Optical Coherence Tomography Angiography Monitors Cutaneous Wound Healing under Angiogenesis-Promoting Treatment in Diabetic and Non-Diabetic Mice

Featured Application Optical coherence tomography angiography can provide biomarkers for vascular remodeling in preclinical wound healing studies. During wound healing, the rapid re-establishment of a functional microcirculation in the wounded tissue is of utmost importance. We applied optical coherence tomography (OCT) angiography to evaluate vascular remodeling in an excisional wound model in the pinnae of C57BL/6 and db/db mice receiving different proangiogenic topical treatments. Analysis of the high-resolution OCT angiograms, including the four quantitative parameters vessel density, vessel length, number of bifurcations, and vessel tortuosity, revealed changes of the microvasculature and allowed identification of the overlapping wound healing phases hemostasis, inflammation, proliferation, and remodeling. Angiograms acquired in the inflammatory phase in the first days showed a dilation of vessels and recruitment of pre-existing capillaries. In the proliferative phase, angiogenesis with the sprouting of new capillaries into the wound tissue led to an increase of the OCT angiography parameters vessel density, normalized vessel length, number of bifurcations, and vessel tortuosity by 28-47%, 39-52%, 33-48%, and 3-8% versus baseline, respectively. After the peak observed on study days four to seven, the parameters slowly decreased but remained still elevated 18 days after wounding, indicating a continuing remodeling phase. Our study suggests that OCT angiography has the potential to serve as a valuable preclinical research tool in studies investigating impaired vascular remodeling during wound healing and potential new treatment strategies.