An organoid tissue patch preserves regenerative permissiveness at the remnant-liver boundary after hepatectomy

Background: Early recovery after major hepatectomy may depend not only on remnant liver volume, but also on whether the injury-adjacent remnant-liver boundary can withstand the narrow postoperative convergence of mechanical disruption, inflammatory amplification, and transient metabolic insufficiency that may otherwise divert the remnant liver away from productive regeneration.Methods: We engineered an organoid tissue patch (OTP) by integrating matrix-free expanded human bile-derived liver organoids with a reticulated microfibrous scaffold for localized deployment on the remnant liver surface.OTP was evaluated in a murine 70% partial hepatectomy model using survival, serum biochemical, histological, and molecular analyses, together with pharmacologic PPARα inhibition.Results: OTP treatment was associated with improved survival and biochemical recovery, together with attenuated tissue injury in the predefined patch-placement region.At Day 3, OTP-treated tissue showed reduced NF-κB-linked inflammatory activity, lower inflammatory mediator expression, and an increased CD206-associated macrophage signal.Metabolism-and proliferationrelated programs were concurrently enriched, accompanied by increased PPARα immunoreactivity, YAP-positive nuclei, and hepatocyte proliferative entry.Systemic PPARα inhibition partially attenuated these effects, supporting a functional contribution of PPARα-responsive signaling.Conclusions: These findings support localized OTP deployment as a strategy to provide temporary bioactive support to the vulnerable remnant-liver boundary during endogenous recovery, without evidence of bulk donor tissue replacement.