We present a novel concept for cuff electrodes that greatly simplifies the insertion procedure on nerves as small as 100 µm. Cuff electrodes serve as peripheral nerve interfaces for neural stimulation or recording, with various applications including chronic pain management, sleep apnea treatment, and high blood pressure control. Existing methods for securing cuff electrodes on larger nerves in the millimeter range rely on surgical threading, zip tie-like closing mechanisms, or prefolded spiral cuff geometries. While these approaches are effective for larger nerves containing multiple fibers branching out to different target regions, they present challenges when targeting smaller nerves with diameters of 100 µm or below. The fragility of such nerves and the difficulties in handling small probes make interfacing with typical cuff electrode systems a challenging task.

To overcome these challenges, our approach leverages 3D and 4D printing techniques, in combination with flexible and superabsorbent materials. These materials readily conform to the shape of the nerve upon contact with body fluid, allowing the electrodes to wrap around the nerve without requiring manual deformation [1]. This approach reduces the risk of nerve damage during implantation. Notably, we have successfully implanted these devices in a locust model and demonstrated their efficacy in recording and stimulating neural activity as well as associated muscle activation. The geometric design of our cuff electrodes features electrodes distributed along both the axial and circumferential directions, enabling enhanced spatially selective sensing and stimulation capabilities.

In summary, our nerve cuff electrode concept offers a transformative solution for the implantation of electrodes on ultra-small nerves, streamlining the procedure and minimizing potential harm. Through the utilization of state-of-the-art rapid fabrication techniques and adaptable materials, we have developed a simple procedure for recording and stimulating of neural activity. The incorporation of electrodes distributed along multiple directions further enhances the potential for selective sensing and stimulation.

Biomaterial scaffolds have emerged as a tool to build 3D cultures of cells which better resemble biological systems, while advancements in bioelectronics have enabled the modulation of cell proliferation, differentiation, and migration.

Here, we first describe a porous conductive hydrogel with the same mechanical modulus and viscoelasticity as neural tissue. Electrical conductivity is achieved by incorporating low amounts (<0.3% weight) of carbon nanomaterials in an alginate hydrogel matrix, and then freeze-drying to self-organize into highly porous networks. The mechanical and electrical properties of the material can be carefully tuned and used to modulate the growth and differentiation of neural progenitor cells (NPCs). With increasing hydrogel viscoelasticity and conductivity, we observe the formation of denser neurite networks and a higher degree of myelination.

To investigate the functionality of neurite networks in 3D, we begin by placing a polydimethylsiloxane (PDMS) microstructure on an underlying multielectrode array (MEA). We then explore different materials and techniques to integrate hydrogels into the PDMS microstructures, such that the hydrogel can facilitate neurons to form 3D networks while still confined by the PDMS. This platform can be used to support the growth of human iPSC-derived sensory neurons, with and without a co-culture of human Schwann cells. Additionally, our platform is compatible with various methods to assess neuronal functionality (e.g. MEA electrical recordings), and can be used to understand the effect(s) of hydrogel properties on the resulting neuronal networks. Both described biomaterial systems can support the growth of neuronal cells for over 12 weeks to investigate neuronal development and disease progression. Further, we have demonstrated the use of these materials for the fabrication of implantable surface electrode arrays which can seamlessly interface with electrically active tissues such as the brain and heart.

Bioelectronic medicine have enormous potential not only to replace lost body function but also for guiding and encouraging regenerative processes, helping the body to self-repair. The ability of our skin to self-heal is something so integral to our everyday life that we barely reflect on how remarkable this is. Other parts of our bodies have very limited healing capability, especially the very complex structures of brain and spinal cord. Furthermore, while most of us take our self-repairing skin for granted, old age and certain diseases can drastically reduce this ability, greatly increasing the risk that seemingly uncomplicated wounds develop into chronic ones.  

