Encapsulating TiO2 thin films grown via Atomic Layer Deposition for biocompatible UV-activated neuronal interfaces

The development of smart implantable medical devices, focused to neuro-stimulation and/or recording with high resolution and long-term neuronal activity, are gaining a powerful importance in Neuroscience, aiming to a deep study of cerebral functions and in the treatment for neurodegenerative diseases, which are closely linked to an increase in the number of elderly people. Alzheimer, senile dementia, Parkinson's movement disorders, and other dyskinetic pathologies are constantly increasing and strongly connected to age, slowly evolving, characterized by a progressive and irreversible degeneration of neuronal system [1]. Others, such as epilepsy, cerebral stroke, and spinal injuries have recently encountered important and powerful advances in neurostimulation for therapy and rehabilitation. Currently, there are no specific therapies with a heavy impact on caregivers, health, and care system [2,3]. However, in the recent years, neurostimulation has gained more and more importance as a complementary approach or, in some cases, replacement of drug treatments. In the wider framework of bioelectronics, the present work tackles the urgent need of miniaturized interfaces between living and artificial systems (neuronal cell/CMOS-based specimen), consisting of highly biocompatible materials for applications in smart biosensors, characterized by long-term endurance and stability to mimic as better as possible the natural interaction with the native organ to restore functionality (neurobiohybrids) [4,5]. Specifically, thanks to the exploitation of Nanotechnology, the proposed research aims to understanding the ALD potentialities for downscaling synthesis of highly conformal and biocompatible dielectric TiO2 thin films, both focusing the attention on material biocompatibility at neuron/biomaterial interface, as well as satisfying the dielectric properties of the interfaces. The deposition and characterization of nanostructured dielectric TiO2 coatings via Low Pressure-ALD (LP-ALD) with a controlled composition, structure, and conformality have been carried out. The control of all the film properties combined with the development of an easy UV surface functionalization protocol to induce highly wettable and encapsulating surfaces was of crucial importance for the response of the prototype titania interfaces to be tested. Wettability, biocompatibility, preliminary electrochemical, and electrophysiological behavior of the materials were analyzed. Moreover, the optical properties of the grown thin films were analyzed by spectroscopic ellipsometry to infer porosity and photoactive defects that can also play a role in biocompatibility. Aiming to evaluate the functional biomedical applications of the ALD-deposited TiO2, neuronal biocompatibility in-vitro tests were probed. In this regard, to study the influence on cell adhesion, growth, and progress, the simple surface functionalization method by using UVC radiation has been developed obtaining highly wettable surfaces. In-vitro neuronal biocompatibility of the encapsulating titania was tested by plating rat hippocampi neurons and monitoring their development and morphology in culture before and after UV exposure. TiO2 thin films subjected to UV pre-treatment were highly biocompatible: neurons displayed a development and morphology comparable to neurons seeded on standard Petri dishes. To establish the efficacy of the capacitive behavior of the deposited prototypes, a preliminary electrochemical characterization was carried out in Simulated Body Fluid (SBF) solutions at physiological temperature and pH. The electrochemical characterization was also preliminary investigated as function of surface wettability of titania surfaces. TiO2 thin films demonstrated a non-faradaic range and a cathodic threshold voltage, which were suitable for an implantable electrode, together with high dielectric constant, k, of primary importance for capacitive communication devices. Electrophysiological studies, through patch-clamp protocol, demonstrated a great action potentials and activity passive properties, like resting potential (Vresting), much closer to physiological values for neurons on UV-exposed TiO2 deposits. The investigated neuron passive properties differ greatly in relation to the presence or absence of the UV exposure, showing a difference in the maturation of the neurons, characterized by an enhanced neuronal compatibility on UV treated-TiO2 surfaces.