Biomedical Engineering Reference
In-Depth Information
scaffolds composed of mainly calcium phosphates are brittle, a material that is based
on a polyester or gel modified with different compositions of calcium phosphate
crystals would likely produce a three-dimensional, controlled structure capable of
enhancing bone regeneration.
In order to produce a scaffold that also fulfills its biological demands, introducing
mesenchymal or embryonic stem cells into tested scaffolds has been proposed. The
foundation of this strategy would be to provide the bone defect with cells capable
of either repairing the injured bone, or enhancing the ability of surrounding cells to
remodel the defect in response to local mechanical signals.
7 Stem Cell Mechanobiology
The two main characteristics of stem cells are their ability to self potentiate, and
their ability to differentiate. These characteristics are governed by what is called a
“stem cell niche,” a microenvironment in tissue where stem cells reside indefinitely
while dividing into progenitor cells [
45
-
47
]. It is thought that cells no longer in
self-renewal undergo differentiation, guided by factors within this “stem cell niche”
that dictate their fate [
45
,
47
,
48
]. The different factors and signaling molecules
involved in lineage determination has been extensively studied, but the role of me-
chanical factors in guiding stem cell fate is still unknown [
47
,
48
]. Three mecha-
nisms are believed to be involved in stem cell response to mechanical stress: direct
cell-generated forces due to changes in the cytoskeleton, cell response due to the
change in stiffness of the surrounding environment, and response due to the effect
of external mechanical forces, such as gravity or muscle contraction [
45
-
48
].
The study of mechanobiology is essential to load-bearing tissues, such as the
skeleton [
47
]. Stem cell-based regenerative strategies that aim to incorporate me-
chanical stimulation offer a controllable mechanical environment where the optimal
environment for promoting stem cell differentiation can be determined [
47
,
48
].
In terms of the musculoskeletal system, mesenchymal stem cells (MSCs) have been
the most extensively studied [
47
]. It has been speculated that undifferentiated MSCs,
which are responsible for development into bone, are responsive to mechanical stim-
ulation mediated through the extracellular matrix [
46
-
48
]. For instance, it has been
shown that increasing collagen concentration in the matrix surrounding cells results
in MSC differentiation into an osteogenic lineage [
47
,
49
].
Despite the promising research in MSCs, the ability of embryonic stem (ES) cells
to divide indefinitely and differentiate into multiple tissue types make them equally
attractive alternatives in modern tissue engineering [
46
,
47
,
49
]. Recent studies have
shown that mechanical strain inhibits the differentiation of human ES cells while
promoting self-renewal, as well as induces the production and diffusion of calcium
and nitric oxide [
47
,
48
]. Interestingly, these stem cells, cultured while being cycli-
cally strained, retained pluripotency [
47
,
48
]. This response to mechanical load-
ing was hypothesized to involve the TGF-
β
signaling pathway, as the mechanical
stimulus resulted in upregulation of TGF-
β
[
48
]. Thus, the influence of mechanical
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