Nanoporous semiconductor-enabled multi-site photostimulation for cardiac resynchronization therapy

University Of Chicago, Chicago IL

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Abstract

Project Summary A wide range of deformable biointerface devices are employed for the diagnosis, treatment, and monitoring of cardiovascular diseases by measuring physiological parameters, applying bioelectrical modulation, or delivering drugs. Despite preclinical advances in biotechnology such as optogenetics and cell-based biological pacing, non-genetic electronic methods remain the dominant method for treating cardiac rhythm disorders. Semiconductors, in particular, have emerged as a potentially useful tool for non-genetic cardiovascular research, including field effect transistor-based electrophysiology sensing, light-driven cardiac population activation, and electronics-integrated cardiac tissue engineering. We recently published several photoelectrochemical methods for optically modulating cardiac activity in cultured cells as well as in adult rodent models ex vivo. The use of light to modulate cardiac tissue with an intensity comparable to that used in optogenetics has been demonstrated. In this work, Tian will work closely with Hibino to expand and strengthen our newest photoelectrochemical biomodulation system, porosity-based silicon heterojunctions, for multi-site, leadless, nongenetic, and optoelectronic modulation of cardiac tissues. Specifically, we will design, construct, and test a selection of heterojunctions based on porosity for optical modulation of cardiac tissues. We will synthesize core/shell nanowires, core/shell microparticles, and bilayer membranes that contain non-porous/nanoporous heterojunctions. To improve the stability of the heterojunctions under physiological conditions, we will apply atomic layer deposition to passivate the silicon surfaces. We will modify the material surface with metal or metal-oxide catalysts to enhance signal transduction. To support the silicon heterojunctions, we plan to use soft matrices such as polymers and hydrogels, which will enhance biocompatibility and signal transduction at the biointerfaces. We will also fabricate biocompatible optical fibers for use in in vivo photostimulation experiments. In order to enable multi-site optical pacing, we will develop, assemble, and test the software, mechanical, electrical, and optical components. Afterwards, we plan to validate the scanner's performance, such as its accuracy, scanning speed, and power delivery, followed by the photostimulation tests ex vivo. The device will then be tested to determine its biocompatibility in a rat model, followed by testing heart pacing in acute and chronic settings using single-chamber, dual-chamber, and multi- site stimulations in a pig model. We will test our hypothesis that deformable and biocompatible heterojunction devices can be used for multi-site cardiac resynchronization therapy triggered by optical signals. The proposed research can define a new treatment option for cardiac modulation. Incorporating freestanding and photosensitive semiconductors with excitable cells and tissues will result in biointerfaces that can be controlled by light. The new designs for semiconductor-based biointerfaces would allow for wireless, nongenetic, multiscale, and random access photomodulation.