Institute of Reconstructive Plastic Surgery, New York University Medical Center, 560 First Avenue, TCH-169, New York, NY 10017, USA.
J Plast Reconstr Aesthet Surg. 2012 Feb;65(2):219-27. doi: 10.1016/j.bjps.2011.08.046. Epub 2011 Oct 1.
Fat grafting has been shown clinically to improve the quality of burn scars. To date, no study has explored the mechanism of this effect. We aimed to do so by combining our murine model of fat grafting with a previously described murine model of thermal injury.
Wild-type FVB mice (n=20) were anaesthetised, shaved and depilitated. Brass rods were heated to 100°C in a hot water bath before being applied to the dorsum of the mice for 10s, yielding a full-thickness injury. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5cc of human fat/saline. Half were sacrificed 4 weeks following grafting, and half were sacrificed 8 weeks following grafting. Both groups underwent repeat Doppler scanning immediately prior to sacrifice. Burn scar samples were taken following sacrifice at both time points for protein quantification, CD31 staining and Picrosirius red staining.
Doppler scanning demonstrated significantly greater flux in fat-grafted animals than saline-grafted animals at 4 weeks (fat=305±15.77mV, saline=242±15.83mV; p=0.026). Enzyme-linked immunosorbent assay (ELISA) analysis in fat-grafted animals demonstrated significant increase in vasculogenic proteins at 4 weeks (vascular endothelial growth factor (VEGF): fat=74.3±4.39ngml(-1), saline=34.3±5.23ngml(-1); p=0.004) (stromal cell-derived factor-1 (SDF-1): fat=51.8±1.23ngml(-1), saline grafted=10.2±3.22ngml(-1); p<0.001) and significant decreases in fibrotic markers at 8 weeks (transforming growth factor-ß1(TGF-ß): saline=9.30±0.93, fat=4.63±0.38ngml(-1); p=0.002) (matrix metallopeptidase 9 (MMP9): saline=13.05±1.21ngml(-1), fat=6.83±1.39ngml(-1); p=0.010). CD31 staining demonstrated significantly up-regulated vascularity at 4 weeks in fat-grafted animals (fat=30.8±3.39 vessels per high power field (hpf), saline=20.0±0.91 vessels per high power field (hpf); p=0.029). Sirius red staining demonstrated significantly reduced scar index in fat-grafted animals at 8 weeks (fat=0.69±0.10, saline=2.03±0.53; p=0.046).
Fat grafting resulted in more rapid revascularisation at the burn site as measured by laser Doppler flow, CD31 staining and chemical markers of angiogenesis. In turn, this resulted in decreased fibrosis as measured by Sirius red staining and chemical markers.
脂肪移植已在临床上被证明可改善烧伤瘢痕的质量。迄今为止，尚无研究探讨这种效果的机制。我们旨在通过将我们的脂肪移植小鼠模型与以前描述的热损伤小鼠模型相结合来实现这一目标。
野生型 FVB 小鼠（n=20）麻醉、剃毛和脱毛。黄铜棒在热水浴中加热至 100°C，然后将其应用于小鼠背部 10 秒，产生全层损伤。在 2 周的恢复期后，小鼠接受多普勒扫描，然后用 1.5cc 人脂肪/生理盐水进行脂肪/假移植。一半在移植后 4 周处死，另一半在移植后 8 周处死。两组均在处死前立即进行重复多普勒扫描。在两个时间点处死时，从烧伤瘢痕样本中提取蛋白质进行定量、CD31 染色和苦味酸天狼猩红染色。
多普勒扫描显示，在 4 周时，脂肪移植动物的血流明显多于盐水移植动物（脂肪=305±15.77mV，盐水=242±15.83mV；p=0.026）。在脂肪移植动物中，酶联免疫吸附试验（ELISA）分析显示，在 4 周时血管生成蛋白显著增加（血管内皮生长因子（VEGF）：脂肪=74.3±4.39ngml(-1)，盐水=34.3±5.23ngml(-1)；p=0.004）（基质细胞衍生因子-1（SDF-1）：脂肪=51.8±1.23ngml(-1)，盐水=10.2±3.22ngml(-1)；p<0.001），8 周时纤维化标志物显著降低（转化生长因子-β1（TGF-ß）：盐水=9.30±0.93，脂肪=4.63±0.38ngml(-1)；p=0.002）（基质金属蛋白酶 9（MMP9）：盐水=13.05±1.21ngml(-1)，脂肪=6.83±1.39ngml(-1)；p=0.010）。CD31 染色显示，在 4 周时，脂肪移植动物的血管生成明显增加（脂肪=30.8±3.39 个高倍视野（hpf）血管，盐水=20.0±0.91 个高倍视野（hpf）血管；p=0.029）。苦味酸天狼猩红染色显示，在 8 周时，脂肪移植动物的瘢痕指数明显降低（脂肪=0.69±0.10，盐水=2.03±0.53；p=0.046）。
脂肪移植通过激光多普勒流量、CD31 染色和血管生成的化学标志物导致烧伤部位更快的再血管化。反过来，这导致纤维化减少，如苦味酸天狼猩红染色和化学标志物所示。
