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Yet efficiently reconstructing its hierarchical and vascular microarchitecture in vitro remains a central challenge. Here, we report a vascularized liver\u2010on\u2010a\u2010microsphere (VLOM) system that recreates lobule\u2010like structure and function within individual microscale hydrogel particles. Using a microfluidic\u2010aerosol fabrication strategy, compartmentalized microspheres with rough\u2010textured surface and built\u2010in spatial addressing markers were produced to spatially localize multiple liver cell types and support endothelial barrier formation. The VLOMs exhibit uniform morphology, structural stability, and high viability, accompanied by enhanced hepatic performance, including elevated albumin and urea synthesis and upregulated CYP2B6 and CYP3A4 expression. Metabolomic profiling reveals activation of the alanine\u2010glucose metabolic cycle, which strengthens biosynthetic and detoxification capacities. Supplementation with alanine or glucose further restores hepatic function and mitigates rifampicin\u2010induced hepatotoxicity, underscoring the protective role of this cycle in maintaining metabolic resilience. This scalable, vascularized microsphere system unites microengineering precision and physiological fidelity, offering a high\u2010throughput route to model liver metabolism and evaluate drug responses.<\/jats:p>","DOI":"10.1002\/advs.76211","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:16:27Z","timestamp":1783347387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vascularized Liver\u2010on\u2010a\u2010Microsphere Reveals Alanine\u2010Glucose Metabolism\u2010Driven Regulation of Liver Function and Injury"],"prefix":"10.1002","volume":"13","author":[{"given":"Jingyang","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu 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