Anti-Vascular Endothelial Growth Factor (Bevacizumab) Therapy Reduces Hypertrophic Scar Formation in a Rabbit Ear Wounding Model

Abstract

Background Hypertrophic scarring is a pathological condition that occurs after trauma or surgery. Angiogenesis occurs more often with hypertrophic scarring than with normotrophic scarring. The regulation of angiogenesis is one of the key factors in hypertrophic scar management. Vascular endothelial growth factor (VEGF) is an essential factor in the angiogenetic response. This study investigated whether decreasing the level of VEGF is effective for treating hypertrophic scarring. Methods Ten 8-week-old female New Zealand white rabbits were included. Four defects were created on each ear by using a 6-mm punch. Bevacizumab (Avastin, Roche Pharma, Basel, Switzerland) was administered in one ear and normal saline was administered in the other ear. Treatment was administered starting on day 2, every 2 days, until day 14. The levels of VEGF were measured using enzyme-linked immunosorbent assay on day 10 and histologic results were analyzed on day 40. Results Bevacizumab induced-defects showed less hypertrophic scarring when compared with the control group as measured by the scar elevation index (SEI) and loose collagen arrangement. The SEI in the experimental group was 1.89 +/- 0.13, compared to 1.99 +/- 0.13 in the control group (n=30, P=0.005). Additionally, the VEGF level was lower (38.72 +/- 11.03 pg vs. 82.50 +/- 21.64 pg, n=10, P=0.001) and fewer vessels existed (8.58 +/- 0.76 vs. 7.2 +/- 1.20, n=10, P=0.007). Conclusions Preventing excessive angiogenesis is effective for preventing scar formation, especially with hypertrophic scarring. Although it is not an approach that is sufficient alone for the management of scarring, it may be one of several important strategies for scar treatment.