Biomedical Engineering Reference
In-Depth Information
(Heckman et al.
1994
). Daily application of LIPUS can stimulate mandibular bone
growth in baboon monkeys (El-Bialy et al.
2006
) and in growing human patients
with craniofacial syndrome (Hemifacial Microsomia) (El-Bialy et al.
2005
).
LIPUS application for 20 min/day was shown to enhance bone healing at bone
surgical lengthening (Distraction osteogenesis) in humans (El-Mowafi and
Mohsen
2005
). It has been suggested that the stimulatory effect of LIPUS on bone
fracture healing and new bone formation is due to the stimulation of angiogenesis
(Lu et al.
2008
; Doan et al.
1999
), enhancement of BMP expression (Suzuki et al.
2009
), and Type I and X collagen expression (Scheven et al.
2009
). Moreover,
LIPUS stimulates other bone-related and calcification genes in cell culture,
via intracellular signalling pathways affecting many osteogenesis related genes
(Zhou et al.
2008
).
3
Gene-Based Approaches for Bone Regeneration
and Associated Challenges
Employing gene-based agents, rather than bioactive proteins, is an alternative for
effective bone regeneration. Rather than mass-producing a bioactive protein by
recombinant technology, one employs the genes coding for bioactive proteins and
relies on
in situ
production of the proteins for stimulation of bone regeneration
(Fig.
1
). The most common approach for gene-based therapy involves
ex vivo
trans-
fection of cells with therapeutic genes for administration into a patient. This
approach typically requires harvesting bone marrow aspirate from a patient, and
expanding the plastic-adherent population of cells (Fig.
2a
). Although other
sources, such as adipose tissue, might be more convenient, bone marrow aspirates
are likely to provide more osteogenic cells critical for regeneration. Following
expansion, cultures are transfected, and the transformed cells purified from the
unmodified cells. The cells now expressing the desired growth factor would
be administered to the patient, allowing
in vivo
production of the growth factor by
the host's own cells. Since the host's own cells are grafted, there is no risk of
immune response and the
ex vivo
modification gives more control over the transfec-
tion procedure to ensure that cells are properly expressing the therapeutic gene.
However, this method is not without its road-blocks, particularly in translating such
technology to a clinical setting. To begin, the costs associated with a separate sur-
gery to collect marrow aspirate and subsequent cell culture required would be sig-
nificant. Several millions of cells are estimated to be required for such cell-based
therapies, meaning the original sample would have to be expanded over several
weeks. If the cell-based therapy is to be used to deal with trauma, this lengthy cul-
ture period would mean a delay in treatment, usually unacceptable in a clinical.
A lengthy expansion time may also result in changes in the desired characteristics
of the bone marrow stromal cells. Ideally, a population of mesenchymal stem cells
would be best for cell-based bone regeneration, as they have multi-lineage potential
and thus able to differentiate into chondrocytes and osteoblasts. The cells at the end
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