Together wiht my team I have shown how electrical field stimulation can have a guiding effect on skin cell migration, which could be of great significance to speed up wound closure and reduce the risk for chronic wounds. Together with collaboration partners we now explore how similar principles can be used to promote more constructive repair after traumatic injury. The common denominator for these therapeutic concepts is electrical field stimulation, in other words direct current injected into the tissue. This places special constraints on the electrode materials used to ensure biocompatible and reversible direct current injection mechanisms. My talk will outline some material concepts that we have developed for this and which electrochemical boundary conditions that apply to ensure that direct current stimulation can be sustained in tissue even with fully implantable systems. I will showcase how we employ conducting polymer hydrogels for direct current stimulation, and how such technology allows for new discoveries as well as potential future therapies.

From extracellular matrices (ECM) in connective tissues, to silks spun by spiders, and textile fibers weaved in fabrics, small diameter fibers widely exist in nature and have been closely associated with our daily life. These individual fibers have quasi-one-dimensional flexible structures, with diameters smaller than ~100 µm, and length to width aspect ratios greater than ~100. Orderly assembling fibers into arrays and three-dimensional architectures with designable chemical properties and sensing capabilities could open a range of bioelectronics and biointerface applications. In this presentation, I will demonstrate biofabrication and fiber printing techniques that enable the patterning of functional fiber architectures in three dimensions. These fiber printing techniques extend the materials libraries and device designs, which underpin technological capabilities from enabling fundamental studies in cell migration, to customizable and eco-friendly fabrication of wearable sensors. Finally, I will provide an outlook on the strategic pathways for developing next-generation bioelectronics using fibers as architectural building blocks.

Use of light for selective and spatio-temporally resolved control of cell functions (photoceutics) is emerging as a valuable alternative to standard electrical and chemical methods. Here, we propose the use of smart materials, and in particular of organic semiconductors, as efficient and biocompatible optical transducers in the field of regenerative medicine.

Devices able to selectively and precisely modulate the fate of living cells, from adhesion to proliferation, from differentiation up to specific function, upon visible light will be presented. Examples of practical applications, recently reported by our group, include optical modulation of the activity of both excitable and non-excitable cells, control of essential cellular switches like transient receptor potential channels and other cationic channels, as well as effective modulation of intracellular calcium signaling for precise control of cell metabolic processes. We describe fabrication and optimization of micro- and nano-structured polymeric interfaces, in the form of beads and 3D scaffolds, with different cell models. As representative examples, we report on (i) functional interaction with intracellular proteins, leading to non-toxic modulation of the cell redox balance [1,2]; (ii) a novel strategy to gain optical control of Endothelial Progenitor Cell (EPC) fate and to optically induce angiogenesis in vitro [3]; (iii) optical modulation of mesenchymal stem cells and human-induced pluripotent stem cells physiological pathways [4]; (iv) effects of light-sensitive 3D scaffolds on neurogenesis [5]. Current knowledge about the photo-activated processes occurring at the conjugated polymer/living cell interface, obtained by complementing several physical/chemical/biological characterization techniques, is also critically discussed.  The above mentioned study-cases represent, to the best of our knowledge, first reports on use of organic semiconductors for optical modulation of the cell fate, with disruptive perspectives in cell-based therapies. Future opportunities and perspective applications in regenerative medicine will be critically evaluated in the conclusions.

Photovoltaic implants introduce a new wireless method for precise electrical stimulation of tissue using the conversion of light into electrical energy, employing thin layers of organic semiconductors on a flexible substrate. With their remarkable potential for biomedical applications, these implants offer a versatile platform capable of delivering targeted electrical stimuli in the brain, facilitating the development of neuronal networks, and fostering regeneration and neuroprotection following traumatic brain injury [1]. Applications include devices that can be placed on the surface of the brain, or in the form of cuffs wrapped around nerves, which have already been showcased in numerous studies [2,3].

However, these principles may be applied in many other areas. They hold promise for use in electrical nerve conduits. By simultaneously providing guidance and stimulation to regenerating nerves, these conduits can help promote axonal regrowth, reconnection, and functional recovery. The precise control over electrical parameters through light enables tailored interventions, allowing for targeted treatment strategies in cases of nerve damage, peripheral neuropathies, or even spinal cord injuries [4]. On the other hand, the use of optoelectronic devices as capacitive sensors opens up avenues for monitoring tissue properties, neuronal activity and nerve growth, and for investigating brain-diseases in both research and clinical settings.

