Liver regenerative medicine approaches: Translational strategies for pediatric surgery

Pediatric hepatobiliary diseases can progress to liver failure and transplantation, yet donor scarcity, lifelong immunosuppression, and cumulative graft-related morbidity remain major limitations. Regenerative medicine offers complementary strategies for disease modelling, therapeutic discovery, tissue repair, and clinical decision-making. Patient-derived organoids and microphysiological systems can reproduce disease-specific epithelial phenotypes, support drug screening, and provide mechanistic or prognostic information in conditions such as biliary atresia and inherited cholestatic disorders. Cell-based therapies may provide temporary metabolic support but remain constrained by limited engraftment and dilution during liver growth. Repeatable mRNA delivery may accommodate rapid hepatic expansion, whereas a successfully installed genomic edit may remain durable even during active hepatic proliferation. Surgical strategies, including portal vein embolization and selected partial ALPPS, exploit endogenous regeneration to increase the future liver remnant when major resection is required. In pediatric acute liver failure, extracorporeal support can provide temporary metabolic and physiological stabilization while native-liver recovery and transplant candidacy are assessed. We propose a developmental and disease-specific framework integrating structural integrity, clinical urgency and trajectory, and developmental stage. This framework is intended to guide multidisciplinary assessment of when regenerative or supportive strategies remain appropriate and when transplant evaluation should be escalated, rather than to define universal treatment thresholds.