Biomimetic Liver Lobules from Multi-Compartmental Microfluidics.

Engineered liver lobule is highly practical in hepatic disease treatment, while constructing a 3D biomimetic lobule with a heterogeneous architecture on a large scale is challenging. Here, inspired by the natural architectural construction of hepatic lobules, biomimetic hepatic lobules are proposed with coaxially through-pores for nutrient exchange via microfluidic technology. This multi-channel microfluidic chip is made by parallelly installing capillaries. Sodium alginate (Alg) is pumped through its central channel, while Ca-loaded gelatin methacrylate (GelMA) solutions encapsulating hepatocytes, mesenchymal stem cells, and endothelia cells are pumped through surrounding channels, respectively. The rapid gelation of Alg and Ca brings about an in situ formation of Alg fiber, with heterogeneous multi-cell-laden GelMA microcarriers forming around it. The peeled-off microcarriers each featured with a coaxially through pore, simulating the cord-like structure of hepatic lobule and facilitating nutrients exchange. Meanwhile, the spatially anisotropic arrangement of cells highly simulates the hepatic architecture. It is demonstrated that by transplanting these biomimetic microparticles into liver in situ, the failed liver in rat shows increased regeneration and decreased necrosis. These results indicated that the microfluidic multi-compartmental microcarriers provide a new strategy to engineer 3D artificial livers for clinical translation.