Catalina Vallejo-Giraldo, PhD candidate at CÚRAM, the Science Foundation Ireland Centre for Research in Medical Devices based at NUI Galway, has recently published the results of her work in the prestigious journal Advanced Functional Materials (AFM), with an impact factor of 12.12. Vallejo-Giraldo’s research focuses on the modification of implantable electrode systems to improve their performance when used, for example, in neural recording and in deep brain stimulation in patients with neurological disease such as dystonia and Parkinson’s disease. Deep brain stimulation (DBS) involves implanting stimulating electrodes into deep brain areas. Vallejo-Giraldo’s work explores the development of functionalised coatings for these electrodes through the use of physical, chemical and biochemical approaches for neural interface applications to enhance neuron/electrode integration in vitro, and as further functionalisation strategies for subsequent ex-vivo and in-vivo evaluation. Specifically in this case, she used a simple bench-top electrochemical method called an anodisation process to formulate anodised indium tin oxide (ITO) coatings/films with altered roughness, conducting profiles, and thickness through the application of differential current densities ranging from 0.4 mA cm-2 to 43 mA cm-2. In addition, each of these anodised ITO coatings was examined as to neural cell adhesion and network functionality as well as to their effect on glial scar modulation. The modification of implantable electrodes for neural stimulation such as for DBS applications has been a major focus of neural engineering research over several decades. Functional neuroelectrodes that support intimate contact with the tissue of the nervous system for long-term stimulation/recording performance and therapy, should remain functionally stable in situ to achieve optimum therapeutic benefit. “A common occurrence following electrode implantation is the formation of a glial ‘scar’ around the implant” explained Vallejo-Giraldo. “This causes the signal strength to decrease and adjacent neurons to move away from the electrode due to the surrounding region of gliosis, and thereby compromises the efficacy of a stimulating/recording system.”

Research findings

Through her research, it was shown how the ITO anodised coatings were produced with a low specific current density (0.4 mA cm-2), increased primary neural cell survival, modulation of glial scar response, and promotion of neural network activity when in situ with primary neural mixed cell populations. Of note is that these specific coatings formed with the lowest current density showed, in addition, a low impedance profile with a high charge storage capacity, key characteristics for future stimulation applications. Surface modification of ITO via anodisation has not yet been explored as a method to enhance cytocompatibility, cell adhesion and functionality in neural interface systems. Furthermore, the effects of ITO anodisation on coating/film electrochemical impedance and topography remain unknown. Catalina’s research, in fact, elucidated important material effects with regard to anodisation current densities on ITO film-surface morphology, electrochemistry and cytocompatibility for the generation of neural interfaces with superior electrical and biological characteristics. The biomaterial-tissue interface is not a simple description of a-boundary, but rather is a dynamic interface involving both the localised reaction of the surrounding tissue to the materials and the material adaptations within the physiological environment. Thus, active research in the field has focused on both the foreign body reaction and the long-term performance of biomaterials in a combined effort to drive the functionalisation of next generation implantable devices. “My research aims to develop a way to improve the efficacy of these devices, through functionalisation techniques,” Vallejo-Giraldo added. Traditionally, chemically inert conductors such as gold, platinum and iridium, as well as semiconductors such as silicon, have been widely employed as electrode systems in both clinical and research settings. However, nonmetallic electrically conducting biomaterials, including inherently conducting polymers and polymer composites have been explored as neuroelectrode alternatives in an effort to promote chronic functionality and enhanced biocompatibility. Further, multifunctional innovative manufacturing and polymer synthesis methods have driven the development of physicochemical modification, facilitating the delivery of bioactive molecules and drugs that can be immobilised on the substrates, further diversifying the potential of neuroelectrode biomedical applications.

Challenges of PhD research

Vallejo-Giraldo’s journey through her PhD was not without its challenges. “During my first year, I was entirely dedicated to learning the basics of electrochemistry and electrodeposition so as to investigate the process of electrodeposition of poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymer materials and characterise them in terms of their physical, electrical and biological properties. “ITO was the conductive substrate selected for this preliminary work, due to its low cost relative to platinum (Pt) materials. At that time, I was given access to a very old but hardly used Potentiostat, a Princeton Applied Research electrochemical Potentiostat/Galvanostat model 263A running Verastudio software,” she continued. After almost a full year of work, and after putting together the chemical data obtained from the large amount of anodised ITO coatings made with this machine and submitting work to a journal in the field, she realised that there were lots of matters to address. “While the comments from the journal were negative, they were also extremely helpful in illuminating concepts such as overoxidation of the deposited coatings,” said Vallejo-Giraldo. In retrospect, and in reviewing the set-up and by using our own Potentiostat acquired that year, she came to understand that the Princeton Applied Research electrochemical Potentiostat/Galvanostat model 263A was programmed with a reversed electrode configuration. This resulted in the anodisation of the ITO and not the electrodeposition of PEDOT– precisely the opposite of what she wanted to achieve. Vallejo-Giraldo continued: “At that point, my electrochemistry experience could be summarised in a comment made to me by an important professor in the electrochemical field: ‘Electrochemistry can be a black hole at times.’ But it was also a good reminder that serendipitous discovery and enlightening errors provide valuable learning.” Commenting on her work, Vallejo-Giraldo’s supervisor Dr Manus Biggs, principal investigator at CÚRAM said: “Catalina is extremely dedicated and passionate about her work, and at the time the ITO process was confusing, frustrating and quite demotivating for her. But, in the end, we’ve learned a lot from this. “A research career is full of educative errors, and this process was crucial in helping to illuminate some of the bases of her work in conducting polymers, and eventually resulted in the development of a process to formulate these anodised ITO coatings – work that’s still ongoing at my lab,” he added.

Further studies with neural microelectrodes

This work provides a useful benchmark for anodisation conditions for further studies with neural microelectrodes, micropatterning and biochemical functionalisation. This part of Vallejo-Giraldo’s research has shown that anodisation offers the ability to modify ITO coatings and may provide an easier approach to the generation of electrode coatings with differential regions of charge conductance and cellular function capacities. It can be hypothesised that anodisation with varying current densities may be employed to deposit insulator and charge carrier regions on a single electrode system, providing cytocompatible and functional coatings for implantable thin-film ITO devices. Congratulating Vallejo-Giraldo on her work, Prof Abhay Pandit, scientific director of CÚRAM, said: “Ultimately, what we’re trying to do at CÚRAM is to improve quality of life for patients with chronic illnesses through the development of new and enhanced implants and devices. It’s fantastic to see how our PhD candidates are contributing significantly to the knowledge base in this area.” Journal reference: Catalina Vallejo-Giraldo’s paper, ‘Preparation of Cytocompatible ITO Neuroelectrodes with Enhanced Electrochemical Characteristics Using a Facile Anodic Oxidation Process’, was published in the Advanced Functional Materials Journal earlier this year.