Microfluidic 3D printing hydrogels based on fish liver decellularized extracellular matrix for liver regeneration

Liver tissue engineering offers potential in liver transplantation, while the development of hydrogels for scalable scaffolds incorporating natural components and effective functionalities is ongoing. Here, we propose a novel microfluidic 3D printing hydrogel derived from decellularized fish liver extracellular matrix for liver regeneration. By decellularizing fish liver and combining it with gelatin methacryloyl, the hydrogel scaffold retains essential endogenous growth factors such as collagen and glycosaminoglycans. Additionally, microfluidic‐assisted 3D printing technology enables precise modulation of the composition and architecture of hydrogels to fulfill clinical requirements. Benefiting from the natural source of materials, the hydrogels exhibit excellent biocompatibility and cellular proliferation capacity for incorporating induced pluripotent stem cell‐derived hepatocytes (iPSC‐heps). Furthermore, the macroscopic architecture and biomechanical environment of hydrogels foster optimal functional expression of iPSC‐heps. Importantly, post‐transplantation, the hydrogels significantly enhance survival rates and liver function in mice with acute liver failure, promoting liver regeneration and repair. These findings suggest that microfluidic 3D printed hydrogels represent promising candidates for liver transplantation and functional recovery. Microfluidic 3D bioprinting of hydrogels from fish liver dECM and GelMA enhances liver regeneration by supporting iPSC‐hep function and significantly improving survival rates in acute liver failure models. This study presents a promising approach for liver tissue engineering and regenerative medicine.