Efficacy and mechanisms of vacuum-assisted closure (VAC) therapy in promoting wound healing: a rodent model.

BACKGROUND: The vacuum-assisted closure device (VAC) has revolutionised wound care, although molecular mechanisms are not well understood. We hypothesise that the VAC device induces production of pro-angiogenic factors and promotes formation of granulation tissue and healing. METHODS: A novel rodent model of VAC wound healing was established. Excisional wounds were created on rat dorsa. Wounds were dressed with Tegaderm (control group), VAC Granulofoam and Tegaderm (special control group), or VAC Granulofoam, T.R.A.C. PAD((R)) with 125 mm Hg continuous negative pressure (VAC group). Wound closure rates were calculated as a percentage of initial wound sizes. Rats were sacrificed on postoperative days 3, 5 and 7; harvested tissues were processed for histology [haematoxylin & eosin (H&E), Masson's trichrome, picrosirius red] and Western blot analysis (CD31, vascular endothelial growth factor, basic fibroblast growth factor). RESULTS: Statistically significant wound closure rates were achieved in the experimental group at all measured time points: day 3, 28.1% (VAC) vs 8.2% (control) and 8.8% (special control) (ANOVA, P<0.0001); day 5, 45.3% (VAC) vs 23.7% (control) and 22.5% (special control) (ANOVA, P=0.0003); day 7, 54.4% (VAC) vs 43.0% (control) and 31.5% (special control) (ANOVA; P<0.0001). Morphological evaluation by Masson's trichrome stain showed increased collagen organisation and wound maturation in the VAC group. These wounds also showed increased expression of vascular endothelial growth factor and fibroblast growth factor-2 on day 5 by Western blot analysis. CONCLUSION: A small animal VAC wound model was established. Wounds treated with a VAC device showed accelerated wound closure rates, increased pro-angiogenic growth factor production and improved collagen deposition. Further application of this model may elucidate other mechanisms.

Wound closure and metabolic parameter variability in a db/db mouse model for diabetic ulcers.

BACKGROUND: Diabetic foot ulcers are a major cause of nontraumatic lower extremity amputations. Wound-healing researchers commonly use db/db mice as a model for diabetes, while the excisional wound correlates well with chronic foot ulcers. Recent clinical trials identified a correlation between glycemic control and cardiovascular complications in diabetic patients. The purpose of this study was to determine if the severity of diabetes was related to poor wound healing and the broad wound closure variability observed in diabetic db/db mice. MATERIALS AND METHODS: Adult female C57BLKS/J, db+/-, and db/db mice were anesthetized followed by creation of a 1.5 x 1.5 cm full-thickness excisional wound. Wound closure was measured on postoperative days (PODs) 1, 5, 7, 10, 14, and 21. Weight, fasting blood glucose, and fasting insulin were also measured during the study. RESULTS: By POD 21 both wild-type and db+/- mice demonstrated complete wound closure. In db/db mice open wounds were still present at POD 21. There was a broad range of percent wound closure from 24 to 81% with a mean of 55%. Despite strong correlations between diabetic parameters, there was no significant correlation between wound closure rate and severity of diabetes. CONCLUSIONS: Diabetic db/db mice exhibit a significant impairment of healing in the excisional wound model. The variability of wound closure for individual mice did not correlate with severity of obesity, hyperglycemia, hyperinsulinemia, or insulin resistance. An extensive evaluation of basic diabetes parameters does not provide significant insight into the wound-healing process in the db/db mouse model.