Modeling Idiopathic Inflammatory Myopathy in the Bioinspired Muscle Tissue on Chip

This work proposes a new strategy to propose a vascularized muscle tissue which exhibits good muscle functions and structure. Through recirculating perfusion of activated monocytes for co-culture, the key pathological alterations of IIM are successfully replicated in vitro. The model provides a valuable tool for the studies of myopathies and drug testing.

Abstract

Idiopathic inflammatory myopathy (IIM) is an autoimmune disease that characterized by non-purulent inflammation of the skeletal muscle. However, due to the limitation of study model that can recapitulate the complex pathological process of IIM, the pathogenesis of IIM is still not fully clear. This manuscript develops a vascularized muscle tissue model on a chip that allows to model the immunity mediated pathological changes in IIM. This vascularized muscle model is constructed by layer-by-layer assembly, which could coculture of endothelial cells, myoblasts, and monocytes in a perfusable 3D system. The vascularized muscle model exhibits good biofunctions, including muscle cells alignment and fusion, myofibers generation, force production and expression of muscular biomarkers (myosin heavy chains 1, myosin heavy chains 7, actinin alpha 2, myogenin, and Desmin). Exposure to perfusion of activated monocytes, this work observes the functional changes of muscle tissue, which referred to myofibers atrophy, inflammatory response, and downregulated expression of muscle mature marker, consistent with clinical features of IIM. This work provides a unique platform for modelling IIM and paves a promising avenue for myopathies study and drug testing.