In vivo skeletal muscle comprises bundles of highly aligned and differentiated post-mitotic multinucleated fibers, which are organized in a hierarchical manner within an extracellular matrix (ECM). Such increases would represent a significant step forward when using primary human tissue as a cell source for the study of muscle physiology and disease in TE models. The same number of cells could, however, be used to generate over 50 times this number of constructs. In many current TE skeletal muscle hydrogels, a single human microbiopsy would supply viable cells that generate ~10 constructs. Therefore, a model that is reproducible when scaling down cell number is fundamental in generating high-powered experiments using primary human derived cells. However, many current models are not amenable to incorporation of primary human tissue, which are often limited in experimental throughput due to the complexities associated with recruiting tissue donors, donor specific variations, as well as cellular senescence associated with continued passaging. Tissue engineering (TE) offers an alternative experimental platform to investigate skeletal muscle development and post-natal adaptation and function. As such, establishing a highly biomimetic model that accurately represents the native in vivo function is of paramount importance. However, investigating the cellular and molecular mechanisms that regulate muscle function in vivo is problematic, with clear experimental limitations associated with both in vivo human and animal models ( Friedmann-Bette et al., 2012). Physiologically representative models of skeletal muscle development, regeneration and adaptation will underpin the next generation of understanding regarding the pathophysiological characteristics regarding health and disease in this tissue. This research provides a strategy to overcome limited biopsy cell numbers, enabling high throughput screening of functional human tissue. To this end, a scalable model has been developed (25–500 μL construct volumes) allowing fabrication of mature primary human skeletal muscle. Many existing models are bespoke causing variability when translated between laboratories. This research presents a method using fused deposition modeling (FDM) and laser sintering (LS) 3D printing to generate reproducible and scalable tissue engineered primary human muscle, possessing aligned mature myotubes reminiscent of in vivo tissue. Current models are limited by low throughput due to the complexities associated with recruiting tissue donors, donor specific variations, as well as cellular senescence associated with passaging. The fabricated model must resemble characteristics of in vivo tissue and incorporate cost-effective and high content primary human tissue. Tissue engineered skeletal muscle allows investigation of the cellular and molecular mechanisms that regulate skeletal muscle pathology. 3University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.2Institute of Orthopaedics and Musculoskeletal Sciences, RNOH, University College London, London, United Kingdom.1School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, United Kingdom.
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