Our studies emphasize general essential requirements for these different clinical applications. Notably, our focus lies on fabrication methods of new devices, biocompatibility, the distribution of the electric field in biological tissue, and their ability to influence cellular growth.

To assess biocompatibility, Chick Chorioallantoic Membrane (CAM) assays were conducted and tissue was sampled for immunohistochemical studies. Furthermore, colorimetric LDH cytotoxicity assays were used to quantify possible adverse effects of the devices when in contact with primary cell cultures of cortical neurons [5].

In addition to quantifying the biocompatibility of these photovoltaic implants, investigating their generated electric field and long-term stability is imperative to optimize their performance. Therefore, a custom measurement system was employed to characterize the spatial distribution of the electric field in an aqueous solution during stimulation over the span of several hours to several days. By precisely mapping the electric field, we gained insights into the long-term stability of the device, and efficacy and intensity of the stimulation to optimize precise targeting of specific areas with low light intensities while minimizing potential damage to the surrounding tissue.

Furthermore, we utilized in vitro experiments to observe the effects of photovoltaic stimulation on the intrinsic electrical activity, signal transmission and morphology of neuronal cell cultures. Voltage-sensitive dyes provide real-time feedback on the neuronal response to optoelectronic stimulation. Long-term observations of morphological changes using a microscopy setup were used to investigate the phenomenon of electrotropism to give insights into directional cell growth patterns and structural alterations in response to electrical stimulation, to further support the potential of these electrodes to guide and manipulate cellular growth [6].

Through our studies encompassing biocompatibility assessments, electric field mapping, and in vitro experiments, we aim to optimize fabrication steps, increase their performance and promoting research on optoelectronics in biomedical engineering.

All throughout life, from early embryonic development through the operation and interaction of cells and tissues in the adult body up to the process of regeneration, biophysical signals, particularly mechanosensation, play a crucial role. Extracellular mechanical stimuli cause tissue regeneration, which includes processes including cell division, differentiation, migration, and ejection [1,2,3]. Age causes the body's ability to rejuvenate to decline, which negatively impacts on our lives.

The techniques for modulating or controlling mechanical stimulation of cells that are currently available frequently lack the effectiveness, dependability, reversibility, and spatial sensitivity needed for in vitro and in vivo applications. Here, we demonstrate a cutting-edge method for manipulating mechanosensitive ion channels using exogenous organic semiconductors. Materials of this class may be readily processed into a variety of forms, such as thin films, microstructured devices, or nanoparticles, and are totally biocompatible, providing the potential for in vivo use. However, their particular opto-electrical characteristics stand out the most, offering exceptional visible light responsivity as well as electron and ion conductivity.

In this study, we investigate the potential for accurate and efficient regulation of the activation of mechanosensitive ion channels using organic semiconductors, particularly conjugated polymers. We critically examine the outcomes produced by various techniques, such as microstructured devices and polymer thin films.

Our findings may pave the way for the development of cutting-edge smart materials for tissue regeneration triggered by physical stimuli.

An organic photoelectrochemical transistor (OPECT) is an organic electrochemical transistor (OECT), where the output current is controlled by light. OPECT has promising performance in biosensing with transconductance improved up to the physical limit, enhancing sensor sensitivity. However, to render an OECT photosensitive, photoactive materials should be integrated into the device, relying on additional metals, sophisticated nanostructures, and tedious synthetic approaches. This study developed an all-in-one OPECT structure, where a single photosensitive polymeric mixed ionic-electronic conductor was used as the photoactive gate and the channel material. A range of n-type polymeric mixed conductors was studied to understand the material requirements. The OPECT performance was investigated by evaluating the photoelectrochemical characteristics in electrode configuration and inherent OECT properties in dark conditions. We find that the photovoltage induced by light mainly controls the OECT output, the extent of which is controlled by the lifetime of photoinduced species. Using photosensitive polymers with long exciton lifetimes is key to maximizing OPECTs performance for light-gated bioelectronic devices.

