High-Content Drug Screening with Engineered Musculoskeletal Tissues

Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo

“…Together, these results lay a foundation for novel in vitro and in vivo studies of skeletal muscle function, regeneration, and vasculogenesis and provide a blueprint for future engineering of 3D functional human muscle microtissues for drug and toxicology studies (4,40).…”

“…The ability to create engineered muscle tissues that mimic the structural, functional, and regenerative properties of native muscle would enable design of accurate in vitro models for studies of muscle physiology and development (3,4) and promote cell-based therapies for muscle injury and disease (5,6). Pioneering studies of Vandenburgh and coworkers (7) and Dennis and Kosnik (8) were the first to demonstrate in vitro engineering of functional mammalian muscle constructs, followed by other studies reporting that differentiated engineered muscle can survive and vascularize upon implantation in vivo (9)(10)(11)(12)(13).…”

Rapid Prototyping of Engineered Heart Tissues through Miniaturization and Phenotype-Automation

“…However, in these micro-scale tissues, it is yet to be determined if there is an improvement of the statistical significance of functional data over that from single cells. At present, ETs in millimeter scale have been used for the functional assays with relatively good data reproducibility [8] [9]. By using ETs, a statistically significant data can be obtained using only 4-8 samples [9] instead of collecting ranging 60-600 data points per well in cell-based assays [10].…”

“…Each EHT is fabricated by pouring a gel solution containing predefined concentrations of cells, matrix proteins, and growth factors into a precisely machined well [5]. Since 1993, similar engineered tissues have been used as a model system to study signal transduction pathways that regulate contractility of fibroblasts [37], smooth muscle cells, skeletal muscle cells [8]. We were the first to introduce the use of tissue models to determine effective drug doses [38] and have recently extended the application of this technology to include phenotypic screening [39].…”

A contactless electrical stimulator: application to fabricate functional skeletal muscle tissue

“…Muscle tissue engineering has recently been suggested as a promising method to regenerate or recover damaged muscle tissues (Hinds et al 2011;Koning et al 2009). Engineered muscle tissues also have in vitro applications, such as for drug screening (Ghaemmaghami et al 2012;Vandenburgh 2009) or as engineered bio-actuators Fujita et al 2011).…”