Optical excitation of organic semiconductors as a highly selective strategy to induce vascular regeneration and tissue repair

Therapeutic neovascularization represents a promising strategy to rescue the vascular network and restore organ function in cardiovascular disorders (CVDs), including acute myocardial infarction, heart failure, peripheral artery disease, and brain stroke. Endothelial colony forming cells (ECFCs), which are mobilized in circulation upon an ischemic insult, are commonly regarded as the most suitable cellular tool to achieve therapeutic neovascularization. ECFCs can be genetically or pharmacologically manipulated to enhance their vasoreparative potential by boosting specific pro-angiogenic signalling pathways. However, optical stimulation represents the most reliable approach to control cellular activity because of its high selectivity and unprecedented spatio-temporal resolution. Herein, we discuss a novel strategy to drive ECFC angiogenic activity in ischemic tissues by combining geneless optical excitation with photosensitive organic semiconductors. We describe how photoexcitation of the conducting polymer poly(3-hexylthiophene-2,5-diyl), also known as P3HT, stimulates extracellular Ca2+ entry through Transient Receptor Potential Vanilloid 1 (TRPV1) channels upon the production of hydrogen peroxide (H2O2) in the cleft between the nanomaterial and the cell membrane. H2O2-induced TRPV1-dependent Ca2+ entry stimulates ECFC proliferation and tube formation, thereby providing the proof-of-concept that photoexcitation of organic semiconductors may offer a reliable strategy to stimulate ECFCs-dependent neovascularization in CVDs.