Effect of local, long-term delivery of platelet-derived growth factor (PDGF) on injected fat graft survival in severe combined immunodeficient (SCID) mice

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Summary

Background

Autogenous fat injection is widely used for the correction of acquired and congenital soft tissue defects. However, the high absorption rate results in the need for over-correction of the defect and repeat procedures. We hypothesised that platelet-derived growth factor (PDGF), a potent mitogen and known stimulant for murine preadipocytes, would improve fat graft survival when concentrations were sustained with a gelatine microsphere delivery system.

Methods

Abdominal fat was harvested from an otherwise healthy 43-year-old woman during a breast reconstruction. Prior to subdermal injection into severe combined immunodeficient (SCID) mice, the fat grafts were divided into 1-ml aliquots, mixed with microspheres bound to PDGF, free PDGF, or nothing depending on its experimental group, and weighed. The following experimental groups were thus created (minimum n = 8 per group): (1) fat graft control, (2) fat graft with free PDGF, (3) fat graft with blank microspheres, and (4) fat graft with microspheres bound to PDGF. After 12 weeks, the fat xenografts were harvested for analysis of weight maintenance and histological and morphometric evaluation.

Results

The addition of PDGF bound to gelatine microspheres was effective in improving xenograft weight maintenance (P = 0.018) and preservation of adipose tissue architecture (P < 0.0005) compared to controls at 3 months. The microspheres were completely absorbed at 12 weeks.

Conclusions

Sustained, local delivery of PDGF via a gelatine microsphere delivery system resulted in improved weight maintenance of the xenografts with greater preservation of adipose tissue architecture at 3 months compared to controls.

Section snippets

Animals

All experiments were performed with the prior approval of the St. Vincent's Hospital, Melbourne, Animal Ethics Committee, under the National Health and Medical Research Council Guidelines (Australia). Severe combined immune deficient (SCID) mice weighing between 20 and 25 g were used for this experiment. The SCID mouse model allows for the study of transplanted human fat without the immunological sequelae of rejection.20

Fat graft and experimental design

Fat was harvested by excision from the abdomen of an otherwise healthy

Statistical analysis

Groups were compared using one and two way analysis of variance (ANOVA) on SPSS v12.0. In the two way ANOVA, presence of spheres and addition of PDGF-BB were treated as the two independent variables. Alpha was set at 0.05.

Gross observations

There was no gross indication of acute infection, inflammation, abscess formation, seroma, or necrosis of the graft itself or the adjacent host tissue in any animal. Macroscopic observation of the fat grafts in all animals revealed consolidation of the grafted tissue into a

Discussion

Despite technical improvement in the procurement, handling, and delivery of free fat grafts, continued dissatisfaction with their survival has led to a variety of pharmaceutical interventions to improve the integrity of grafted adipocytes.14 Treatments have included insulin, steroids, vitamin E, lidocaine, epinephrine, and selective beta1 blockade.15, 16, 30, 31, 32 Although these interventions have displayed disappointing clinical efficacy, the focus on the biological behaviour of the

Acknowledgements

Dr. Randall Craft was funded by the Mayo Foundation. The authors thank Sue McKay, Liliana Pepe, and Anna Defteros for their surgical assistance.

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