Date of Award

January 2015

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Deepak Narayan

Subject Area(s)

Medicine

Abstract

Autologous fat grafting is the movement of fat from one region of the body to another to fill soft tissue deformities, but is limited by its unpredictable retention rates and slow revascularization. Consequently, it is only used in smaller quantities to correct minor deformities of the body. As more and more women choose post-mastectomy breast reconstruction, however, fat grafting provides an attractive autologous approach with minimal morbidity and wider availability than current techniques. Pioglitazone is an FDA-approved PPAR-γ agonist known to induce adipogenesis while pericytes are adipogenic cells that stabilize and promote the formation of new blood vessels. Therefore, we tested whether pioglitazone could drive adipogenesis in placenta-derived pericytes with the goal of using this as a platform for tissue engineering adipose tissue or augmenting current fat grafting techniques. To further promote angiogenesis of the fat graft, we evaluated the effects of post-operative hyperbaric oxygen therapy (HBOT) on fat graft survival and perfusion in vivo using μCT and SPECT imaging. HBOT has a successful history as a treatment for chronic and diabetic wounds where it has been shown to dramatically improve perfusion, mobilize stem cells from the bone marrow, and impart cytoprotective effects/ischemic tolerance in a variety of cells that are critical to angiogenesis and wound healing. Five days of post-operative HBOT noticeably improved graft perfusion at 3 weeks, but not 6 weeks and did not significantly improve volume retention over time compared to controls. Nevertheless, HBOT shows considerable promise as a non-invasive modality that could improve long-term fat graft survival by improving perfusion to the graft. Moreover, it could be combined with evolving adipose tissue engineering approaches that are designed to improve adipogenesis and angiogenesis. Due to the lack of standardized fat grafting procedures, validated parameters of success, and a paucity of high-quality comparative clinical studies, fat grafting remains an art dependent upon surgeon technique and experience rather than sound scientific evidence.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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