Biomedical Engineering Reference
In-Depth Information
Over recent years, considerable progress has been made in the design and fabrication of
novel nanofibrous scaffolds that mimic a nanoscaled ECM of native tissues. In addition, stem
cells have emerged as appropriate cellular candidates for use in tissue engineering because of
their extensive self-renewal capacity and multilineage differentiation potential. Application of
nanoscale scaffolds in combination with stem cells creates tremendous promise for promoting
regeneration in many difficult-to-treat tissue defects, including defects of the musculoskeletal
system. In the following, we will introduce the existent nanostructure in musculoskeletal tissue,
followed by a brief discussion regarding stem cells that are appropriate for cell-based treatment
of large musculoskeletal tissue defects. Finally, application of nanoengineering for each
individual tissue that comprises the musculoskeletal system will be discussed, with examples
taken from relevant literature.
Nanostructures in Normal Musculoskeletal Tissues
The body's movement is dependent on the coordinated activities of bones, cartilage, ligaments,
tendons, and muscles, all of which comprise the body's musculoskeletal system. These tissues
are developmentally produced by precursor cells referred to as mesenchymal stem cells
(MSCs). Structurally, musculoskeletal tissues consist of an ECM and cells. The ECM in turn
is comprised of a highly organized framework of organic nanofibers in an amorphous ground
substance that consists of water, proteoglycans, and noncollagenous proteins [18]. Although
individual tissues of the musculoskeletal system differ from each other in terms of biology,
structural components, and mechanical properties, interestingly, all share a network of collag-
enous fibers of approximately 100 nm in dimension in their ECM (Figure 17.2).
Bone ECM is comprised of an organic matrix of predominantly 80-160 nm collagen I nano-
fibers and mineralized matrix of approximately 20 nm nanohydroxyapatite (HA) crystals. In
bone, the concentric alignment of collagen fibers along with HA crystals is responsible for the
characteristic hardness and compressive strength of the tissue [19]. Tendons are a specific
connective tissue composed mainly of collagen nanofibers. Collagen I constitutes approxi-
mately 95% of the total tendon collagen. The remaining 5% is mainly comprised of collagens
III and V with collagens II, VI, IX, and XI present in trace quantities. Organization of the
ECM molecules at the micrometer and nanometer levels is the principal determinant of a
tendon's mechanical strength and function [20]. In articular cartilage, collagen II nanofibers of
approximately 80 nm possess a variable alignment related to chondrocytes. In the superficial
zone, collagen nanofibers are parallel to the cartilage surface, whereas in the middle and deep
zones they align perpendicular to the surface [21]. In muscular tissue each individual muscle
fiber is surrounded by a delicate layer of reticular (collagen III) fibers referred to as the
endomysium. In addition, a group of muscle fibers called the bundle or fascicle is sur-
rounded by a thicker connective tissue known as the perimysium. The epimysium is a sheath
of dense connective tissue that surrounds a collection of bundles that form the muscle [22].
Stem Cells for Musculoskeletal Tissue Nanoengineering
Stem cells are promising cellular candidates in the field of tissue engineering and regenerative
medicine because of their extensive self-renewal property and multilineage differentiation
capacity. To date, several stem-cell types have been introduced for regeneration of musculoskel-
etal tissue defects. Of these, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs),
and MSCs have gained extensive attention (Table 17.1). The ESCs are pluripotent cells derived
from a blastocyst inner cell mass. These cells possess indefinite self-renewal potential as well as
