Development of a Mechanically Active Biomaterial for Muscle Tissue Engineering

Skeletal muscle cells exist in the body in highly mechanically dynamic environments, applying forces to the extracellular matrix (ECM) and experiencing extracellular forces transmitted back to them via cell adhesion receptors such as integrins. These forces have been demonstrated in vivo and clinically to be critical to normal muscle growth and function, yet the incorporation of mechanics into the study of muscle cell biology has been limited, due at least in part to the need for complex instrumentation to apply such forces to cell culture systems. To this end, we develop novel methods for mechanically dynamic cell culture in 2D, both on glass and on soft hydrogels, using a near infrared (NIR) light-actuated mechanism: the optomechanical actuator (OMA). OMAs are photothermally responsive nanoparticles that shrink in size when illuminated with NIR light. In Aim 1, we create a cell culture surface of OMAs modified with cell adhesion ligands, and use these responsive 2D surfaces to show unprecedented spatiotemporal resolution of myoblast mechanical stimulation, demonstrating enhancement of myogenic markers after shorter stimulation time and length scales than previously reported in by other methods. In Aim 2, we further develop this technique, developing a composite, mechanically active hydrogel biomaterial by conferring NIR responsivity to a biopolymer matrix of gelatin and laminin through the incorporation of OMAs. We demonstrate this ability of this material to enhance myogenesis in myoblast cell culture, as well as to mimic the beneficial effects of exercise in vitro in a chronic inflammation model. This thesis has resulted in novel methods and materials for the application of dynamic forces in vitro, which have broad future applications in cell biology and tissue engineering.

Date

2022-01-14

Resource Type

Text

Resource Subtype

Dissertation

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