DESIGNING NANOFIBROUS SCAFFOLDS FOR TISSUE ENGINEERING - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 467

13.5.2.3.1 POTENTIAL CELL SOURCES FOR SKELETAL MUSCLE TISSUE
ENGINEERING. The diseases caused due to skeletal muscle injury have led to a
considerable interest in skeletal muscle regeneration. During skeletal muscle
regeneration, myoblasts undergo proliferation, differentiation, and fusion to form
a multinucleated structure typical of muscle myofi bril. These myofi brils then
undergo a specifi c arrangement to form a functional muscle. High degree of func-
tional and structural specialization in the adult skeletal tissue results in existence
of terminally-differentiated cell populations that have lost the capacity to prolif-
erate and to form new myofi brils during tissue repair. Thus, cell replenishment is
attributed to a store house of undifferentiated cells, called satellite cells, present
in close contact with the myofi brils [258]. Under normal conditions, the satellite
cells remain quiescent and can be activated through signals that are secreted fol-
lowing cell damage. Satellite cells are termed as precursor cells, rather than stem
cells, due to their ability to produce only a single lineage of cells unlike multipo-
tent stem cells. However, the use of satellite cells in skeletal tissue repair has been
limited due to the non-availability of a pure populations of these cells. Montarras
et al. isolated satellite cells by fl ow cytometry using satellite cell specifi c markers.
These cells, when grafted into muscles of nude mice that lacked dystrophin (a
protein mutated in patients having Duchenne muscular dystrophy), led to fi ber
repair [259]. Satellite cells are the most characterized of all the muscle-derived
stem cells (MDSCs). MDSCs exhibit varied degrees of pluripotency and can dif-
ferentiate into osteogenic lineage, adipogenic lineage, chondrogenic lineage, or
skeletal myogenic lineage, depending on the culture conditions [260]. Further,
experimental studies have validated the potential use of myoblasts in muscle
tissue engineering [261].
13.5.2.3.2 SCAFFOLD FOR SKELETAL MUSCLE TISSUE ENGINEERING. Appropri-
ate functioning of tissue-engineered skeletal muscle requires the proper organi-
zation of myofi brils, intracellular calcium storage, and acetyl-choline receptors
that are important for the functioning of the muscle. The orientation of muscle
cells should be in a direction parallel to each other in order to produce force in a
desired direction. Thus, the scaffold should allow/facilitate the orientation of
muscle cells in a parallel fashion. In addition, the scaffold should be biocompati-
ble, moldable to provide suffi cient strength, and must possess a vascular compo-
nent [262]. Levenberg et al. reported the vascularisation of engineered skeletal
muscle tissue constructs using a three-dimensional multiculture system consisting
of myoblasts, fi broblasts, and endothelial cells on biodegradable PLLA/PLGA
scaffolds [263]. Their results demonstrated the presence of endothelial vessel
network throughout the engineered muscle tissue in vitro and improved perfor-
mance of the constructs in vivo (in a mouse model) following pre-vascularisation.
In previous tissue-engineering strategies, myoblasts have been seeded on
fi brous meshes [264], gels [265], and in between artifi cial tendons [266] with
limited success. Myoblasts seeded on fi brous meshes were unable to align them-
selves in parallel orientation, while those seeded on gels did not produce forces
comparable to those of a normal human body. Therefore, to overcome this