The field of Bioelectronics aims to integrate electronics and biology, offering promising opportunities in various domains. However, a major hurdle in this field is the mechanical mismatch between rigid electronics and the soft nature of living tissues. Bioelectronic devices based on soft and flexible materials, developed by using microfabrication and printing techniques, aim to bridge the mismatch between the two worlds. In contrast, biological processes polymerize small molecules to create intricate micromachines. Inspired by biology, we utilize enzymatic processes and thiophene-based oligomer building blocks to in vivo generate organic conductors. By harnessing the advantages of this approach, we successfully achieved the in-situ formation of conducting polymer gels within living organisms. These gels exhibited soft mechanical properties that closely resemble those of natural tissues. Furthermore, we demonstrated the enzymatic construction of organic conductors in various tissues and their application as active materials in organic transistors. Our alternative approach overcomes the limitations of conventional methods, providing opportunities for the development of novel, soft, and bio-compatible electronic interfaces. This paradigm shift in the development of organic bioelectronics opens avenues for healthcare, bioengineering, and beyond.

2D MXenes exhibit a range of interesting properties that make them suitable for healthcare-related applications. These include efficient electronic and ionic charge transport, hydrophilicity, redox activity, biocompatibility, antimicrobial effects, vis-NIR plasmon resonance, photothermal effect (light to heat conversion), tunable surface terminal groups, and structural and chemical tunability.  In addition, MXenes can be synthesized using solution processing in water providing a simple method for low-cost processing of 2D flakes, thin and thick films, aerogels, and hydrogels at scale. Recently, the applications of MXene in healthcare and biomedical applications have seen tremendous activity covering areas such as biosensing, electrophysiology, tissue engineering, antimicrobial and antiviral treatments, and therapeutics.

In this talk, I will discuss the use of MXenes in several devices for biomedical applications. This includes using MXene-based hydrogels as physical and electromechanical sensors (e.g., physical motion, body artifacts, muscle fatigue) including wearable and stand-alone sensors.  The talk will also cover using MXene-based composites as wearable sweat sensors with a unique modular design that enabled a simple exchange of the specific sensing electrode to tailor to the desired analytes to detect multiple biomarkers in sweat. The talk also includes leveraging the ability of MXene hydrogels to absorb ultrasound energy to develop an implantable battery that can be charged remotely from medical ultrasound probes. Promising new directions for MXenes and related composition will be discussed.

Our understanding of the brain and general neural systems is based on models of increasing complexity, from 2D cell culture to organoids and organotypic slices to animal models. These models provide significant insight into neuronal information processing in the brain, but require advanced electrophysiological measurement technologies to achieve long-term stable recordings with single-cell and millisecond space-time resolution. Thus, challenges remain to study information processing between neurons with high spatiotemporal resolution and high signal-to-noise ratio (SNR). These challenges are overcome by well-established planar multichannel devices, but at the expense of signal-to-noise ratio. Without sufficient electrode-cell coupling, planar microelectrode arrays (MEAs) provide low-amplitude signals that are difficult to correctly assign by spike sorting algorithms. Furthermore, the unresolved subthreshold signals lose valuable information that is essential for direct estimation of synaptic weights and correct generation of connectivity matrices in neural networks.

To yield better cell-electrode coupling, numerous vertical nanostructures and nanoelectrodes have been developed by several groups. Here we present the concept of nanocavity (NC) MEAs with vertical nanostraws. High aspect ratio nanostraws (NS) were engineered to initiate tight cell-structure coupling, while the nanocavity reduces the electrode impedance. This combination yields a spontaneous tight mechanical coupling and results in long-term recordings with increased signal amplitude, with no poration-inducing external forces or surface functionalization [1]. Moreover, simultaneous patch-clamp and MEA recordings of the coupled neuron directly demonstrated the capability of our device to record post-synaptic potentials. Here we show that PSP resolution persisted throughout the measurements, indicating a stable and long-term subthreshold amplitude sensitivity.

Simultaneous electrical recordings with good spatial and temporal resolution from 3D neuronal structures (organoids or organotypical slices) is also technological limited. Here we present our recent developments to overcome this limitations by 3D MEA which allow the recording from inside the neuronal tissue [Shihada et al, submitted].

