Electric field bridging-effect in electrified microfibrils' scaffolds.

Introduction: The use of biocompatible scaffolds combined with the implantation of neural stem cells, is increasingly being investigated to promote the regeneration of damaged neural tissue, for instance, after a Spinal Cord Injury (SCI). In particular, aligned Polylactic Acid (PLA) microfibrils' scaffolds are capable of supporting cells, promoting their survival and guiding their differentiation in neural lineage to repair the lesion. Despite its biocompatible nature, PLA is an electrically insulating material and thus it could be detrimental for increasingly common scaffolds' electric functionalization, aimed at accelerating the cellular processes. In this context, the European RISEUP project aims to combine high intense microseconds pulses and DC stimulation with neurogenesis, supported by a PLA microfibrils' scaffold. Methods: In this paper a numerical study on the effect of microfibrils' scaffolds on the E-field distribution, in planar interdigitated electrodes, is presented. Realistic microfibrils' 3D CAD models have been built to carry out a numerical dosimetry study, through Comsol Multiphysics software. Results: Under a voltage of 10 V, microfibrils redistribute the E-field values focalizing the field streamlines in the spaces between the fibers, allowing the field to pass and reach maximum values up to 100 kV/m and values comparable with the bare electrodes' device (without fibers). Discussion: Globally the median E-field inside the scaffolded electrodes is the 90% of the nominal field, allowing an adequate cells' exposure.

Changes in hydration of liposome membranes exposed to nanosecond electric pulses detected by wide-field Coherent anti-Stokes Raman microspectroscopy.

Electropulsation has become a powerful technological platform for electromanipulation of cells and tissues for various medical and biotechnological applications, but the molecular changes that underlay the very first initiation step of this process have not been experimentally observed. Here, we endowed a wide-field Coherent anti-Stokes Raman Scattering platform with an ad-hoc electromagnetic exposure device and we demonstrated, using artificial lipid vesicles (i.e. liposomes), that electropulsation is initiated by the increase of interstitial water content in liposome membranes. A pulse-dependent accumulation of the interstitial water molecules is observed in the membranes and a plausible mechanism supported by a computational electrochemical model is presented and discussed.

Electric-driven membrane poration: A rationale for water role in the kinetics of pore formation.

Electroporation is a well-established technique used to stimulate cells, enhancing membrane permeability by inducing reversible membrane pores. In the absence of experimental observation of the dynamics of pore creation, molecular dynamics studies provide the molecular-level evidence that the electric field promotes pore formation. Although single steps in the pore formation process are well assessed, a kinetic model representing the mathematical description of the electroporation process, is lacking. In the present work we studied the basis of the pore formation process, providing a rationale for the definition of a first-order kinetic scheme. Here, authors propose a three-state kinetic model for the process based on the assessed mechanism of water defects intruding at the water/lipid interface, when applying electric field intensities at the edge of the linear regime. The methodology proposed is based on the use of two robust biophysical quantities analyzed for the water molecules intruding at the water/lipid interface: (i) number of hydrogen bonds; (ii) number of contacts. The final model, sustained by a robust statistical sampling, provides kinetic constants for the transitions from the intact bilayer state to the hydrophobic pore state.

The Impact of Bilayer Rigidity on the Release from Magnetoliposomes Vesicles Controlled by PEMFs.

Stimuli-sensitive nanocarriers have recently been developed as a powerful tool in biomedical applications such as drug delivery, detection, and gene transfer techniques. Among the external triggers investigated, low intensity magnetic fields represent a non-invasive way to remotely control the release of compounds from a magneto-sensitive carrier. Magnetoliposomes (MLs), i.e., liposomes entrapping magnetic nanoparticles (MNPs), are studied due to their capacity to transport hydrophobic and hydrophilic agents, their easy production, and due to the ability of MNPs to respond to a magnetic actuation determining the triggered release of the encapsulated compounds. Here we investigated the design and optimization of the MLs to obtain an efficient on-demand release of the transported compounds, due to the magneto-mechanical actuation induced by applying low-intensity pulsed electromagnetic fields (PEMFs). In particular we studied the effect of the bilayer packing on the ability of MLs, with oleic acid-coated MNPs encapsulated in the bilayer, to respond to PEMFs application. Three kinds of MLs are produced with an increasing rigidity of the bilayer, defined as Liquid Disorder, Liquid Order, and Gel MLs and the delivery of a hydrophilic dye (as a model drug) is investigated. Results demonstrate the efficacy of the magnetic trigger on high-ordered bilayers, which are unable to dampen the perturbation produced by MNPs motion.

Galvanotactic Phenomenon Induced by Non-Contact Electrostatic Field: Investigation in a Scratch Assay.

Non-contact galvanotaxis as a way to drive the cells migration could be a promising tool for a variety of biomedical applications, such as wound healing control, avoiding the interaction between electrodes and cell cultures. To this regard, the efficacy of this electrical stimulus application has to be deeper studied to control physiological migratory phenomena in a remote way.Aim of this work is to provide an experimental investigation on the mobility of cells exposed to a static electric field in a "noncontact" mode, supported by a suitable modeling of the electric field distribution inside the experimental setup. In particular, scratch assays have been carried out placing the electrodes outside the cells medium support and changing the cells holder to study more than one configuration.Clinical Relevance- In this study the in vitro experiments on the non-contact galvanotaxis, together with the numerical simulations of the exposure setup, provide a way to investigate the effects that could affect an electrically drive cell migration.

Proof-of-Concept of Electrical Activation of Liposome Nanocarriers: From Dry to Wet Experiments.

The increasing interest toward biocompatible nanotechnologies in medicine, combined with electric fields stimulation, is leading to the development of electro-sensitive smart systems for drug delivery applications. To this regard, recently the use of pulsed electric fields to trigger release across phospholipid membranes of liposomes has been numerically studied, for a deeper understanding of the phenomena at the molecular scale. Aim of this work is to give an experimental validation of the feasibility to control the release from liposome vesicles, using nanosecond pulsed electric fields characterized by a 10 ns duration and intensity in the order of MV/m. The results are supported by multiphysics simulations which consider the coupling of three physics (electromagnetics, thermal and pore kinetics) in order to explain the occurring physical interactions at the microscopic level and provide useful information on the characteristics of the train of pulses needed to obtain quantitative results in terms of liposome electropermeabilization. Finally, a complete characterization of the exposure system is also provided to support the reliability and validity of the study.

Feasibility of Drug Delivery Mediated by Ultra-Short and Intense Pulsed Electric Fields.

The increasing interest towards biocompatible nanotechnologies in medicine, combined with electric fields stimulation, is leading to the development of electro-sensitive smart systems for drug delivery applications. Common examples of electro-sensitive materials include phospholipids that can be used to design nano-sized vesicles suitable for external electric actuation. To this regard, recently the use of pulsed electric fields to trigger release across phospholipid membranes has been numerically studied, for a deeper understanding of the phenomena at the molecular scale. Aim of this work is to give an experimental validation of the feasibility of controlling drug release from liposomes mediated by nanosecond pulsed electric fields.