Diabetic foot wounds are a major cause of morbidity and mortality 1 and, even in centers in which nearly half the patients with moderate or severe wounds undergo revascularization, these wounds have median healing times of 6 months or more, with one-third requiring amputation.
2Such resource-intensive care is simply not available in most of the world, where "water or even gauze dressings may be scarce or not available".1 Therefore, topical formulations to assist in wound healing are of significant interest: they can be simply applied, are not invasive, do not require advanced training for application, and can be used in an outpatient setting at relatively low cost. Moreover, many wounded patients have gone through exhaustive treatment with offloading, daily wound care, and invasive procedures, all without successful healing.
3Topical agents for wound healing have been described and used since antiquity.The study reported in the current issue of the Journal of Diabetes 4 is therefore of interest in exemplifying the importance of research to find novel approaches to effective topical agents. Opiate receptors are present in the skin and stimulate keratinocyte formation.5 Gupta et al. 4 used a delayed excisional wound-healing model in Zucker diabetic fatty mice to compare topical fentanyl with a saline-containing cream, finding significantly greater wound closure at 18 and 28 days, with a reduction in wound edema and increased re-epithelialization, vascularization, and granulation tissue formation with greater levels of collagen deposition. There is emerging data for the use of a number of topical antimicrobial, debriding, angiogenic, and cellular therapies as agents for wound healing.6 Probiotics and nitroglycerin have been proposed as offering therapeutic potential. 7,8 Oxygen has been studied using a variety of application methods.9 Natural substances that have been studied include preparations based on beehive protectant propolis, 10 aloe vera, 11 Momordica charantia fruit, 12 and kiwifruit.13 A recent meta-analysis suggested benefit of platelet-derived growth factor, 14 and both epidermal growth factor 15 and macrophage-stimulating agent 16 have been studied as additional biological approaches.Although there is much interest in these topical treatments, none appears yet sufficiently well validated to be ready for widespread use. Topical honey for promotion of wound healing was studied in a Cochrane Database Systematic Review, which reported no benefit of such an approach. 17