Plastic Surgery Research Council
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PREDICTABLE AND DURABLE FAT GRAFTING BY TARGETED PROTECTION OF THE DONOR MICROVASCULATURE USING PHOSPHODIESTERASE 5 INHIBITORS (PDE5I)
Presenter: Obi Ezeamuzie
Co-Authors: Ezeamuzie O; Ojo CO; Ham MJ; Lalezarzardeh F; Lotfi P; Wilson SC; Saadeh PB; Ceradini DJ
NYU Medical Center

Background: Autologous fat grafting is limited by unpredictable long-term retention of transplanted fat. We postulate that a functional donor graft microvasculature is critical for survival, and that vascular injury during harvest and the subsequent ischemic period may account for this clinical variability. Here we examine the use of the FDA-approved PDE5i sildenafil citrate to protect the donor graft microvasculature from ischemic injury, facilitating revascularization & long-term retention.

Methods: Inguinal fat from donor Tie2/LacZ FVB mice was infiltrated with sildenafil or saline 20min prior to harvest, and transplanted onto the dorsum of recipient FVB mice. Additional donors were perfused with intra-arterial trypsin to disrupt the fat graft microvasculature prior to harvest & transplantation. Graft revascularization, perfusion, volume of retention, and biochemical changes to the vasculature were assessed.

Results: Surviving fat grafts were characterized by exclusively donor-derived vasculature with peripheral inosculation to the recipient circulation. Disruption of the donor microvasculature with trypsin significantly decreased graft perfusion at 2 weeks vs. saline controls (47 FU vs. 97 FU, p<0.05) with complete graft loss by 8 weeks. Sildenafil markedly decreased ischemic injury to the donor vasculature (95% reduction in VCAM-1, 67% reduction in SDF-1 at 48hrs) and increased vascular survival at 2 weeks (400% increase in CD31 & LacZ expression) compared to saline controls (p<0.01 for all values). This improved early graft perfusion (167 FU vs. 97 FU at 2wks, p<0.05), and doubled the volume of retention at 12wks (80% vs. 40%, p<0.05) compared to saline-treated grafts.

Conclusions: Fat graft vascularization is critically dependent on maintenance of the donor fat vasculature during the ischemic period. Sildenafil protects the donor microvasculature during transfer and revascularization, markedly increasing long-term graft volume retention. These data demonstrate a rapidly-translatable, FDA-approved method to increase predictability and durability of autologous fat grafting in clinical practice.


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