From scaffold to function: A systematic review on dLECM-based hydrogels for liver tissue engineering - Fabrication, properties, and translational applications.

Background: Liver tissue engineering is a rapidly advancing field aiming to address the critical shortage of donor organs and improve Methods: A systematic search was conducted in accordance with PRISMA 2020 guidelines across PubMed, Scopus, Google scholar and Web of Science. A total of 74 studies were included after screening 536 records identified from databases. Data were extracted on tissue source, decellularization techniques, dECM solubilization, hydrogel formulation, crosslinking methods, physicochemical characterization, and Results: The majority of studies utilized porcine or rodent livers, with immersion/agitation and vascular perfusion as the primary decellularization methods. Sodium dodecyl sulfate (SDS), Triton X-100, and ammonium hydroxide were the most common detergents, often combined with enzymatic treatments (e.g., DNase, trypsin) to enhance nuclear removal. dLECM was predominantly solubilized using pepsin in acidic conditions (acetic acid or HCl) and reconstituted into hydrogels via thermal gelation at 37 °C. The resulting hydrogels demonstrated excellent biocompatibility, supporting high viability and enhanced functional activity-including albumin secretion, urea synthesis, and expression of hepatic markers (e.g., CYP450, CK18, AFP)-in primary hepatocytes, HepG2 cells, and stem cell-derived hepatocyte-like cells. Advanced applications such as 3D bioprinting, organoid culture, and Conclusion: dLECM-based hydrogels represent a highly promising and biomimetic platform for liver tissue engineering, capable of supporting complex cellular functions and regenerative outcomes. Despite significant progress, standardization of fabrication protocols, comprehensive physicochemical characterization, and long-term