Drug‐screening platform based on the contractility of tissue‐engineered muscle

Abstract

A tissue-based approach to in vitro drug screening allows for determination of the cumulative positive and negative effects of a drug at the tissue rather than the cellular or subcellular level. Skeletal muscle myoblasts were tissue-engineered into three-dimensional muscle with parallel myofibers generating directed forces. When grown attached to two flexible micro-posts (mu posts) acting as artificial tendons in a 96-well plate format, the miniature bioartificial muscles (mBAMs) generated tetanic (active) forces upon electrical stimulation measured with a novel image-based motion detection system. mBAM myofiber hypertrophy and active force increased in response to insulin-like growth factor 1. In contrast, mBAM deterioration and weakness was observed with a cholesterol-lowering statin. The results described in this study demonstrate the integration of tissue engineering and biomechanical testing into a single platform for the screening of compounds affecting muscle strength.

Generation and Use of Cultured Human Primary Myotubes

“…In line with enhanced myotube diameter, Huang et al, (2005) showed that treatment with the trophic factor insulin-like growth factor 1 significantly increased force production of myooids. In further research insulin-like growth factor 1 was shown to induce myotube hypertrophy which was associated with a concomitant increase in active force production (Vandenburgh et al, 2008). This further supports the notion that extracellular paracrine factors are also important in enhancing construct formation.…”

“…Three-dimensional skeletal muscle tissue constructs provide a useful model for the study of muscle structure and function in physiological and pathophysiological states, drug screening and gene therapy despite current limitations in their fabrication (Bach et al, 2004;Vandenburgh, 2010;Vandenburgh et al, 2008). The use of three-dimensional constructs provides a method with enhanced physiological relevance due to the relative absence of cellular monolayers within their endogenous micorenvironments.…”

Morphogenesis of 3D vascular networks is regulated by tensile forces

“…A coculture of fibroblasts and endothelial cells (ECs) was seeded within fibrin gel fabricated uniaxially between two polydimethylsiloxane (PDMS) μposts (Fig. S1A) (23). The visually observed effects were quantified by application of a custom-designed image analysis program, based on the Hough transform function in Matlab, to calculate the orientation of the vessel structures (Fig.…”

Prospectus of cultured meat—advancing meat alternatives

“…It is a powerful technique that is mainly being designated for regenerative medicine in a wide variety of tissues and organs (Bach et al 2003;Mol et al 2005). In particular, tissue engineering of skeletal muscle has many applications, ranging from in vitro model systems for drug-screening (Vandenburgh et al 2008), pressure sores (Gawlitta et al 2007) and physiology to in vivo transplantation to treat muscular dystrophy and muscular defects (Boldrin et al 2008). Obviously, tissue engineering could also be employed for the in vitro production of skeletal muscle tissue from farm animals for consumption purposes (Edelman et al 2005).…”