Details

Autor(en) / Beteiligte

• Hirsch, Tobias
• Spielmann, Malte
• Zuhaili, Baraa
• Fossum, Magdalena
• Metzig, Marie
• Koehler, Till
• Steinau, Hans-Ulrich
• Yao, Feng
• Onderdonk, Andrew Bruce
• Steinstraesser, Lars
• Eriksson, Elof

Titel

Human beta-defensin-3 promotes wound healing in infected diabetic wounds

Ist Teil von

• The journal of gene medicine, 2009-03, Vol.11 (3), p.220-228

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2009

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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 × 108 colony‐forming units (CFU)/g tissue, versus 1.3 × 109 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 × 109 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. Copyright © 2008 John Wiley & Sons, Ltd.