Understanding and modulating neural networks requires high-resolution acquisition of neural activity over time, real-time analysis, and minimally invasive stimulation methods with high specificity. Such procedures are particularly needed for treatment of sensory disfunction (e.g. hearing loss), and certain neurological diseases (e.g. epilepsy). The lack of soft, biocompatible, hybrid and smart neural interfaces hinders our capacity to study complex neural dynamics and efficiently apply responsive neuromodulation therapy. Here, I am presenting the vision of Neural Waves lab towards designing and developing materials and novel fully implantable, contained and responsive neural interfaces that will allow long-term acquisition and closed-loop manipulation of neural circuits with high spatiotemporal resolution over extended period of time to reveal neural dynamics in different neurological pathways and alleviate disfunctions and diseases. I will cover our studies on i) creating artificial basilar membrane based on acousto-sensitive ion-based transistors and soft electronics, ii) innovating electroencephalography interfaces, and iii) utilizing organic perforated multielectrode arrays to investigate the effect of photopharmacological interventions on Cortical Seizures.

Minimally-invasive neuromodulation using low-intensity focused ultrasound (LIFU) holds great promise for treating various neurological disorders. It has been demonstrated to modulate neural activity, promoting both excitatory and inhibitory effects. This capability allows for restoring aberrant neural circuitry or suppressing hyperactive regions, thereby alleviating symptoms associated with conditions such as Parkinson's disease, epilepsy, chronic pain, and depression.

One of the key advantages of LIFU neuromodulation is its combination of high spatial resolution, minimal invasiveness, and extensive coverage of the nervous system. Unlike traditional electrical, magnetic, or optical neuromodulation techniques, which can achieve high-spatial resolution at the expense of high invasiveness and reduced brain coverage, ultrasound waves benefit from low wavelengths, scattering, and absorption in brain tissue and hence, can be focused virtually anywhere in the brain, with high-spatial-resolution and without requiring brain surgery. This reduces the risk of infection, tissue damage, and other complications associated with invasive procedures, making it a safer option for patients, and also allows for accessing a broader range of neural circuits with high precision.

Despite the abovementioned promise, there is still a knowledge and technological gap in LIFU neuromodulation to maximize its potential. LIFU neuromodulation is achieved by means of an ultrasound transducer. These transducers generate low-intensity focused ultrasound waves that can penetrate deep into tissues while maintaining spatial specificity. By adjusting the parameters of the ultrasound waves, specific regions of the brain or peripheral nerves can be targeted with precision. However, similar to their use in medical diagnostic imaging, conventional ultrasound transducers used in LIFU neuromodulation have hand-held form factors and require off-the-shelf equipment. These bulky setups lead to two severe limitations:  in pre-clinical research, the mismatch of size between bulky transducers and in-vitro/in vivo models (mice, rats) impose severe limitations in understanding the effects of ultrasound on the nervous system and how to better apply LIFU neuromodulation for different disease models; secondly, in clinical applications, the use of LIFU neuromodulation can only be applied in a bed-side scenario, where the patient either would visit the clinic once or twice per week to receive a treatment or would operate a LIFU neuromodulation system at home.

This talk will describe the recent research in the field of ultrasound microsystems towards developing the next generation of LIFU neuromodulation systems that can be seamlessly integrated into in vitro/in vivo experimental setups in pre-clinical settings and used as wearable and minimally-invasive devices for clinical treatments. This description will answer two questions: how to massively integrate all the necessary LIFU neuromodulation functionality into a single-miniaturized and battery-powered microsystem? How can ultrasound microsystems be designed to be mechanically flexible to better adjust to the body's natural curvature?

To answer these questions, the talk will focus on novel ultrasound microfabrication and microsystem integration methods and the next-generation ultrasound electronics, while showing a few examples of ongoing projects featuring in vitro and in vivo validation showcasing the potential of LIFU microsystems for minally invasive and precise neuromodulation for the treatment of neurological diseases.

