Laura Anne Poole-Warren

Hydrogel coatings provide a promising pathway to tailor and improve cell culture surfaces, maintaining bulk material properties desired for handling and optical measurement while providing cell–surface interactions vital for optimising cell behaviour. For immobilised hydrogels to be useful, layers of this structure must be robustly adhered to the substrate and able to withstand strain from sources such as tensile forces exerted by adherent cell lines and fluid streams in microfluidic devices. Plasma‐activated coatings (PAC) are investigated here as a method for robust and translatable hydrogel immobilisation. Results show that embedded radicals within the PAC can immobilise methacrylated poly‐vinyl alcohol hydrogels, forming nanometer‐thick (reagent‐free) to millimeter‐thick (photoinitiator‐assisted) hydrogel layers. Utilisation of the nanometer reagent‐free layer as a ‘primer layer’ before forming photoinitiator‐assisted millimeter‐thick layers is a novel approach that results in superior adhesion of the thicker gel layers. When used as a cell culture surface for MCF‐7 cells, E cadherin and vinculin signalling significantly ( p < 0.05) increased (for physiologically relevant High MA hydrogel compared to the glass control). This work therefore outlines the novel reagent‐free primer layer approach as a method for creating hydrogels with superior adhesion for in vitro culture of cells.

Objective . This study evaluated electrochemical and biological factors governing Pt dissolution in neural prosthetic electrodes. Implantable neuromodulation devices rely on platinum (Pt) electrodes for safe and effective operation. However, accumulating evidence shows that Pt electrodes can corrode and release ionic and particulate Pt material into the environment. This dissolution behaviour can impair device performance and introduces unresolved biocompatibility concerns, since its mechanistic drivers in biologically relevant environments remain poorly defined. Approach. Using biphasic charge-balanced pulses delivered over acute and subchronic one-week intervals, the effects of charge density, frequency, and cumulative charge were decoupled while quantifying dissolution in the presence of proteins, and fibrotic-tissue mimics. Main results . Charge density emerged as the dominant determinant, explaining ∼86% of dissolution variability, whereas frequency and aggregate charge exerted weaker but significant influences. Acute pulse produced highly variable Pt release linked to removal of loosely bound material, whereas subchronic dissolution reflected more uniform electrochemical degradation. Protein-model solutions reduced Pt loss by 2–5×, and fibrotic-tissue mimics suppressed release by up to two orders of magnitude. Although these interfaces increased impedance and altered charge-storage behaviour, electrochemical metrics alone did not predict dissolution, indicating that biological interfaces function primarily as physicochemical barriers. New quantification strategies revealed that particulate Pt dominated acute degradation (⩾68%), whereas ionic species were more prevalent subchronically. Conventional inductively coupled plasma mass spectrometry underestimated total Pt by 66%–99% in particulate-rich samples. Significance . These findings reconcile longstanding inconsistencies in the literature and stress the need of distinguishing ionic from particulate Pt when evaluating cytotoxicity, electrode longevity, and the long-term safety of neural interfaces.

Minimal PLL integration (0.002 wt%) in PVA hydrogels, via physical or covalent crosslinking, improved laminin retention, motor neuron progenitor adhesion and neurite growth without cytotoxicity or loss of hydrogel stability.

Integration of bioelectronic devices in clinical practice is expanding rapidly, focusing on conditions ranging from sensory to neurological and mental health disorders. While platinum (Pt) electrodes in neuromodulation devices such as cochlear implants and deep brain stimulators have shown promising results, challenges still affect their long‐term performance. Key among these are electrode and device longevity in vivo, and formation of encapsulating fibrous tissue. To overcome these challenges, organic conductors with unique chemical and physical properties are being explored. They hold great promise as coatings for neural interfaces, offering more rapid regulatory pathways and clinical implementation than standalone bioelectronics. This study provides a comprehensive review of the potential benefits of organic coatings in neuromodulation electrodes and the challenges that limit their effective integration into existing devices. It discusses issues related to metallic electrode use and introduces physical, electrical, and biological properties of organic coatings applied in neuromodulation. Furthermore, previously reported challenges related to organic coating stability, durability, manufacturing, and biocompatibility are thoroughly reviewed and proposed coating adhesion mechanisms are summarized. Understanding organic coating properties, modifications, and current challenges of organic coatings in clinical and industrial settings is expected to provide valuable insights for their future development and integration into organic bioelectronics.

Optical-electrode (optrode) arrays use light to modulate excitable biological tissues and/or transduce bioelectrical signals into the optical domain. Light offers several advantages over electrical wiring, including the ability to encode multiple data channels within a single beam. This approach is at the forefront of innovation aimed at increasing spatial resolution and channel count in multichannel electrophysiology systems. This review presents an overview of devices and material systems that utilize light for electrophysiology recording and stimulation. The work focuses on the current and emerging methods and their applications, and provides a detailed discussion of the design and fabrication of flexible arrayed devices. Optrode arrays feature components non-existent in conventional multi-electrode arrays, such as waveguides, optical circuitry, light-emitting diodes, and optoelectronic and light-sensitive functional materials, packaged in planar, penetrating, or endoscopic forms. Often these are combined with dielectric and conductive structures and, less frequently, with multi-functional sensors. While creating flexible optrode arrays is feasible and necessary to minimize tissue–device mechanical mismatch, key factors must be considered for regulatory approval and clinical use. These include the biocompatibility of optical and photonic components. Additionally, material selection should match the operating wavelength of the specific electrophysiology application, minimizing light scattering and optical losses under physiologically induced stresses and strains. Flexible and soft variants of traditionally rigid photonic circuitry for passive optical multiplexing should be developed to advance the field. We evaluate fabrication techniques against these requirements. We foresee a future whereby established telecommunications techniques are engineered into flexible optrode arrays to enable unprecedented large-scale high-resolution electrophysiology systems.

