The Importance of Biophysical and Biochemical Stimuli in Dynamic Skeletal Muscle Models

Abstract

Classical approaches to engineer skeletal muscle tissue based on current regenerative and surgical procedures still do not meet the desired outcome for patient applications. Besides the evident need to create functional skeletal muscle tissue for the repair of volumetric muscle defects, there is also growing demand for platforms to study muscle-related diseases, such as muscular dystrophies or sarcopenia. Currently, numerous studies exist that have employed a variety of biomaterials, cell types and strategies for maturation of skeletal muscle tissue in 2D and 3D environments. However, researchers are just at the beginning of understanding the impact of different culture settings and their biochemical (growth factors and chemical changes) and biophysical cues (mechanical properties) on myogenesis. With this review we intend to emphasize the need for new in vitro skeletal muscle (disease) models to better recapitulate important structural and functional aspects of muscle development. We highlight the importance of choosing appropriate system components, e.g., cell and biomaterial type, structural and mechanical matrix properties or culture format, and how understanding their interplay will enable researchers to create optimized platforms to investigate myogenesis in healthy and diseased tissue. Thus, we aim to deliver guidelines for experimental designs to allow estimation of the potential influence of the selected skeletal muscle tissue engineering setup on the myogenic outcome prior to their implementation. Moreover, we offer a workflow to facilitate identifying and selecting different analytical tools to demonstrate the successful creation of functional skeletal muscle tissue. Ultimately, a refinement of existing strategies will lead to further progression in understanding important aspects of muscle diseases, muscle aging and muscle regeneration to improve quality of life of patients and enable the establishment of new treatment options.

Bioinspired electrospun dECM scaffolds guide cell growth and control the formation of myotubes

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Engineering Biomimetic Materials for Skeletal Muscle Repair and Regeneration

“…The mechanical properties and chemical composition (e.g., degradation rate, stiffness/rigidity) generally can be more precisely controlled in synthetic polymers, compared to naturally derived biomaterials, and some synthetic polymers can also be made electrically conductive . However, some disadvantages include challenges in cellular attachment, the potential degradation into byproducts that impedes regeneration, and the potential formation of fibrous capsules due to an inflammatory response …”

“…[43, 44] However, some disadvantages include challenges in cellular attachment, the potential degradation into byproducts that impedes regeneration, and the potential formation of fibrous capsules due to an inflammatory response. [45]…”

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“…In order to investigate the basic functions of the nervous system and the pathogenic mechanisms of neurological disorders, it is of paramount importance to understand how molecular, physical and biochemical cues modulate the neuronal and non-neuronal cell dynamics 2 . In vivo, all these signals vary spatially and temporally.…”