Engineering Modular 3D Liver Culture Microenvironments In Vitro to Parse the Interplay between Biophysical and Biochemical Microenvironment Cues on Hepatic Phenotypes

Abstract

The liver is the largest solid organ in the body and is responsible for hundreds of functions, including nutrient and xenobiotic/drug metabolism, serum protein production, nutrient storage, and immune system response. [1] Models of these processes in both healthy and diseased states, as well as their responses to therapeutic interventions, are of intense interest in drug discovery and development. [2][3][4] The increasing commercial availability and utility of human donor liver cells are driving the advancement of in vitro models of human liver, supplementing animal models that fail to capture the full complexity of human liver phenotypes. [3][4][5] An evergrowing number of in vitro liver model applications involve aspects of liver immune responses. [6][7][8][9] Such responses are mediated not just by cells classically associated with the immune system but also by hepatocytes and other nonparenchymal cells, which all produce immunemodulating signaling molecules. It is thus crucial to consider how the in vitro microenvironment regulates the potential for hepatocytes and other cell types to respond to perturbations, which may then, in turn, influence other metabolic, [6] toxicity, [10] and disease

Editorial Comment: Selected Proceedings From the 2022 International Society of Limb Salvage Meeting

“…She brought futuristic design, synthesis of scaffolds of materials, and trafficked cells under mechanical stimulation to establish neo-organs. This interdisciplinary work has yielded the powerful “Human Physiome on a Chip.” For example, improving 3D manufacturing processes has enabled the production of complex circulatory and cellular organization of a model liver [5]. These developments in regenerative medicine have been slow to be adapted in the orthopaedic world but are now ripe for introduction into limb preservation clinical trials.…”