Fat Grafting Promotes Neovascularization and Alleviates Fibrosis in a Murine Burn Model
Steven M. Sultan, Jason S. Barr, BA, Caroline Szpalski, MD, Parag Butala, MD, James L. Crawford, BS, Denis Knobel, MD, Edward H. Davidson, MA MBBS, Pierre B. Saadeh, MD, Stephen M. Warren, MD, Sydney R. Coleman, MD, Alexes Hazen.
NYU - IRPS, New York, NY, USA.
Cutaneous thermal injury is characterized by dermal thrombosis and, ultimately, fibrosis and scar formation. Acutely, thermal insult results in the release of endothelial progenitor cells into the bloodstream. This supply of circulating EPC’s is depleted within 72 hours, however. We hypothesize that by fat grafting beneath a burn we can deliver adipose-derived stem cells to the actively regenerating burn wound bed, allowing for improved neovascularization and decreased fibrosis.
Wild type FVB mice (n=20) were anesthetized, shaved and depilitated. Stainless steel rods were heated to 100°C in a hot water bath before being applied to the dorsum of the mice for 10 seconds. This thermal insult was determined in pilot studies to yield a reproducible full-thickness burn. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5 cc’s of human fat/saline. The first group was sacrificed at 4 weeks following grafting, while the second was sacrificed 8 weeks following grafting. Both had repeat Doppler scanning immediately prior to sacrifice. Burn tissue samples were taken following sacrifice at both time points for histologic analysis and protein quantification. CD31 staining and VEGF ELISA were performed to measure vascularity. Epidermal thickness at the burn site was measured randomly on H&E stained sections and averaged as a marker of fibrosis.
Doppler scans at 2 weeks following burn injury demonstrated a mean flux within the burn of 188.8±10.3 mV. 4 weeks following grafting, fat-grafted animals demonstrated a mean flux at the burn site of 305.4±15.7 mV, while sham-grafted animals demonstrated a mean flux of 241.8±15.8 mV (p=.01). On CD31 staining 4 weeks following grafting fat grafted animals were found to have 34.3±2.2 vessels per high-powered field in the zone surrounding the burn site, while saline treated animals had 20.3±1.3 vessels/hpf (p<.001). VEGF ELISA 4 weeks following fat/sham grafting demonstrated 47.1±3.8 pg/ml of VEGF in the scar tissue of fat grafted animals and 34.6.1±1.4 pg/ml of protein in the scar tissue of sham treated animals (p=.01). Mean epidermal thickness over the burn site was found to be 12.3±0.5 microns in fat grafted animals and 15.7±1.1 microns in sham treated animals 4 weeks following grafting (p=.02).
Fat grafting results in improved neovascularization of burn scar tissue, resulting in decreased fibrosis and better gross appearance. This study offers a scientific rationale for results observed clinically when using autologous fat grafting to improve the appearance of burn scars.
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