Vascularized Liver-on-a-Microsphere Reveals Alanine-Glucose Metabolism-Driven Regulation of Liver Function and Injury
Background
The hepatic lobule relies on the spatial arrangement of multiple cell types to coordinate metabolism, detoxification, and immune regulation, but it is difficult to reproduce both its hierarchical structure and vascular interface in vitro. 2D culture lacks three-dimensional signals; organoids and spheroids face limits in reproducibility, maturation time, and diffusion. Microfluidics can assemble cells but often encapsulates them randomly and lacks a vascular barrier and zonation control. The target direction is a lobule-like, vascularized, addressable microscale model for metabolic pathway and drug-response studies.
Innovation
Combining microfluidics with aerosol generates six-compartment alginate microspheres with rough surfaces and spatial addressing markers. Different chambers contain HepG2, LX-2, and THP-1 cells, while Matrigel-induced HUVEC cells form an endothelial layer outside, mimicking a semipermeable hepatic sinusoid interface. Metabolomics identifies the alanine-glucose cycle. Alanine or glucose supplementation restores albumin and urea indicators and alleviates rifampicin-induced stress changes. The target is alanine-glucose metabolic coupling and the vascularized microenvironment.
Materials
The core material is alginate hydrogel. CaCl₂ aerosol locally crosslinks the droplet surface, forming crater-like roughness that supports Matrigel adsorption and endothelial spreading. Microspheres are uniform, with CV below 4% and viability above 98% at five days, remaining above 80% in long-term culture. FITC-dextran shows the endothelial layer allows small molecules to pass while restricting 40-150 kDa macromolecules, indicating size-selective semipermeability. The material and structure together target a vascularized interface, spatial compartmentalization, and metabolic microenvironment reconstruction.
Note: This is only a frontier update and does not constitute any related advice.
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DOI: 10.1002/advs.76211