Optogenetic tools for the development of a biohybrid pacemaker

Optogenetic tools are opening up new opportunities for biological and biomedical sciences and expand the horizon for novel therapeutic approaches. The introduction of light-sensitive proteins such as Channelrhodopsin-2 (ChR-2) provides a control switch that allows for the regulation of diverse cellular functions by light impulses. Optogenetically modified cardiomyocytes can be stimulated to contract in response to one-photon stimulation at blue wavelengths or two-photon stimulation in the NIR spectrum. For this work, bioartificial cardiac tissue patches have been developed using ChR-2 expressing human iPS-cells and matrix proteins. In a collaborative approach, a hydrogel is designed to deliver stimulating light from a fiber to the tissue patch. Upconversion nanoparticles are included in the construct to allow for the use of longer wavelengths and thereby a higher penetration depth. The final construct is planned to be implanted onto the myocardium and coupled to the cardiomyocytes in vivo to enable light-controlled and pain-free pacing and defibrillation of the heart.