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

Abstract

BackgroundHypertrophic 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.MethodsTen 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.ResultsBevacizumab 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).ConclusionsPreventing 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.

Pigment epithelium‐derived factor attenuates angiogenesis and collagen deposition in hypertrophic scars

“…24,[55][56][57] Some studies demonstrate that the reduction in the hypertrophic scar is associated with a decrease in angiogenesis, and a few have directly explored the use of antiangiogenic therapies, including anti-VEGF and endostatin, to reduce scar formation in the rabbit model. [58][59][60] Together with the current study, then, a growing body of data supports the concept that robust angiogenesis spurs fibrosis in skin wounds, and that inhibition of angiogenesis, at least with the subgroup of agents that decreases VEGF activity, can reduce scar formation.…”

Systemic factors that shape cutaneous pathological scarring

“…This effect associated with the expected drop in tissue VEGF level. 19 Similarly, Wang et al showed that when rabbits with nascent ear hypertrophic scars were injected topically with recombinant human endostatin, the scars had lower scar elevation index values, less connective tissue, fewer microvessels and fibroblasts, and smoother collagen fibers. These effects associated with lower VEGF levels in the scars.…”

Photodynamic Therapy Versus Glucose for the Treatment of Telangiectasia: A Randomised Controlled Study in a Rabbit Ear Model

“…Rabbit ear is a commonly used experimental model for vascular treatment. 14,15 However, the small vascular net seen between central artery and collecting marginal vein is actually arteriovenous communications, used physiologically for the animals' temperature control. 16 These vessels have high blood flow, which makes their sclerosis a challenge in some therapies.…”