Engineering skeletal muscle tissue--new perspectives in vitro and in vivo.
Bottom Line: However, the field of skeletal muscle TE has been developing tremendously and new approaches and techniques have emerged.This review will highlight recent developments in the field of nanotechnology, especially electrospun nanofibre matrices, as well as potential cell sources for muscle TE.Important developments in cardiac muscle TE and clinical studies on Duchenne muscular dystrophy (DMD) will be included to show their implications on skeletal muscle TE.
Affiliation: Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany.Show MeSH
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Mentions: Regarding the architecture, matrices can be divided into randomly orientated scaffolds and matrices with a certain alignment (Fig. 1). Commonly used matrices with random orientation, e.g. gels and sponges, can be used for a variety of tissues. However, in case of skeletal muscle this tissue naturally consists of bundles of highly oriented muscle fibres in an extracellular 3D matrix to form an organized tissue with high cell density. The parallel orientation of muscle fibres guarantees the generation of longitudinal force after contraction that is induced by motoneuron activity in vivo. Another key factor in TE is the composition of the extracellular matrix (ECM) which plays an important role in the alignment and differentiation of myoblasts [21–22]. Ideally the ECM constitutes the framework for cell adhesion and tissue growth, which includes cell proliferation and differentiation. The parallel alignment of the natural ECM in skeletal muscle tissue can be mimicked by matrix architecture. Different methods are in use to achieve parallel alignment depending on the question whether 2D or 3D matrices should be used. Regarding 2D scaffolds, alignment can be generated by electrospinning as well as microgrooving. The method of microgrooving uses either abrasives to directly grind microgrooves into the matrix as described by Shimizu et al. or generating micropatterned moulds and casting the liquid matrix material onto the mould as described by Walboomers and others [24–25]. The fabrication of micropatterned matrices has been developed for in vitro analysis of cell behaviour and differentiation on aligned surfaces and showed orientated cell growth of, e.g. fibroblasts [26–27], myoblasts  and neural cells [29–30] along the microgrooves. This phenomenon commonly termed as ‘cell guidance theory’[24, 31] encourages and facilitates myogenic differentiation in vitro. Flaibani and coworkers analysed electrical stimulation in addition to microgrooved poly-(L-lactic-acid) membranes on the differentiation of muscle precursor cells . This setting increased the myogenic differentiation of myoblasts even more than cultivation on micropatterned membranes without electrical stimuli . Though very valuable for in vitro studies analysing cell structure and differentiation, this 2D method is not suitable for engineering 3D muscle tissue. For engineering transplantable muscle tissue in vitro and for in vivo application of skeletal muscle TE a 3D approach is necessary.
Affiliation: Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany.