BACKGROUND: Infected wounds present a major complication in patients with diabetes. Staphylococcus aureus is the most common single isolate in diabetic wounds. Human beta-defensin (hBD)-3 is antimicrobial active and appears to play a key role in the immune response. The present study aimed to analyse the effect of hBD-3 expression in a model of infected diabetic wounds. METHODS: Excisional wounds were created on the backs of Yorkshire pigs and Ad5-CMV-hBD-3 vectors were microseeded. Wounds were inoculated with S. aureus, covered with a polyurethane chamber and analysed for transgene expression, bacterial infection, re-epithelialization, wound contraction, wound fluid production and blood vessel formation. RESULTS: hBD-3-treated wounds showed a total bacterial load of 2.1 x 10(8) colony-forming units (CFU)/g tissue, versus 1.3 x 10(9) CFU/g tissue for controls (p < 0.001) at day 4. At day 12, no statistical difference could be detected. Re-epithelialization showed 75 +/- 15% wound closure for hBD-3 expressing wounds and 50 +/- 16% for controls (p < 0.01). hBD-3 expression was in the range 15-20 ng/ml of wound fluid during day 1-4. The lower dose of 2 x 10(9) Ad5-CMV-hBD-3 showed no effect, suggesting a dose dependency for hBD-3. CONCLUSIONS: In the present study, we show that hBD-3 expression significantly promotes wound closure in S. aureus infected diabetic wounds in a preclinical large-animal model. Furthermore, a ten-fold reduction of bacterial growth on day 4 was detected. These findings indicate that beta-defensin-3 may play a major role in diabetic wound healing and wound infections.
BACKGROUND: Infected wounds present a major complication in patients with diabetes. Staphylococcus aureus is the most common single isolate in diabetic wounds. Humanbeta-defensin (hBD)-3 is antimicrobial active and appears to play a key role in the immune response. The present study aimed to analyse the effect of hBD-3 expression in a model of infected diabetic wounds. METHODS: Excisional wounds were created on the backs of Yorkshire pigs and Ad5-CMV-hBD-3 vectors were microseeded. Wounds were inoculated with S. aureus, covered with a polyurethane chamber and analysed for transgene expression, bacterial infection, re-epithelialization, wound contraction, wound fluid production and blood vessel formation. RESULTS:hBD-3-treated wounds showed a total bacterial load of 2.1 x 10(8) colony-forming units (CFU)/g tissue, versus 1.3 x 10(9) CFU/g tissue for controls (p < 0.001) at day 4. At day 12, no statistical difference could be detected. Re-epithelialization showed 75 +/- 15% wound closure for hBD-3 expressing wounds and 50 +/- 16% for controls (p < 0.01). hBD-3 expression was in the range 15-20 ng/ml of wound fluid during day 1-4. The lower dose of 2 x 10(9) Ad5-CMV-hBD-3 showed no effect, suggesting a dose dependency for hBD-3. CONCLUSIONS: In the present study, we show that hBD-3 expression significantly promotes wound closure in S. aureus infected diabetic wounds in a preclinical large-animal model. Furthermore, a ten-fold reduction of bacterial growth on day 4 was detected. These findings indicate that beta-defensin-3 may play a major role in diabetic wound healing and wound infections.
Authors: James K Chan; Johannes Roth; Joost J Oppenheim; Kevin J Tracey; Thomas Vogl; Marc Feldmann; Nicole Horwood; Jagdeep Nanchahal Journal: J Clin Invest Date: 2012-08-01 Impact factor: 14.808
Authors: Tianhong Dai; Gitika B Kharkwal; Masamitsu Tanaka; Ying-Ying Huang; Vida J Bil de Arce; Michael R Hamblin Journal: Virulence Date: 2011-07-01 Impact factor: 5.882