Surgical trial of novel pro-angiogenic compounds that may accelerate wound healing

Abstract

Chronic wounds and wounds that are difficult to heal are a major concern for Australian healthcare expenditure and a source of misery for those who suffer from them. For example, in Australia in 2012, there were an estimated 433,000 people suffering from these, costing an estimated AUD2.6 billion dollars for the year to July. Novel ways of healing wounds are continually being sought. Two strategies used to accelerate wound healing are augmenting angiogenesis and through manipulation of wound healing growth factors. The method of stimulating angiogenesis proposed in this research was through the use of a topically applied flavonoid or lignan molecule. Two compounds in particular, the lignan erythro-guaiacylglycerol-8-O-4’-coniferyl alcohol (T1) and the flavonoid naringenin, have demonstrated pro-angiogenic activity based on in vitro testing but they had not been trialled previously in vivo.

C57BL/6J mice were used in techniques building on previous studies. Wounds were created with a control, positive control, and T1 and naringenin topically applied at varying concentrations. The compounds tested were applied at 3-day intervals, aiming for wound healing within 12 days. A second group was used to analyse the wounds and compounds trialled at day 3 after wounding, the day of maximal angiogenesis. The wounds were recorded and measured using pictorial and digital-image analysis. Results showed that both the flavonoid (naringenin) and the lignan (T1) when applied to wounds actually increased the size of the wounds and the length of time required for the wounds to heal. Subsequent histological analysis revealed that wounds treated with both T1 and naringenin, although not healing faster, produced higher amounts of granulation tissue and collagen deposition. Based on these data it is hypothesised that the above compounds caused an excessive deposition of granulation tissue, preventing effective wound healing. Although the wounds did not heal effectively, the results obtained from this study may be useful when applied to wounds that are difficult and slow to heal, such as diabetic ulcers.

In conclusion, further studies are required to confirm that these novel compounds increase angiogenesis, granulation tissue and collagen deposition within wounds. If so, new studies to find optimal dosage and application regimes may provide useful approaches to accelerating wound healing in the future. Show more