Characterization of atmospheric pressure needle plasma source and evaluation of its effect on angiogenesis in wound healing progress by using angiogenic optical coherence tomography

Abstract

Non-thermal atmospheric pressure plasma (APP) refers to cold plasma that is not in thermodynamic equilibrium. The biomedical applications of non-thermal APP in wound healing have been attracting considerable attention recently for its promising results. Angiogenesis forming new micro-vessels is a key factor of the wound healing process. Previous researchers have reported that APP stimulates wound healing through plasma-induced angiogenesis. However, very little is known about how plasma influences the angiogenesis in the wound healing process even though detailed characterization of plasma-induced angiogenesis during wound healing is crucial in understanding the effects of plasma treatment and therapeutic application. To reveal the angiogenesis effect of APP, we developed optimized atmospheric pressure needle plasma (APNP) source and observed its effect on the angiogenesis in wound healing by using angiographic optical coherence tomography (OCT) as follows. First, we optimized the APNP as considering its effect on in vitro tissues characterized by non-invasive OCT as well as electrical, optical, and thermal diagnostics. Through the optimization, treatment window of APNP was obtained. In the optimization process, we observed the acute plasma effect on vascular flow. Second, we observed angiogenesis induced by the optimized plasma treatment in the wound healing process of punched ear mouse by non-invasive in vivo angiographic OCT imaging methods. The angiographic OCT images revealed that the plasma effect penetrates into the wound surface and induces angiogenesis around the vascular wound boundary. The vascular wound area of plasma treated wound decreased as compared to that of control. Furthermore, the vascular density area ratio of the plasma-affected region around the vascular wound boundary region was higher than that in the unaffected region. This non-invasive optical approach would be a useful for evaluating the plasma-induced angiogenesis and provides further insight into biomedical plasma application.