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Innovative Biodegradable Poly(ionic liquid)s for Bioelectronics

Periodic Reporting for period 1 - iPILs4Bionics (Innovative Biodegradable Poly(ionic liquid)s for Bioelectronics)

Reporting period: 2018-09-01 to 2020-08-31

Bioelectronic systems have experienced tremendous growth, ensuing a variety of bioelectronic devices that can offer improved healthcare conditions, such as biosensors, pacemakers, neural interfaces, ion-pumps, etc. Nevertheless, this field is limited by the materials that transduce signals across the electronic/biology interface. For instance, in electrodes for electrophysiology, the coatings are required to be so be, highly conductive, biocompatible and able to decrease electrode/skin interface impedance, so that they can be suitable for long-term recordings. The existing conductive materials struggle to meet these demands; hence, it is still a challenge to fabricate such systems.

Poly(ionic liquid)s as electrolytes have recently attracted much attention in the development of iongels. These soft ionic materials combine the excellent ionic conductivity and low volatile ILs with the mechanical properties of PILs. However, most of the developed PILs were based in non-biodegradable polymeric backbones, which limit the application of the materials in vivo. Thus, it is of vital importance to add new properties to iongels, like biodegradability and biocompatibility, before their application in the healthcare sector.

This project addresses these issues through the development of innovative biodegradable poly(ionic liquid)s for bioelectronic devices. For this purpose, the chemistry of biodegradable poly(ionic liquid)s or other functional polymers is combined in an original way with readily biodegradable ionic liquids in order to obtain different materials for bioelectronics. It is easy to foresee that the ionic liquid-based materials here developed will represent a clear breakthrough in the design of advanced soft ionic electrolytes for biomedical applications.

Consequently, this project is potentially high social impact and it will lead to the development of new materials to improve the performance of bioelectronic devices interfaced with human body, ensuring improved quality of human’s life. Higher-quality data will enable the investigation of better solutions for treating pathologies such as epilepsy and cancer, as well as to monitor and detect important diseases related to the heart (i.e. arrhythmias) and muscular problems.

Overall, the focus of this project is to synthesize new biodegradable poly(ionic liquid)s, opening the door to the creation of a new generation of innovative soft ionic materials, and determine their potential to improve the performance of bioelectronics devices.
To start this project, we focused on the development of poly(ionic liquid)s combining cationic polyesters backbones. Then, and in addition to what was initially projected, alternative synthetic pathways were proposed in order to obtain other poly(ionic liquid)s and ionic liquids having biodegradability and biocompatibility potential. In particular, novel ionic liquids and poly(ionic liquid)s combining neurotransmitters were proposed, considering their great interest for ion pump applications. On the other hand, new functional polymers and biocompatible/biodegradable ionic liquids were also synthesized to be used as precursors in the preparation of semi-solid iongels for bioelectronic devices. Although the small deviations and additional work performed, the key objectives were achieved and optimized protocols for the reproducible synthesis of several monomers and polymers were obtained.

The structural characterization of all the prepared materials was mainly investigated by NMR and FTIR. In order to better understand different structure-property relationships, complete characterization data was obtained by investigating the thermal behaviour, mechanical stability, rheological behaviour and morphology of the prepared materials. Biocompatibility tests and degradation studies were also carried out.

The use of the prepared ionic liquid-based materials in bioelectronic devices was investigated, particularly in electrodes for cutaneous electrophysiological recordings. Free standing conductive iongel materials were prepared and their ionic conductivity with temperature and time were studied. Furthermore, a pressure and strain sensor platform was fabricated to demonstrate the sensory capability of the materials. Artificial skin devices with the ability to sensitively detect stimuli, such as mechanical force and temperature changes, have been intensively investigated for applications in soft robotics and bioelectronics.

Finally, ionic liquids and poly(ionic liquid)s combining neurotransmitters were used to develop a new method to significantly limit drug leakage from electrophoretic drug delivery devices, which is one of the major challenges these bioelectronic devices are facing. It is worth mentioning that this novel approach can be universally applied to any device architecture to extend the lifetime of drug delivery implants while making them safer for chronic implantation.

During this project, the ER published 8 research articles (Membranes 2018, 8, 124; Ind. Eng. Chem. Res. 2019, 58, 2017-2016; Sep. Purif. Technol. 2019, 222, 168-176; Ind. Eng. Chem. Res. 2020, 59, 308-317 in I&EC Research 2019 Class of Influential Researchers Special Issue; Membranes 2020, 10, 46; ACS Sustain. Chem. Eng. 2020, 8, 5954−5965; Macromol. Biosci. 2020, 2000119; ACS Sustainable Chem. Eng. 2020, 8, 7087−7096) and 1 review article (J. Phys. Chem. B 2020, DOI: 10.1021/acs.jpcb.0c04769). In addition, 1 research article (Advanced Science) and 1 review (Prog. Mat. Sci.) were submitted and are under review. Two more manuscripts with the remaining results of the project are under preparation.

The ER attended two international conferences to present 2 posters and 1 invited lecture. The ER also gave an invited seminar and participated in 2 outreach activities.
The main outcome of this project was the design of innovative ionic liquid-based materials, holding great potential for bioelectronic devices interfaced with human body. It is worth mentioning that the development of advanced soft-ionic materials is of vital importance to improve the efficiency of biolectronic devices, which are currently used to monitor and investigate solutions for important diseases such as Parkinson, Alzeimer, Epilepsy or peripheral nerve injury, to name a few. Thus, this project definitely contributed to ensure healthy lives and promote well-being for all at all ages, which is the Goal 3 of the 2030 Agenda for Sustainable Development.

The global bioelectronics and biosensors market was valued at USD 11.39 billion in 2013 and it is likely to be estimated over USD 25 billion by 2023. This is an indication of the remarkable impact of developing improved bioelectronics tools. It is clear that innovation is expected to drive the industry growth and increase profits over the forthcoming years.

As main result of the research work carried during the two years of the project, new ionic liquid-based materials were synthesized with unique and improved properties. Some applications in bioelectronics were successfully tested and we expect that many more will be also tried due to the high potential of these materials to be employed in other biomedical application, such as new bioresponsive surfaces, biomaterials, and drug delivery systems, among others.
Project work plan