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Review
. 2021 Jan 21;32(1):15.
doi: 10.1007/s10856-020-06476-5.

Regenerative medicine for skeletal muscle loss: a review of current tissue engineering approaches

Benjamin Langridge  1   2   3 , Michelle Griffin  4   5   6 , Peter E Butler  4   5   6
Affiliations
Review

Regenerative medicine for skeletal muscle loss: a review of current tissue engineering approaches

Benjamin Langridge et al. J Mater Sci Mater Med. .

Abstract

Skeletal muscle is capable of regeneration following minor damage, more significant volumetric muscle loss (VML) however results in permanent functional impairment. Current multimodal treatment methodologies yield variable functional recovery, with reconstructive surgical approaches restricted by limited donor tissue and significant donor morbidity. Tissue-engineered skeletal muscle constructs promise the potential to revolutionise the treatment of VML through the regeneration of functional skeletal muscle. Herein, we review the current status of tissue engineering approaches to VML; firstly the design of biocompatible tissue scaffolds, including recent developments with electroconductive materials. Secondly, we review the progenitor cell populations used to seed scaffolds and their relative merits. Thirdly we review in vitro methods of scaffold functional maturation including the use of three-dimensional bioprinting and bioreactors. Finally, we discuss the technical, regulatory and ethical barriers to clinical translation of this technology. Despite significant advances in areas, such as electroactive scaffolds and three-dimensional bioprinting, along with several promising in vivo studies, there remain multiple technical hurdles before translation into clinically impactful therapies can be achieved. Novel strategies for graft vascularisation, and in vitro functional maturation will be of particular importance in order to develop tissue-engineered constructs capable of significant clinical impact.

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Conflict of interest statement

The authors declare that they have no conflict of interest. This work has not previously been presented in any format. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Figures

Fig. 1
Fig. 1
Structure of skeletal muscle (Modified from Beldjilali-Labro et al. [34] under Creative Commons License)
Fig. 2
Fig. 2
Histological sample from a porcine model of VML by Greising et al. [13]. VML injury was created through surgical excision of porcine peroneus tertius muscle, with histological samples taken at 12 weeks after injury. Significant fibrosis infiltrating into native muscle is seen. Masson’s Trichrome stained sample (Connective tissue is blue; nuclei are purple; skeletal muscle fibres are red). Reproduced under Creative Commons License
Fig. 3
Fig. 3
3D bioprinting of a skeletal muscle construct with sacrificial gelatin hydrogel components to generate microchannels within the construct. These microchannels facilitate the diffusion of oxygen and nutrients to cells at the centre of the construct. (Modified from Kim et al. 2018 [117] under Creative Commons License)
Fig. 4
Fig. 4
The use of bioreactors to perfuse skeletal muscle tissue constructs improves cellular survival. This bioreactor model permits parallel incubation of multiple tissue constructs (Modified from Quarta et al. [110] under Creative Commons License)
Fig. 5
Fig. 5
Structure of muscle tendon (Modified from Beldjilali-Labro et al. [34] under Creative Commons License)
Fig. 6
Fig. 6
Histological images demonstrating aligned, newly formed myofibers in bioprinted skeletal muscle constructs at 4 and 8 weeks post implantation. (Reproduced from Kim et al. [117] under Creative Commons License)
See this image and copyright information in PMC

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