Development of a novel smart scaffold for human skeletal muscle regeneration

Abstract

Skeletal muscle defects are notoriously difficult to manage and the current methods used are associated with many limitations. Engineered skeletal muscle tissue has the potential to provide a solution that circumvents these disadvantages. Our previous work has identified a novel three-dimensionally aligned degradable phosphate glass fibre scaffold that can support myoblast differentiation and maturation. This current study has further developed the scaffold by encasing the fibres within a collagen gel to produce a smart composite scaffold that provides key biomimetic cues and supports the formation of a tissue that may be implanted in vivo. The constructs formed were approximately 30 mm long and microscopic examination confirmed favourable unidirectional cell alignment. There was good cell survival, and gene expression studies demonstrated upregulation of the myogenic regulatory factors and developmental and adult myosin heavy chain isoforms indicating myofibre formation and maturation respectively. Compared with the three-dimensional glass fibre scaffolds, the composite scaffolds had later gene upregulation, however, the use of collagen gels reinforced with degradable aligned glass fibres offers the opportunity to create a tissue analogue that can be easily manipulated. Furthermore, the glass fibre ends could support tendon/bone formation, and the channels formed as the fibres degrade could allow for vascular ingrowth.

Alignment of Skeletal Muscle Cells Cultured in Collagen Gel by Mechanical and Electrical Stimulation

“…During in vivo skeletal muscle development many factors are reported to direct the alignment of skeletal muscle cells [11][12][13][14][15][16][17][18][19][20]. Among them, mechanical stress-like tension or movement of the fetus and electrical load have been reported to exert an influence on cell alignment in vivo.…”

A novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain

“…With regard to cellular alignment, micropatterned polymer surfaces offering precise control over scaffold nano-or microtopology have been used to promote guided myotube formation [33][34][35]. In terms of muscle maturity, electric stimulation has been demonstrated to enhance the contractile force of engineered muscle in two-and three-dimensional settings [36][37][38][39].…”

3D‐Printed Biomimetic Scaffold Simulating Microfibril Muscle Structure

“…This is because it is a major component of skeletal muscle and an important biocompatibility consideration around the interactions between the Arg‐Gly‐Asp (RGD) domains and the integrin receptors in cell membrane . Recently, Shah et al fabricated an aligned phosphate‐based glass fiber scaffold, which was coated with collagen; the cultured myoblasts showed upregulated aligned myofiber formation and gene expression . Additionally, Chen et al fabricated collagen scaffolds containing microgrooves using water‐dispensing and freeze‐drying techniques.…”