Biomedical Engineering Reference
In-Depth Information
It has been reported that rat condylar growth can be significantly increased by local gene ther-
apy with recombinant adenovirus associated virus (rAAV)-mediated vascular endothelial growth
factor (VEGF), which is an important angiogenic mediator in vascularization and endochondral
ossification [10] . Although rAAV vector for gene delivery is proven to be a strong and effective
vector, its use in human patients is facing controversial and ethical issues. There is a growing
emphasis on nanotechnology in cancer detection and treatment ( http://nano.cancer.gov ) . For exam-
ple, nanovector liposomes have been used successfully in breast cancer therapy [11] . Regardless of
its successful use, nanobiotechnology is still at its early stage of development and its use in treat-
ment of diseases other than cancer could be especially challenging. The challenges facing these
nanovectors might not have viable applications, especially in mandibular growth stimulation and
could end up on the “technology shelf” in the future [12] .
12.4 Nanofabricated ultrasound device for orthodontics
In translational research, proof of concept is usually the first step in testing the viability of new
technology for potential treatment of any disease. We and other researchers have shown in proof of
principle the efficacy of utilizing Low Intensity Pulsed Ultrasound (LIPUS) in stimulating mandib-
ular growth in growing animals and in human patients [13
16] . One of the main challenges we
faced when a pilot clinical trial was conducted to stimulate mandibular growth in humans with
hemifacial microsomia was that the patients (young adults) needed to hold the LIPUS transducers
(applicators) to their mandibular condyles for 20 min every day for at least 1 year in order to
achieve clinical improvement of the deficient side of the mandible. This created a great challenge
and burden on the parents to do this for that extended period of time. In order to minimize errors in
LIPUS application and maximize consistency in treatment, a noncompliant LIPUS application is in
high demand. In addition, we have shown that LIPUS application to orthodontically moving teeth
can minimize root resorption [17] . External apical root resorption (EARR) concurrent with ortho-
dontic treatment is widely accepted as a risk in all types of orthodontic treatment appliances.
Challenges in using LIPUS intraorally in treatment of EARR concurrent with orthodontic treatment
is that the size of commercially available LIPUS transducers are quite large (3.5 cm 3 ), difficult to
adjust, and larger than any human tooth. In addition, the patients have to hold the LIPUS transdu-
cers tightly against the gingiva of the corresponding tooth/teeth for 20 min/day for at least 4 weeks
in order to achieve clinically noticeable decrease in EARR concurrent with orthodontic treatment.
Because of these challenges there are needs for noncompliant LIPUS devices that can be inserted
into the patient's mouth and deliver the predesigned LIPUS treatment to the tooth/teeth in question.
In order to build an intraoral LIPUS device that is independent of power supply or patient compli-
ance, a nanocircuit design has been incorporated in order to nanofabricate the main operation
circuit as well as LIPUS transducer controller. In addition, a nanofabricated battery is required in a
nanoscale intraoral LIPUS device. The first step in this nanodesigned LIPUS device was the nano-
fabrication of the operation circuit that delivers the required signal to the LIPUS transducer. This
step has been developed by our group and tested for its validity to be potentially used for future
nanofabricated LIPUS transducers and devices [18] . A future nanofabricated LIPUS device is com-
pared to the original large-scaled device in the following figure ( Figure 12.3 ).
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