Abstract
Recently, skeletal muscle represents a complex and challenging tissue to be generated in vitro for tissue engineering purposes. Several attempts have been pursued to develop hydrogels with different formulations resembling in vitro the characteristics of skeletal muscle tissue in vivo. This review article describes how different types of cell-laden hydrogels recapitulate the multiple interactions occurring between extracellular matrix (ECM) and muscle cells. A special attention is focused on the biochemical cues that affect myocytes morphology, adhesion, proliferation, and phenotype maintenance, underlining the importance of topographical cues exerted on the hydrogels to guide cellular orientation and facilitate myogenic differentiation and maturation. Moreover, we highlight the crucial role of 3D printing and bioreactors as useful platforms to finely control spatial deposition of cells into ECM based hydrogels and provide the skeletal muscle native-like tissue microenvironment, respectively.
Highlights
Skeletal muscle (SKM) represents a tremendously complicated tissue to generate in vitro due to the complex and finely controlled interconnections occurring between its components, which form a mature tissue able to exert its contractile function
Muscle extracellular matrix (ECM) houses a number of peptides and cell types such as macrophages, fibroblasts, and the muscle-specific stem cells that reside in a quiescent state in a well-defined anatomic location, representing their niche [5,6]
SKM formation is guaranteed from embryogenesis to adult life and a key role is played by several growth factors able to modulate multiple processes occurring in SKM tissue, such as maintaining the quiescence of SCs or modulating ECM-cells interactions
Summary
Skeletal muscle (SKM) represents a tremendously complicated tissue to generate in vitro due to the complex and finely controlled interconnections occurring between its components, which form a mature tissue able to exert its contractile function. For this reason, we summarized the most recent exploited approaches to induce different topographical characteristics to hydrogels, giving strength to the concept that a SKM-like scaffold should resemble the correct cell-ECM interactions but may possess structural and biomechanical properties as similar as possible to the native SKM tissue. We summarized the most recent exploited approaches to induce different topographical characteristics to hydrogels, giving strength to the concept that a SKM-like scaffold should resemble the correct cell-ECM interactions but may possess structural and biomechanical properties as similar as possible to the native SKM tissue In this context, a finely controlled spatial cell deposition into the 3D scaffolds acquires peculiar importance in developing a SKM-like tissue. It is mandatory to highlight the importance of SKM devices, namely bioreactors, to guide and monitor the maturation of such engineered muscle tissues [8]
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