Hydrolytically Stable Thiol-ene Polymer Substrates for Neural Interface Devices

Bioelectronics devices can be described as the combination of materials and electronics to interface with biological systems, and are typically used to detect and modulate biological signals in order to control bodily functions with promise to treat and perhaps cure diseases. Neural interface systems represent a class of bioelectronic devices that facilitate connection between the outside world and the nervous system through conducting electrodes which transduce electric signals to and from the bioelectronic device (and thus to and from the body) to treat or help people with neurological disorders. One type of device used in neural interface systems today is composed of a substrate and one or multiple electrodes whose purpose is to add, remove or block information from various parts of the central or peripheral nervous system. The performance of the so-called electrode-tissue interface (or how the device connects to the nervous system) varies depending upon the nature of the electrode/substrate combination. A driving disadvantage of many typical electrodes fabricated on hard materials is the resulting inflammatory reaction that may lead to electrode failure or adverse signal recording, stimulating or blocking. Using polymers as a substrate, with a Young's modulus in the MPa range after insertion at an initially higher modulus, upon which to fabricate electrodes, has been proposed as a design mechanism to help address many of the mechanical mismatch issues associated with stiff materials. In particular, one class of materials has been explored extensively in this space over the past half-decade: thiol-based shape memory polymers. Thiol-ene/acrylate copolymers were introduced in 2012 to tackle several of the physical mismatch problems resulting in a half decade of efforts to understand effects of these materials on the underlying physiology acutely and sub-chronically in small animal models. Using shape memory polymers has led over the past half-decade to the optimization of devices (cortical probes, cochlear implants, nerve cuffs, spinal cord simulators and others) which are stiff enough to be effectively handled by surgeons, implanted, and subsequently demonstrated reduced stiffness after insertion into neural tissue and a different physiological response than materials which are always stiff. Currently, most of the commercially available monomers used in the design and fabrication of shape memory based neural interfaces contain chemical structures with ester functional groups, which increase the polymers’ susceptibility to hydrolytic degradation under moist conditions. Hydrolysis of polymer substrates can lead to many adverse effects for neural interfaces, producing specific by-products at different points after implantation. Therefore, the degraded polymer often is the culprit for worsening device performance: as a direct result of the ester-mediated degradation of these polymers, leakage channels develop through the device and negatively affect the subchronic and chronic electrical performance of devices. In this research, a series of novel thiol-ene formulations have been designed, formulated, polymerized and tested in actual devices. These new materials demonstrate a glass transition temperature and modulus similar to leading shape memory polymer neural interfaces in the published literature, but these novel formulations do not contain ester groups anywhere in the polymer network, allowing exploration of the hypothesis that this approach minimizes hydrolytic instability under the conditions to which neural interfaces are subjected. The synthesis of several new monomers was optimized and a novel polymer composition was designed and realized through photopolymerization from these new building blocks to have similar in vivo softening capabilities as previously reported polymers. Dynamic mechanical analysis (DMA) of the hydrolytically stable polymer reveals that the polymer has a glass transition temperature above body temperature when dry and below body temperature after being soaked in physiologically representative media such as phosphate buffered saline (PBS). Thus, the novel polymers in and around this resulting design space are able to soften under physiological conditions to a modulus which is much closer to the tissue than the as-inserted devices. To verify the improved stability of the new material against hydrolysis, accelerated aging tests were performed. Weight loss and mechanical properties were determined and compared to ester-containing polymer compositions. Resulting polymers are proposed as a candidate for translation into next-generation bioelectronic devices as substrates that help overcome a major limitation with previous shape memory polymer based neural interfaces.