our findings indicate significant progress in stem-cell-derived hepatocytes and bioactive scaffolds, such as decellularized extracellular matrix (dECM). However, a critical technological gap remains in scaling current sub-centimeter prototypes toward clinically relevant volumes (~200 mL). Key engineering challenges include integrating hierarchical vascular networks, requiring primary vessels exceeding 2 mm in diameter for surgical anastomosis, and functional biliary systems to prevent cholestatic injury. Furthermore, while micro-vascularization and protein synthesis are well documented, higher-order functions such as spatial zonation and coordinated metabolic stability remain underreported. Future clinical translation necessitates advancements in multi-cellular patterning, microfluidic-driven maturation, and autologous reprogramming. This review provides a comprehensive roadmap for bridging the gap between biofabricated constructs and organ-scale hepatic replacement, emphasizing the need for standardized functional benchmarks to ensure long-term success.