Three-dimensional models of skeletal muscle under tension: a systematic review and core outcome set

Abstract Biologically representative three-dimensional (3D) skeletal muscle models are required to understand the mechanisms underpinning muscle disease. The primary aim of this systematic review is to evaluate the current literature on 3D skeletal muscle models under tension. Its secondary aim is to explore injury mechanisms and generate a novel Core Outcome Set (COS) for reporting of such models. In vitro studies that utilised any skeletal muscle cell types cultured with an anchor system imposing axial strain were eligible for inclusion. A modified Delphi approach using corresponding authors of included studies was then developed to obtain a COS. This systematic review was reported in compliance with the PRISMA 2020 checklist. 37 articles were included. Of these, 7 articles induced an injury in their model. Cell lines used were both human and animal. Immunohistochemical testing on models revealed greatest concordance for myosin heavy chain (MHC), alpha actinin, and Pax7 as a means of demonstrating striated muscle. The final COS agreed on multiple reporting criteria for the validation of models based on morphology, phenotype and function. This systematic review summarises the current literature and has developed core outcome reporting for models of 3D skeletal muscle that impose axial strain.