The effectiveness of many chemotherapeutic agents in treating cancer is limited by poor delivery efficiency and systemic toxicity. Local chemotherapy approaches utilizing iontronic devices present a promising solution for efficient interference with cancer growth and tumor size reduction. We use iontronic devices with incorporated membranes to enable the continuous delivery of chemotherapeutics with high spatiotemporal resolution. We operate freestanding iontronic pumps with the the chemotherapeutics Gemcitabe (Gem) named GemIPs to treat a GBM model on the chicken chorioallantoic membrane. In addition, we compare results with a conventional topical daily treatment. We see that both administration techniques induce G2-phase cell cycle arrest and apoptosis. Remarkably, growth inhibition was achieved only with the steady Gem dosing with GemIPs, but not with daily topical drug administration at the maximum dosage amounts that was not lethal for the chick embryo. I will discuss how the different transient concentration profiles between the techniques generates this difference in outcome. 

The generation of in vitro platforms capable of mimicking the in vivo situation as an alternative to animal models and/or monitoring cellular processes is necessary for medicine and drug discovery [1]. In this sense, Smart Bioelectronics arise from the combination of smart functional materials, bioelectronics and microfluidics, making Smart Bioelectronics a powerful tool to control cellular microenvironments.

Smart functional materials such as poly(N-isopropylacrylamide) (pNIPAAm) can undergo structural changes due to their inherent lower critical solution temperature (LCST) phase transition in water at 32 ºC. On its side, poly(3,4-ethylenedioxythiopene):poly(styrene sulfonate) (PEDOT:PSS) is a widely used conducting polymer in the bioelectronics field, due to its mixed ionic and electronic conduction properties. When mixing both polymers, the developed PEDOT:PSS/pNIPAAm co-polymer modulates cellular adhesion/detachment of cancer cells and the electrochemical monitoring of the process [2-3].

Moreover, PEDOT can be tailored biochemically and mechanically to replicate a specific tissue. PEDOT polymers made in combination with biopolymers and glycosaminoglycans such as collagen and hyaluronic acid can be used in the generation of 3D bioelectronic interfaces with physiologically relevant conditions [4-5]. On the other hand, microfluidic devices offer optical transparency, miniaturization, and controlled media perfusion required in organ-on-a-chip models. The interface between 3D bioelectronics and microfluidic devices enables the real-time electrical and optical monitoring of cellular processes in a controlled microenvironment.

Here, we present an overview of different 2D and 3D Smart Bioelectronic interfaces for the simultaneous electrical and optical monitoring of cancer cell migration.

Research on electrolyte-gated and organic electrochemical transistor (OECT) architectures is motivated by the prospect of a highly biocompatible interface capable of amplifying bioelectronic signals at the site of detection. Despite many demonstrations in these directions, a quantitative model for OECTs as impedance biosensors is still lacking. We overcome this issue by introducing a model experiment where we simulate the detection of a single cell by the impedance sensing of a dielectric microparticle. The highly reproducible experiment allows us to study the impact of transistor geometry and operation conditions on device sensitivity. With the data we rationalize a mathematical model that provides clear guidelines for the optimization of OECTs as single cell sensors, and we verify the quantitative predictions in an in-vitro experiment. In the optimized geometry, the OECT-based impedance sensor allows to record single cell adhesion and detachment transients,  showing a maximum gain of 20.2±0.9 dB with respect to a single electrode-based impedance sensor.

The common methods for in-vivo delivery of biomolecules  are strongly limited by invasiveness and/or lack of quantitative delivery control. These limitations can be overcome by the Organic Electronic Ion Pump (OEIP), that electrophoretically delivers ions without fluid flow and ions backflow from tissue, enabling quantitative studies. The capillary-based OEIPs have been demonstrated to be minimally invasive, however, the micro-scale glass capillaries are brittle, thus tend to break during insertion in harder tissues. In this work, we developed flexible and robust OEIPs based on polyimide-coated glass capillaries, enabling their insertion in a wide range of biological tissues. We provide evidence that sufficient intensity of blue light penetrates via the polyimide coating, although it is commonly accepted that polyimide’ high optical absorption prevents polymerization using high energy light. Using low cost, water soluble photoinitiators and blue light, we established a cheap and environmentally safe system for photo-crosslinking via polyimide coating.

