PRP-driven biomimetic liver tissue engineering: A cost-effective platform for high-efficiency expansion of mouse primary hepatocytes.

Three-dimensional (3D) scaffold-based culture systems offer a promising approach for expanding primary hepatocytes in vitro, potentially overcoming donor shortages in liver failure treatment. In this study, we designed a multifunctional Alg1SBC scaffold that actively loads and activates platelet-rich plasma (PRP) as a bioinspired platform. This system effectively combines low-cost PRP with a dual-network matrix composed of alginate (Alg) and sulfonated bacterial cellulose (SBC). The negatively charged surface of the Alg1SBC scaffold mimics the electrostatic characteristics of hepatic sinusoids, facilitating efficient PRP adsorption and sustained release of growth factors. Importantly, calcium ions not only crosslinked the scaffold to mimic liver-like mechanical stiffness but also activated PRP through a thrombin-independent mechanism, thereby promoting the controlled release of autologous growth factors. In mouse model of liver failure, the PRP-functionalized Alg1SBC scaffold improved primary hepatocyte engraftment, accelerated the formation of a functional hepatic niche, and prolonged survival. These findings represent a significant advance in scaffold-guided regenerative therapy for liver failure, underscoring the clinical potential of PRP-activated biomimetic systems in hepatology.