Artificial red blood cells increase large vessel wall damage and decrease surrounding dermal tissue damage in a...

Artificial red blood cells (i.e. hemoglobin [Hb] vesicles [Hb-Vs]) function effectively as photosensitizers in flashlamp-pumped pulsed-dye laser (PDL) treatment for port-wine stains in animal models. Hb-Vs deliver more Hb to the vicinity of the endothelial cells. Both Hb-Vs and red blood cells absorb the laser energy and generate heat, supporting the removal of very small blood vessels and deeper subcutaneous blood vessels with PDL irradiation in in vivo experiments. Here, we analyzed the photosensitizing effect of Hb-Vs in PDL irradiation on large blood vessels and surrounding soft tissues. We histopathologically analyzed markers of damage to the large vessels and surrounding dermal tissue in a rabbit auricle model following PDL irradiation alone or subsequent to the addition of intravenous Hb-V injection. Markers were graded on a five-point scale and statistically compared. The changes in laser light absorption and reflection in a human skin model caused by the administration of Hb-Vs were evaluated using Monte Carlo light-scattering programs. Histological markers of damage to blood vessels were significantly greater in Hb-V-injected arteries and veins measuring 1-3 mm in diameter as compared with the controls. However, Hb-V injection significantly reduced PDL-induced necrosis and hemorrhage in the surrounding tissues. During computer simulation, photon absorption increased within the vessel layer and decreased around the layer. Intravenous Hb-Vs increase the extent of damage in larger vessel walls but significantly reduce damage to the surrounding skin after subsequent PDL irradiation. These beneficial effects are the result of improving vessel selectivity by Hb-Vs in vessels. Hb-V administration prior to PDL irradiation therapy could mechanically improve the outcomes and safety profiles of port-wine stain treatment protocols.