The resulting OEIP devices can reliably deliver abscisic acid (ABA), the so-called plant stress hormone, one of the most challenging substances delivered using iontronic devices. The developed OEIP was applied to deliver ABA directly into the petiole of intact Arabidopsis leaves, establishing an advanced petiole feeding tool. In contrary to the conventional petiole feeding assays, OEIP enables ion delivery to intact plants with a high control of the delivered dose and elimination of the disturbances induced by convective delivery. By delivering ABA to the petiole, we triggered immediate and long-lasting stomata closure, without observable wound effect, demonstrating the high potential of the developed bioactuator. The mechanism of the induced stomata closure was studied by delivering endogenously absent deuterium-labeled ABA, confirming that the closure was induced by the delivered ABA ions that were distributed to the leaf blade by the plant vasculature.

Bacterial infections are one of the major threats to public health, food safety and development which makes it is necessary develop materials and strategies that limit or prevent these bacterial proliferations and biofilm infections.[1] Although, medical implants have led to dramatic improvement in patient's health and well-being, they are accompanied by drawbacks that include surgical risks during placement or removal, implant failure and more specifically microbial infections. These implant-associated infections are mainly caused by the bacterial bio-films in which bacteria are more recalcitrant towards treatments. Indeed, implant surfaces are non-vascularized abiotic materials rendering the common strategies inappropriate and ineffective.[2] In this context we have designed and developed innovative and smart interfaces based on phosphonium self-assembled monolayers (SAMs)  that can be electrically activated on-demand for eradicating bacterial infections on solid surfaces. Hence, upon electroactivation, a successful eradication of gram-positive and gram-negative bacterial strains has been clearly highlighted on SAM-modified titanium surfaces. Subsequently, we observed 95% and 90% antibacterial efficiencies against Staphylococcus aureus and Klebsiella pneumoniae. More importantly, no cytotoxicity has been observed towards eukaryotic cells which clearly demonstrates the biocompatible character of these novel surfaces for further implementation.

Additionally, in our ongoing work, we have explored the synergistic relationship between electrical stimulus for drug delivery and wound healing. Our bodies naturally generate endogenous electrical fields in order to facilitate the migration of fibroblasts, keratinocytes, macrophages, epithelial cells and ions to the wound site to speed up the healing process.[3] In this regard, we have designed and developed electrochemically polymerized polypyrrole films deposited on ITO substrates encapsulated with antimicrobial peptides, which can be released in a controlled manner upon electrical application. Apart from exploring the phenomenon of electrotaxis in wound healing as a consequence of applying an exogenous electrical field, the bioelectric effect is also being studied in depth to understand the mechanisms by which applied electrical fields render the surface antimicrobial. We highlight the advantages of using electrochemical deposition as a technique for film formation as it allows for precise control over film thickness, surface roughness and homogeneity, and can expand the application for these films to not only as electrically responsive wound healing patches, but also as coatings for food packaging and other wearable electronics. These films have been characterized and their properties have been thoroughly studied using various techniques which further support the successful antimicrobial encapsulation throughout its internal framework. Finally, the biocompatible nature of these films supports their potential in various applications.

1.Tacconelli, E.; Carrara, E.; Savoldi, A.; Harbarth, S.; Mendelson, M.; Monnet, D. L.; Pulcini, C.; Kahlmeter, G.; Kluyt-mans, J.; Carmeli, Y.; Ouellette, M.; Out-terson, K.; Patel, J.; Cavaleri, M.; Cox, E. M.; Houchens, C. R.; Grayson, M. L.; Hansen, P.; Singh, N.; Theuretzbacher, U.; Magrini, N. (2018) Lancet Infect. Dis.18, 318-327.

2. Carrara, S.; Rouvier, F.; Auditto, S.; Brunel, F.; Jeanneau, C.; Camplo, M.; Sergent, M.; About, I.; Bolla, J.-M.; Raimundo, J.-M. Int. J. Mol. Sci. 2022, 23, 2183. https://doi.org/10.3390/ijms23042183

3. Farber, P. L., Isoldi, F. C., & Ferreira, L. M. (2021). Electric Factors in Wound Healing. Advances in wound care, 10(8), 461–476. https://doi.org/10.1089/wound.2019.1114