Biomedical Engineering Reference
In-Depth Information
for injuries affecting the entire joint since there would be no functional tissue to anchor the new
constructs in. As yet, there are no successful approaches to treating OA using conventional tissue
engineering. Researchers are continually investigating alternative approaches, such as engineering
a replacement tissue that can completely resurface the joint [
292
]. Other possibilities include gene
therapy or pharmaceuticals, which might have more success in treating systemic degeneration of
articular cartilage.
Cartilage growth and development are affected by both biological and biomechanical stimuli.
On the mechanical side, loading is a required part of the normal joint environment. As seen in
previous sections, while excessive forces can damage cartilage tissue, some stimulation is necessary
to promote chondrogenesis [
4
]. Articular cartilage will atrophy in a mechanically static environ-
ment [
293
], so researchers are currently evaluating a variety of loading approaches to prevent this
while promoting the regeneration process. An important factor to consider prior to mechanical load-
ing is the choice of scaffold used for the engineered construct. The scaffold material not only affects
how cells sense mechanical loads, but also provides an environment that can influence cell attachment
and matrix synthesis. In addition to mechanical stimuli, articular cartilage responds dramatically to
growth factors that are naturally present in the joint environment. The TGF-
β
superfamily includes
growth factors that are present in developing bone and cartilage. These molecules play an integral
role in the natural development process, and
in vitro
, can induce dramatic effects on the growth of
orthopaedic tissues. This section will illustrate the importance of the
in vitro
culture environment on
the growth, development, and functionality of native and engineered articular cartilage. Following
the accepted paradigm for functional tissue engineering, four main categories will be reviewed: cell
sources, biomaterials, bioactive molecules, and bioreactors [
294
].
3.2 CELL SOURCE
Cells are one of the key components of tissue engineering. While an exogenous cell source is not
absolutely necessary, studies have shown that including cells in an engineered construct accelerates
regeneration
in vitro
and
in vivo
[
295
]. Furthermore, these implanted cells have been shown to
remain in the tissue without being replaced by host cells [
295
]. Researchers have several options
when choosing a cell source. The cell type most commonly used in early cartilage engineering studies
is the autologous chondrocyte. By extracting cells from the patient's own body, any immune response
is minimized or totally removed. Furthermore, chondrocytes already are differentiated into the target
phenotype and have the capacity to secrete cartilage-appropriate matrix molecules.
The choice of cell type often depends on the initial condition of the cartilage tissue. In cases
of extensive degradation or disease, use of autologous chondrocytes is not an option. One possible
alternative is to use allogeneic chondrocytes from donor tissue. This approach is commonly used for
general
in vitro
experiments and some
in vivo
studies due to the ready availability of donor tissue.
While the cell phenotype is appropriate for the implant environment, problems can arise with respect
to tissue availability for humans, as well as possible disease transmission or immune response.
