Abstract
Microphysiological systems provide a tool to simulate normal and pathological function of organs for prolonged periods. These systems must incorporate the key functions of the individual organs and enable interactions among the corresponding microphysiological units. The relative size of different microphysiological organs and their flow rates are scaled in proportion to in vivo values. We have developed a microphysiological three-dimensional engineered human skeletal muscle system connected to a circulatory system that consists of a tissue-engineered blood vessel as part of a high-pressure arterial system. The engineered human skeletal muscle tissue reproduces key mechanical behaviors of skeletal muscle in vivo. Pulsatile flow is produced using a novel computer-controlled magnetically activated ferrogel. The system is versatile and the muscle unit can be integrated with other organ systems. Periodic monitoring of biomechanical function provides a non-invasive assessment of the health of the tissue and a way to measure the response to drugs and toxins.
Highlights
In vitro microphysiological multiorgan systems using human cells provide a novel method to identify promising drug candidates [1]
The onset and progression of sarcopenia is a strong predictor of mortality and prevalence increases with advancing age [4]
Type 2 diabetes or lowgrade inflammation is more common in individuals who have sarcopenia [5]
Summary
In vitro microphysiological multiorgan systems using human cells provide a novel method to identify promising drug candidates [1]. Myoblasts were obtained from biopsies of the vastus lateralis of healthy middle-aged volunteers, endothelial cells were cultured from blood-derived late outgrowth endothelial progenitor cells in human umbilical cord blood [10], and vessel wall medial cells were either human dermal fibroblasts or mesenchymal stem cells These individual units are cultured separately for about 2 weeks to enable the skeletal myoblasts to fuse and differentiate and to allow the blood vessels to develop sufficient mechanical strength. Optimization of the dimensions of the muscle bundles, the media and hydrogel composition, the cell density, and the differentiation procedure (Figure 1) resulted in three-dimensional human muscle bundles with highly aligned, cross-striated myofibers containing myogenin-positive nuclei and acetylcholine receptor clusters (Figure 2b1) Functional properties of such engineered muscle were tested using standard force test protocols [17]. Cell Sourcing Muscle - Optimize isolation, culture and differentiation of primary cells
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