Microfabrication and microfluidics for muscle tissue models

Abstract

The relatively recent development of microfluidic systems with wide-ranging capabilities for generating realistic 2D or 3D systems with single or multiple cell types has given rise to an extensive collection of platform technologies useful in muscle tissue engineering. These new systems are aimed at (i) gaining fundamental understanding of muscle function, (ii) creating functional muscle constructs in vitro, and (iii) utilizing these constructs a variety of applications. Use of microfluidics to control the various stimuli that promote differentiation of multipotent cells into cardiac or skeletal muscle is first discussed. Next, systems that incorporate muscle cells to produce either 2D sheets or 3D tissues of contractile muscle are described with an emphasis on the more recent 3D platforms. These systems are useful for fundamental studies of muscle biology and can also be incorporated into drug screening assays. Applications are discussed for muscle actuators in the context of microrobotics and in miniaturized biological pumps. Finally, an important area of recent study involves coculture with cell types that either activate muscle or facilitate its function. Limitations of current designs and the potential for improving functionality for a wider range of applications is also discussed, with a look toward using current understanding and capabilities to design systems of greater realism, complexity and functionality.

Human cardiac fibroblasts adaptive responses to controlled combined mechanical strain and oxygen changes in vitro

“…The elucidation of pathological cellular routes leading to tissue-level failure can clearly benefit from effective in vitro studies capable of dissecting and analyzing responses to multiple physiological and pathological conditions. Microfluidic technologies have recently enabled the development of advanced cardiac models by integrating key environmental cues in cardiac cell cultures (Agarwal et al, 2013; Marsano et al, 2016; Pavesi et al, 2015; Uzel et al, 2014). We here investigated CF behaviors in a compact multi-chamber in vitro platform designed to perform cell cultures under combined mechanical stimulation and changes in oxygen levels.…”

3D Bioprinting in Skeletal Muscle Tissue Engineering

“…However, despite significant advances in SMTE, fully functional skeletal muscle tissue constructs have not yet been fabricated in vitro. In particular, the forces generated from engineered skeletal muscle tissues are still low compared to their natural counterparts, as the in vitro muscles usually present a more immature phenotype resembling denervated muscles . To improve the functionality of engineered muscles, researchers have aimed to mimic the structure and microenvironment of skeletal muscle in vivo.…”

3D culture models of tissues under tension

“…In particular, progress has been made in developing a model for skeletal muscle (Juhas et al, 2014;Sakar et al, 2012;Uzel et al, 2014), which could be useful for understanding and modeling dystrophic muscle diseases. Constrained microtissues also have been applied to model airway smooth muscle (West et al, 2013), aortic valve tissue (Kural and Billiar, 2016) and lung (Chen et al, 2016b).…”