Recording and monitoring electrically-excitable cells is critical to understanding the complex cellular networking within organs as well as the processes underlying many electro-physiological pathologies. Biopotential recording using an optical-electrode (optrode) is a novel approach which has potential to significantly improve interface-instrumentation impedance mismatching as recording contact-sizes become smaller and smaller. Optrodes incorporate a conductive interface that can sense extracellular potential and an underlying layer of liquid crystals that passively transduces electrical signals into measurable optical signals. This study investigates the impedance properties of this optical technology by varying the diameter of recording sites and observing the corresponding changes in the impedance values. The results show that the liquid crystals in this optrode platform exhibit input impedance values (1 MΩ – 100 GΩ) that are three orders of magnitude higher than the corresponding interface impedance, which is appropriate for voltage sensing. The automatic scaling of the input impedance enabled within the optrode system maintains a relatively constant ratio between input and total system impedance of about one for sensing areas with diameters ranging from 40 µ m to 1 mm, at which the calculated signal loss is predicted to be <1%. This feature preserves the interface-transducer impedance ratio, regardless of the size of the recording site, allowing development of passive optrode arrays capable of very high spatial-resolution recordings.

Active implantable neurological devices like deep brain stimulators have been used over the past few decades to treat movement disorders such as those in people with Parkinson’s disease and more recently, in psychiatric conditions like obsessive compulsive disorder. Electrode-tissue interfaces that support safe and effective targeting of specific brain regions are critical to success of these devices. Development of directional electrodes that activate smaller volumes of brain tissue requires electrodes to operate safely with higher charge densities. Coatings such as conductive hydrogels (CHs) provide lower impedances and higher charge injection limits (CILs) than standard platinum electrodes and support safer application of smaller electrode sizes. The aim of this study was to examine the chronic in vivo performance of a new low swelling CH coating that supports higher safe charge densities than traditional platinum electrodes. A range of hydrogel blends were engineered and their swelling and electrical performance compared. Electrochemical performance and stability of high and low swelling formulations were compared during insertion into a model brain in vitro and the formulation with lower swelling characteristics was chosen for the in vivo study. CH-coated or uncoated Pt electrode arrays were implanted into the brains of 14 rats, and their electrochemical performance was tested weekly for 8 weeks. Tissue response and neural survival was assessed histologically following electrode array removal. CH coating resulted in significantly lower voltage transient impedance, higher CIL, lower electrochemical impedance spectroscopy, and higher charge storage capacity compared to uncoated Pt electrodes in vivo, and this advantage was maintained over the 8-week implantation. There was no significant difference in evoked potential thresholds, signal-to-noise ratio, tissue response or neural survival between CH-coated and uncoated Pt groups. The significant electrochemical advantage and stability of CH coating in the brain supports the suitability of this coating technology for future development of smaller, higher fidelity electrode arrays with higher charge density requirement.

Fabrication of three-dimensional (3D) constructs to model body tissues and organs can contribute to research into tissue development and models for studying disease, as well as supporting preclinical drug screening in vitro. Furthermore, 3D constructs can also be used for diagnosis and therapy of disease conditions via lab on a chip and microarrays for diagnosis and engineered products for tissue repair, replacement, and regeneration. While cell culture approaches for studying tissue development and disease in two dimensions are long-established, the translation of this knowledge into 3D environments remains a fertile field of research. In this Tutorial, we specifically focus on the application of biosynthetic hydrogels for neural cell encapsulation. The Tutorial briefly covers background on using biosynthetic hydrogels for cell encapsulation, as well as common fabrication techniques. The Methods section focuses on the hydrogel design and characterization, highlighting key elements and tips for more effective approaches. Coencapsulation of different cell types, and the challenges associated with different growth and maintenance requirements, is the main focus of this Tutorial. Much care is needed to blend different cell types, and this Tutorial provides tips and insights that have proven successful for 3D coculture in biosynthetic hydrogels.

Objective: This study evaluated subthreshold biphasic stimulation pulses as a strategy to stabilize electrode impedance via control of protein adsorption. Following implantation, cochlear electrodes undergo impedance fluctuations thought to be caused by protein adsorption and/or inflammatory responses. Impedance increases can impact device power consumption, safe charge injection limits, and long-term stability of electrodes. Methods: Protein-mediated changes in polarization impedance (Zp) were measured by voltage transient responses to biphasic current pulses and electrochemical impedance spectroscopy, with and without protein solutions. Four subthreshold stimulation regimes were studied to assess their effects on protein adsorption and impedance; (1) symmetric charge-balanced pulses delivered continuously, (2) at 10% duty cycle, (3) at 1% duty cycle, and (4) an asymmetric charge balanced pulse delivered continuously with a cathodic phase twice as long as the anodic phase. Results: The Zp of electrodes incubated in protein solutions without stimulation for 2 hours increased by between ~28% and ~55%. Subthreshold stimulation reduced the rate at which impedance increased following exposure to all protein solutions. Decreases in Zp were dependent on the type of protein solution and the stimulation regime. Subthreshold stimulation pulses were more effective when delivered continuously compared to 1% and 10% duty cycles. Conclusion: These results support the potential of subthreshold stimulation pulses to mitigate protein-mediated increase in impedance. Significance: This research highlights the potential of clinically translatable stimulation pulses to mitigate perilymph protein adsorption on cochlear electrodes, a key phenomenon precursor of the inflammatory response.