Diabetes affects more than 29 million people in the United States, and this number is projected to double or triple by 2050. This disease causes many physiological complications, such as diabetic foot ulcers. Such impaired wound healing in diabetic patients is caused by a variety of physiological abnormalities, one of which is poor microcirculation, which is essential for normal wound healing.
A team from the Beckman Institute for Advanced Science and Technology in the USA investigated the healing mechanisms of a novel topical ointment for diabetic wounds that is capable of promoting angiogenesis by inducing local physiological conditions that mimics hypoxia. Angiogenesis has a crucial role in many diseases and physiological responses, including wound healing. The topical treatment that was investigated mimics hypoxia via inhibition of prolyl hydroxylase, a key regulator of hypoxia-inducible factor (HIF).
Currently, characterizations of wound healing and associated treatments rely heavily on visual inspection, digital photography and ex vivo analysis. In recent years, several optical imaging techniques have proven beneficial in observing key biological events, both in vivo and ex vivo, in processes, such as wound healing, at resolutions unparalleled by conventional techniques.
In this study, phase-variance optical coherence tomography (PV-OCT) and fluorescence lifetime imaging microscopy (FLIM) were utilized to track the regeneration of the microvasculature network and the change in cellular metabolic activity, respectively, in wounded and healing skin in diabetic (db/db) mice.
PV-OCT imaging and analysis show that the ear wounds in mice treated with this angiogenesis-promoting agent demonstrate a significant increase in vessel density. While additional studies are required to further understand the larger number of complex healing mechanisms involved in the skin wound healing process, the cross-modality correlation between PV-OCT and FLIM presented in the study successfully relates the increase in vasculature density to the relative changes in cellular metabolism in living animals.
“Insights gained in these studies could lead to new endpoints for evaluation of the efficacy and healing mechanisms of wound-healing drugs in a setting where delayed healing does not permit available methods for evaluation to take place” concludes team member Stephen A. Boppart.