Light-based therapies have been established for various indications, such as skin conditions, cancer or neonatal jaundice. Advances in the field of optogenetics open up new horizons for light-tissue in-teractions with an organism-wide impact. Excitable tissues, such as nerve and muscle tissues, can be controlled by light after the introduction of light-sensitive ion channels. Since these organs are generally not easily accessible to illumination in vivo, there is an increasing need for effective bio-compatible waveguides for light delivery. These devices not only have to guide and distribute the light as desired with minimal losses, they should also mimic the mechanical properties of the surrounding tissue to ensure compatibility. In this project, we are tuning both optical and mechanical properties of hydrogels from poly(ethylene glycol) derivatives to achieve compatibility with cardiac muscle tissue as well as optimal light guiding and distribution for optogenetic applications in the heart. The excitation light is coupled into the hydrogel with a biocompatible fiber. Properties of the hydrogel are mainly tuned by monomer length and concentration. Total reflection can be achieved by embedding a fiber-shaped hydrogel with a high refractive index into a second, low refractive in-dex gel. Multi-component gels and different geometries are explored as possibilities for waveguid-ing. Scattering microparticles enhance light distribution throughout the hydrogel for an even distri-bution in the target tissue. After optimization, the hydrogel may be used to deliver light to various tissues for optogenetics applications or phototherapy. The hydrogel waveguide is biocompatible and can be engrafted onto the target tissue. We are de-veloping a biohybrid device encorporating a hydrogel for light delivery and light-sensitive engi-neered cardiac tissue for implantation to treat cardiac arrhythmias. The cardiac tissue patches are produced from induced pluripotent stem cell-derived cardiomyocytes and could be made from the patient’s own cells in a clinical setting. This project evaluates the clinical relevance of optogenetics in cardiology and explores difficulties and opportunities for novel light-based therapies.