3D Printing Skeletal Muscle

The skeletal muscle is the most abundant tissue in the body and constitutes approximately 40% of the total body mass in humans. It has a high regenerative potential after injury or illness, however, once a large amount of muscle is damaged, the endogenous self-regeneration is severely impaired. Severe traumas that result in volumetric muscle loss lead to the formation of non-functional fibrous tissue and degeneration of the intermuscular adipose tissue [1, 2].


Currently, clinical treatments include the grafting of autologous local muscle flaps. Still, this type of treatment has some disadvantages: limiting the number of adequate muscle flaps, the morbidity of the donor area, and the need for extensive physical rehabilitation. Consequently, the tissue engineering approach is promising to solve this issue [2]. This type of approach seeks to develop complex muscle structures in vitro so that it is possible to implant and replace damaged muscles and increase the formation of new muscles from the remaining tissue in vivo [3].



Figure 1: An overview of bioengineering approaches for skeletal muscle tissue engineering [2].


Stem cells present in the skeletal muscle are known as satellite cells. These cells are indispensable for the regeneration of skeletal muscle as they provide myoblasts for muscle growth [4,5]. Therefore, the satellite cells are a good source for muscle regeneration but, in contrast, they are highly heterogeneous in function, which leads to a varied efficiency in regeneration. The difficulty of isolating and purifying the cells and the low capacity for ex vivo expansion are also problems related to satellite cells that need to be addressed [6].


In 2018, Kim et al. developed a 3D bioprinting strategy to manufacture an implantable skeletal muscle for functional muscle regeneration. This bioprinted muscle construct was composed of human primary muscle progenitor cells (hMPCs) and was successfully implanted in the defect of the anterior tibial muscle of rats. Eight weeks after the implantation, the in vivo study revealed that the constructs achieved 82% functional recovery in the rodent model. This technique demonstrated the potential of using 3D bioprinted skeletal muscle with a spatially organized structure that can reconstruct extensive muscle defects [7].



Figure 2: The technique used for bioprinting skeletal muscle [7].





REFERENCES


1. Dunn, A. et al. Biomaterial and stem cell-based strategies for skeletal muscle regeneration. J. Orthop. Res. 37, 1246–1262 (2019).

2. Nakayama, K. H., Shayan, M. & Huang, N. F. Engineering Biomimetic Materials for Skeletal Muscle Repair and Regeneration. Adv. Healthc. Mater. 8, e1801168 (2019).

3. Liu, J. et al. Current Methods for Skeletal Muscle Tissue Repair and Regeneration. Biomed Res. Int. 2018, 1984879 (2018).

4. Schmidt, M., Schüler, S. C., Hüttner, S. S., von Eyss, B. & von Maltzahn, J. Adult stem cells at work: regenerating skeletal muscle. Cell. Mol. Life Sci. 76, 2559–2570 (2019).

5. Relaix, F. & Zammit, P. S. Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage. Development 139, 2845–2856 (2012).

6. Zhuang, P., An, J., Chua, C. K. & Tan, L. P. Bioprinting of 3D in vitro skeletal muscle models: A review. Mater. Des. 193, 108794 (2020).

7. Kim, J. H. et al. 3D Bioprinted Human Skeletal Muscle Constructs for Muscle Function Restoration. Sci. Rep. 8, 12307 (2018).


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