The Rational Design and Deployment of Electrocatalytic Oxygen Generating Platforms and Their Applications in Biomedical Engineering

In recent decades, there have been remarkable advancements in bioelectronics for recording, stimulation and input/output systems. The progress in electronic devices for biointerfaces has broadened our knowledge in inter/intracellular communication with electrical signals, establishing the field called electrophysiology. Chemical cues are another important means for cellular interaction. However, chemical interaction between and/or within cells and tissues have been underexplored because of the complexity of chemical environments in cellular networks. To understand physiological chemical composition and modulate it through chemical interrogation, researchers have developed platforms via electrochemical techniques and microfluidics. Nonetheless, such conventional approaches require external sources of modulating agents as well as invasive backend connections. In this regard, the on-site generation of biochemicals via catalysis has intrigued scientists’ attention. Small molecular factors, for example, oxygen, carbon monoxide and dioxide, nitric oxide, can be readily evolved in physiological fluids by redox reactions of precursors. Among various molecules in physiology, oxygen has been regarded as one of the most important chemicals. Its remarkable oxidative capability enables extracting chemical energy from nutrients in an efficient way. Therefore, aerobic respiration is critical to maintaining metabolism of most forms of organisms, particularly higher animals, such as humans, that demand a great amount of oxygen to support complex biological activities. For this importance of oxygen, living matters have been evolved to maintain physiological oxygen availability in their bodies. Hypoxia inducible factors (HIFs) are the mediators for the oxygen-related homeostatic physiological phenomenon with their oxygen sensitivity. With the ubiquitousness of HIFs, oxygen is associated with a plethora of biological events, triggering the expression of several hundred biomarkers at different levels. Therefore, electrocatalytic oxygen generation could offer tremendous opportunities for biological and biomedical applications, because oxygen is prevailingly involved in many physiological cascades. While oxygen can be produced by electrocatalytic reaction of abundant water molecules in the body, the energetic cost of water electrolysis has imposed challenges for in situ generation of oxygen. Although electrocatalytic water decomposition, namely water splitting, has been reported extensively in energy science, the establishment cannot be translated into biological applications due to the nature of neutral pH in physiology and sophisticated chemical composition. In this dissertation, I developed an oxygen-generating electrocatalytic bioelectronic platform and deployed them in different biomedical applications. First of all, the devised bioelectronics were employed in high-density implantable cell therapies to support their metabolism via exogenous oxygen delivery. As a biocompatible and efficient electrocatalyst, iridium oxide was selected, and it was engineered to possess large surface area nanostructured electrodes. Based on finite element analysis, the catalyst was patterned for uniform distribution of generated oxygen. Validated in terms of selective oxygen production without detrimental byproducts within defined safe potential range, the invented electrocatalytic on-site oxygenator (ecO2) demonstrated improved cell viability as well as therapeutic peptide secretion for up to 21 days in vitro and in vivo. Note that this is the very first report of on-site electrocatalysis for chemical modulation of physiological processes. The developed electrocatalytic bioelectronics were improved as a fully implantable form factor for durable therapeutic release to manage chronic diseases. To accomplish the durable electrocatalytic arrays, the synthesis conditions of SIROF, the deployed electrocatalytic material, were fine-tuned for optimized reactivity and stability. Microfabricated catalytic arrays were assembled with batteries and circuits for Bluetooth communications and powering the water electrolyzer. The entire system was protected by multilayered encapsulation from moisture- and salt-abundant physiological settings. Implanted in animal models, the bioelectronics were able to sustain multiplexed therapeutic delivery from high-density and high-loading therapeutic cell capsules. Lastly, the feasibility of oxygenation in tissues was investigated. On-site oxygenation in tissue mimicking cell-laden hydrogel was able to address necrotic core formation which originates from diffusion limitation of oxygen. The reduced HIF-1α levels in oxygenated tissues corroborated that electrocatalytic on-site oxygenation indeed alleviates hypoxic stress in large scale engineered tissues. As demonstrating in vitro and in vivo, this thesis suggests that on-site electrocatalytic oxygen generation can address underlying issues in cell transplantation and tissue engineering. To translate this technology into clinical interventions, the system needs to be verified in large animal models such as non-human primates as well as clinical trials in human beings. In order to advance technology, another important aspect is to demonstrate it in mammalian and human tissues, for instance, pancreatic islets, muscle tissues and organoids. The maintenance of harvested tissues or cultivated tissues will open up the new horizon not only in fundamental biological studies but also in therapeutic purposes. Additionally, the successful demonstration of on-site catalysis alludes that other small molecular factors can be generated in situ for chemical modulation in physiology such as neurological systems.