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Optogenetics utilizes light sensitive proteins to trigger biological functions by an external optical stimulus. It has been applied in numerous settings, including robotics, biotechnology, and several therapeutic approaches. The latter is of particular interest, as optogenetics provides the possibility to directly control cellular functions of excitable tissues, such as neurons and muscles, in a contact free manner by ion channels such as channelrhodopsin-2. In this context, optogenetics allows to create a human-implant interface, with an unprecedented performance. However, optogenetic therapeutic approaches are inhibited two conceptual constraints, limiting their clinical translation. (1) Precise and defined delivery of the stimulation light is restricted by scattering and absorption of the body’s tissue, limiting its resolution and thereby selectivity. (2) Optogenetics implies intrinsically a gene modification of the target tissue, raising issues concerning the effective in vivo delivery and the safety of the (viral) vectors applied. Biocompatible waveguides which in parallel can serve as cell encapsulation could provide a promising approach to circumvent these constraints. Encapsulation would ensure optical accessibility and encase the genetically modified cells. These constructs should guide and distribute the light as desired with minimal losses and they should also mimic the mechanical properties of the surrounding tissue to ensure compatibility and long-term stability. In this project, we present a study on poly(ethylene glycol) (PEGDA) based hydrogels as waveguides for optogenetic pacing of the heart. PEGDA is a non-biodegradable, biocompatible polymer with high transparency for visible wavelengths. Both optical and mechanical properties of hydrogels made from PEGDA derivatives are tuned to achieve compatibility with muscle tissue as well as optimal light guiding and distribution. The excitation light is coupled into the hydrogel with a biocompatible fiber. The design of the fiber-hydrogel contact must ensure efficient light coupling as well as mechanically stable binding of the fiber to the hydrogel construct. Properties of the hydrogel are mainly tuned by monomer length and concentration. Total internal reflection can be achieved by embedding a fiber-like hydrogel with a high refractive index into a second, low refractive index gel. Multi-component gels and different geometries are explored as additional ways to impact light distribution. After optimization, the hydrogel may be used to deliver light for the excitation of genetically altered cardiomyocytes for controlled contraction. This would pave the way for the development of a biohybrid, optogenetically driven pacemaker implant. On a long term perspective, hydrogel waveguides with embedded optogenetic excitable cells which functionally couple to the target tissue may serve as a general human-implant interface, with encased genetic modification and controlled, biocompatible light guiding to the target tissue.
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