Fat grafting accelerates revascularisation and decreases fibrosis following thermal injury

Steven M. Sultan, Jason S. Barr, Parag Butala, Edward H. Davidson, Andrew L. Weinstein, Denis Knobel, Pierre B. Saadeh, Stephen M. Warren, Sydney R. Coleman, Alexes Hazen

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Background: 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. Methods: 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 10 s, yielding a full-thickness injury. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5 cc 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. Results: Doppler scanning demonstrated significantly greater flux in fat-grafted animals than saline-grafted animals at 4 weeks (fat = 305 ± 15.77 mV, saline = 242 ± 15.83 mV; 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 ± 4.39 ng ml -1, saline = 34.3 ± 5.23 ng ml -1; p = 0.004) (stromal cell-derived factor-1 (SDF-1): fat = 51.8 ± 1.23 ng ml -1, saline grafted = 10.2 ± 3.22 ng ml -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 ± 0.38 ng ml -1; p = 0.002) (matrix metallopeptidase 9 (MMP9): saline = 13.05 ± 1.21 ng ml -1, fat = 6.83 ± 1.39 ng ml -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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)219-227
Number of pages9
JournalJournal of Plastic, Reconstructive and Aesthetic Surgery
Volume65
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Fingerprint

Fibrosis
Hot Temperature
Fats
Wounds and Injuries
Staining and Labeling
Cicatrix
Chemokine CXCL12
Transforming Growth Factors
Metalloproteases
Baths
Vascular Endothelial Growth Factor A
Proteins
Lasers
Enzyme-Linked Immunosorbent Assay

Keywords

  • Burn
  • Fat graft
  • Stem cell

ASJC Scopus subject areas

  • Surgery

Cite this

Fat grafting accelerates revascularisation and decreases fibrosis following thermal injury. / Sultan, Steven M.; Barr, Jason S.; Butala, Parag; Davidson, Edward H.; Weinstein, Andrew L.; Knobel, Denis; Saadeh, Pierre B.; Warren, Stephen M.; Coleman, Sydney R.; Hazen, Alexes.

In: Journal of Plastic, Reconstructive and Aesthetic Surgery, Vol. 65, No. 2, 01.02.2012, p. 219-227.

Research output: Contribution to journalArticle

Sultan, SM, Barr, JS, Butala, P, Davidson, EH, Weinstein, AL, Knobel, D, Saadeh, PB, Warren, SM, Coleman, SR & Hazen, A 2012, 'Fat grafting accelerates revascularisation and decreases fibrosis following thermal injury', Journal of Plastic, Reconstructive and Aesthetic Surgery, vol. 65, no. 2, pp. 219-227. https://doi.org/10.1016/j.bjps.2011.08.046
Sultan, Steven M. ; Barr, Jason S. ; Butala, Parag ; Davidson, Edward H. ; Weinstein, Andrew L. ; Knobel, Denis ; Saadeh, Pierre B. ; Warren, Stephen M. ; Coleman, Sydney R. ; Hazen, Alexes. / Fat grafting accelerates revascularisation and decreases fibrosis following thermal injury. In: Journal of Plastic, Reconstructive and Aesthetic Surgery. 2012 ; Vol. 65, No. 2. pp. 219-227.
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abstract = "Background: 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. Methods: 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 10 s, yielding a full-thickness injury. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5 cc 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. Results: Doppler scanning demonstrated significantly greater flux in fat-grafted animals than saline-grafted animals at 4 weeks (fat = 305 ± 15.77 mV, saline = 242 ± 15.83 mV; 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 ± 4.39 ng ml -1, saline = 34.3 ± 5.23 ng ml -1; p = 0.004) (stromal cell-derived factor-1 (SDF-1): fat = 51.8 ± 1.23 ng ml -1, saline grafted = 10.2 ± 3.22 ng ml -1; p < 0.001) and significant decreases in fibrotic markers at 8 weeks (transforming growth factor-{\ss}1(TGF-{\ss}) : saline = 9.30 ± 0.93, fat = 4.63 ± 0.38 ng ml -1; p = 0.002) (matrix metallopeptidase 9 (MMP9): saline = 13.05 ± 1.21 ng ml -1, fat = 6.83 ± 1.39 ng ml -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). Conclusions: 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.",
keywords = "Burn, Fat graft, Stem cell",
author = "Sultan, {Steven M.} and Barr, {Jason S.} and Parag Butala and Davidson, {Edward H.} and Weinstein, {Andrew L.} and Denis Knobel and Saadeh, {Pierre B.} and Warren, {Stephen M.} and Coleman, {Sydney R.} and Alexes Hazen",
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T1 - Fat grafting accelerates revascularisation and decreases fibrosis following thermal injury

AU - Sultan, Steven M.

AU - Barr, Jason S.

AU - Butala, Parag

AU - Davidson, Edward H.

AU - Weinstein, Andrew L.

AU - Knobel, Denis

AU - Saadeh, Pierre B.

AU - Warren, Stephen M.

AU - Coleman, Sydney R.

AU - Hazen, Alexes

PY - 2012/2/1

Y1 - 2012/2/1

N2 - Background: 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. Methods: 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 10 s, yielding a full-thickness injury. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5 cc 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. Results: Doppler scanning demonstrated significantly greater flux in fat-grafted animals than saline-grafted animals at 4 weeks (fat = 305 ± 15.77 mV, saline = 242 ± 15.83 mV; 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 ± 4.39 ng ml -1, saline = 34.3 ± 5.23 ng ml -1; p = 0.004) (stromal cell-derived factor-1 (SDF-1): fat = 51.8 ± 1.23 ng ml -1, saline grafted = 10.2 ± 3.22 ng ml -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 ± 0.38 ng ml -1; p = 0.002) (matrix metallopeptidase 9 (MMP9): saline = 13.05 ± 1.21 ng ml -1, fat = 6.83 ± 1.39 ng ml -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). Conclusions: 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.

AB - Background: 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. Methods: 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 10 s, yielding a full-thickness injury. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5 cc 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. Results: Doppler scanning demonstrated significantly greater flux in fat-grafted animals than saline-grafted animals at 4 weeks (fat = 305 ± 15.77 mV, saline = 242 ± 15.83 mV; 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 ± 4.39 ng ml -1, saline = 34.3 ± 5.23 ng ml -1; p = 0.004) (stromal cell-derived factor-1 (SDF-1): fat = 51.8 ± 1.23 ng ml -1, saline grafted = 10.2 ± 3.22 ng ml -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 ± 0.38 ng ml -1; p = 0.002) (matrix metallopeptidase 9 (MMP9): saline = 13.05 ± 1.21 ng ml -1, fat = 6.83 ± 1.39 ng ml -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). Conclusions: 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.

KW - Burn

KW - Fat graft

KW - Stem cell

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