Adipose Tissue Engineering: Obesity Disease Model and Soft Tissue Regeneration.
Bellas, Evangelia.
2012
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Abstract: The need
for physiologically relevant sustainable adipose tissue models is crucial for
understanding tissue development and disease progression, in vitro drug and product
development as well as for in vivo soft tissue regeneration. Adipose tissue is a complex
organ whose many roles are becoming better understood. Once thought of a static organ
for energy storage, adipose tissue has ... read morenow been discovered to have more dynamic roles,
namely those in metabolism and endocrine signaling. Our understanding of its biology is
crucial on many levels. Excess adipose tissue is linked to obesity, type II diabetes,
increased cardiovascular risk and any associated co-morbidities. On the other hand, a
lack of adipose tissue also carries its own metabolic consequences. Currently, adipose
tissue biology is mainly studied in the context of monolayer in vitro cultures, or small
animal in vivo studies. Both methods offer insight to the system, yet neither
approximate the complex nature of human adipose tissue. Adipose tissue also functions as
a protective layer for our organs and maintains body contours. Soft tissue defects, most
often are the result of trauma, congenital defects, or tumor removal. These defects have
emotional and social consequences associated with the deformity and fear of not being
accepted. One treatment for filling these defects is fat grafting. However, fat
grafting, as with other fillers, does not retain volume over time, with 20-90% lost over
the first few months. Therefore, there is a large unmet clinical need for a soft tissue
filler that maintains its volume. The goal of this research is to create a
physiologically relevant adipose tissue construct to be used as an in vitro platform for
studying tissue and disease development, as well as a platform for testing potential
therapeutics. This adipose tissue construct can serve as a template for in vivo soft
tissue regeneration. In this dissertation the work centers on exploiting our knowledge
of adipose tissue engineering and silk biomaterials. Silk biomaterials can be processed
to have a range of physical, mechanical and degradation profiles. Our long-term vascular
adipose tissue construct served as a foundation for further long term studies in obesity
modeling as well as for soft tissue regeneration. The long-term vascular adipose tissue
maintained adipose-like outcomes over a 6 month period, and was improved by dynamic
culture. From this, we developed a model of diet-induced obesity by challenging this
system with free fatty acids and monocytes to generate inflammation. This model is in
line with clinical readouts and can be generated from a patient's own cells. We showed
we use therapeutics to try and reverse the inflammatory cascade of obesity. Finally, our
in vivo 18 month study was the first to show that we can maintain volume while actually
regenerating tissue when silk sponges are soaked with lipoaspirate. This model now is
being translated into injectable formats to be minimally invasive. Ongoing pre-clinical
studies are underway in a horse model for soft tissue
regeneration.
Thesis (Ph.D.)--Tufts University, 2012.
Submitted to the Dept. of Biomedical Engineering.
Advisor: David Kaplan.
Committee: Jonathan Garlick, Kacey Marra, and Lauren Black.
Keyword: Biomedical engineering.read less - ID:
- qn59qg20s
- Component ID:
- tufts:21084
- To Cite:
- TARC Citation Guide EndNote
