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

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

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 251 KB
• Volume: 11
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.1287

✦ Synopsis

Abstract

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 × 10^8^ colony‐forming units (CFU)/g tissue, versus 1.3 × 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 × 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. Copyright © 2008 John Wiley & Sons, Ltd.