Tissue Engineering And Nanotheranostics

“9.61x6.69” b2815 Tissue Engineering and Nanotheranostics

Engineering Approaches for Creating Skeletal Muscle 13

of collagen was used as a scaffold, and differentiated EMSCs were

allowed to grow to form a cell sheet, eventually degrading the original

collagen scaffold.^52 Following 14 days of culture, the cell sheet morphol-

ogy was generally aligned, and composed of elongated cells.^52 The cell

sheets were rolled to form a 3D structure, then implanted into an excised

volume muscle defect model in the quadriceps of BALB/C mice.^52 The

allograft was allowed to grow for 14 days, then removed for analysis.^52 It

was found that MyoD, an important myogenic marker, was detected in

the excised construct.^52 Furthermore, it was found the EMSCs fused and

formed multinucleated cells.^52 Another study done on SCs in vitro to

form 3D constructs through spontaneous detachment and 3D organiza-

tion found that it was possible to make cylindrical muscle constructs that

were contractile under electrical stimulation.^49 Most recently, the emerg-

ing technique of 3D bioprinting was used to print mouse myoblasts into

tube structures.^53 Many of these approaches may prove to be useful in the

future of tissue engineered muscle.

4.2.1. Vascularization

Transport of gasses, nutrients, and waste are critical to any tissue.

Consequences due to the lack of functional vasculature become much

more apparent when tissue engineered constructs have a thickness

greater than about 200 mm.^54 The diffusion limit of oxygen is one of

the primary constraints when engineering volumetric muscle tissue,

and must be addressed if the tissue is to avoid necrosis.^54 In skeletal

muscle engineering, some promising approaches take a multicellular

approach to the problem of forming capillary beds ex vivo. In one

approach, wild-type mouse muscle was broken up and the cells were

obtained by dissociation from the matrix.^55 The resulting cells were

cultured in a dish to form a cell sheet, which was then immobilized at

two opposing points to allow the cell sheet to spontaneously roll into

a 3D spindle.^55 It was found that not only did the cells form myofib-

ers, but also the endothelial cells in the culture organized into vascu-

lar-like structures.^55 When implanted into an injury model in the

tibialis anterior of mice, the engineered muscle could integrate with

the native tissue and it was shown to have a significant effect on the

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