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5. Challenges and Outlook
Although exciting progress is being made in this field, there are still a
number of challenges that will need to be addressed. These include
the complexity of the muscle’s natural structure, which contains many
cell types and is organized into a very specific structure.^75 Although it
has been shown that use of multiple cell types can be beneficial in
forming vascularized tissue, very little work has been done on inner-
vating the tissue in vitro.^75 Another problem, which is more specific
to VML, is the use of fresh wound models.^76 These wounds do not
really reflect what happens in clinical practice, where it is more likely
that the body will have already gone through some of the healing and
remodeling process before a tissue engineered intervention is intro-
duced.11,77 To move forward, it will be necessary to begin integrating
knowledge about the primary cell types in skeletal muscle. Although
the three cell types discussed here have very different roles and struc-
tures, it is clear that they all have the potential to respond to the same
mechanobiological stimuli. It is hoped that this work will serve as a
tool for future tissue engineering endeavors as more biologically rel-
evant muscle constructs continue to be developed. Questions yet to
be answered include, details such as whether cyclic or static strain are
able to provide better results for myoblast proliferation or differentia-
tion. Also, what is the best way to reconcile the differences in the
electrical stimulation methods used by researchers? All of these chal-
lenges will need to be addressed for the field to move forward to a
point where skeletal muscle tissue engineering for VML is clinically
useful.
References
- Ehmsen J, Poon E, Davies K. The dystrophin-associated protein
complex. J. Cell Sci. 115 (14), 2801–2803 (2002). - Godfr ey C, Muses S, McClorey G, Wells KE, Coursindel T, Terry RL,
Betts C, Hammond S, O’Donovan L, Hildyard J, El Andaloussi S, Gait
MJ, Wood MJ, Wells DJ. How much dystrophin is enough: the physi-
ological consequences of different levels of dystrophin in the mdx
mouse. Hum. Mol. Ge. 24 (15), 4225–4237 (2015).
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