Recent Developments in Electroporation

Introduction

Following the success of the first Special Issue promoted by the 5^th World Congress on Electroporation, held in Rome in September 2024, we are pleased to present the second collection of peer-reviewed contributions dedicated to the most recent advances in electroporation science and technology. This Part II further consolidates but goes beyond the key themes that emerged from the Congress and from the first part of the Special Issue: Technological reliability of electrodes and devices, microdosimetry-driven pulse optimization, mechanistic insights into electrotransfer and intracellular modulation, predictive numerical modeling for clinical translation, and expanding applications beyond oncology into bioelectronic medicine and biotechnology are presented. Together, these articles reflect a field that is rapidly evolving from empirical protocol development toward quantitatively controlled, mechanism-guided, and clinically predictive bioelectric interventions.

Some Highlights

In this issue, a first group of studies addresses a critical yet sometimes underestimated dimension of electroporation-based therapies: electrode integrity and procedural reliability. There are two articles by Maglietti and colleagues. The first (“Electrode corrosion in electrochemotherapy can hinder treatment efficacy”) demonstrates how electrochemical degradation phenomena can alter local electric field distribution, modify tissue microenvironments, and, ultimately, compromise treatment reproducibility. The second (“Electrode tip wear increases needle deflection and procedural complexity in electrochemotherapy”) complimentarily shows that mechanical wear of needle tips increases deflection during insertion, raising procedural complexity, and potentially affecting targeting accuracy. These contributions remind us that electric pulse optimization alone is insufficient; material science, electrochemistry, and mechanical performance are integral components of therapeutic precision.

Microdosimetry emerges as a paradigm in several articles. In “Microdosimetry-driven optimization of µsPEF stimulation for stem cell neurogenesis in implantable bio-hybrid devices,” Dolciotti and colleagues present a quantitative framework aimed at tailoring microsecond pulsed electric fields for promoting stem-cell-derived neurogenesis within implantable bio-hybrid systems. Extending this approach, “Microdosimetric calibration of µsPEF ctimulation cross electrodes technologies for the RISEUP Project” by Liberti and colleagues provides cross-platform calibration strategies, enabling reproducibility and standardization across different electrode technologies. In parallel, “Optimizing electroporation pulses by balancing ablation and pH-induced damage: a trajectory-based framework” by Marshall and colleagues introduces a dynamic optimization strategy that integrates ablative effects with pH-mediated tissue damage, proposing trajectory-based electric pulse design to maximize therapeutic benefit while minimizing collateral injury. Collectively, these studies demonstrate a decisive shift toward microdosimetry-informed protocols in which spatial and temporal controls of delivered energy become interesting aspects.

Mechanistic and translational insights into electrotransfer and intracellular signaling are also prominently featured. “Dependence of efficiency of electrotransfer of plasmid DNA of different sizes on the pulse strength and pulse duration” by Šatkauskas and colleagues systematically analyses how plasmid size interacts with electric pulse amplitude and duration, offering practical guidance for gene therapy and DNA vaccination strategies.

Moving beyond membrane permeabilization as a purely transport phenomenon, “Calcium signaling hacking by MILD electroporation: a novel approach for bioelectronic medicine” by Ivorra and colleagues proposes the selective modulation of intracellular calcium signaling through minimally invasive electroporation protocols. Similarly innovative, “Modulation of contactless high intensity pulsed electromagnetic field induced electroporation and gene delivery efficacy using various nanoparticles” by Polajžer et al. explores the synergy between contactless high-intensity pulsed electromagnetic fields and nanoparticles, revealing that nanoscale agents can enhance and modulate electroporation-mediated gene delivery. These articles collectively expand the boundaries of the field toward hybrid electro-nanobiotechnological platforms.

The translational trajectory of electroporation is further strengthened by the article entitled “An updated numerical workflow for predicting clinical outcomes of irreversible electroporation in hepatocellular carcinoma” by Poignard and colleagues. This contribution presents an advanced computational pipeline integrating electric field simulations, tissue properties, and procedural parameters to predict clinical outcomes in liver tumors.

The scope of this issue extends beyond biomedical oncology. Thus, the article on “Application of pulsed electric fields in algal and bacterial cocultures: investigating bacterial responses and purity of agal protein extract” by Jonynaitė and colleagues investigates pulsed electric field applications in algal–bacterial cocultures, analyzing microbial responses and the purity of algal protein extracts. This work illustrates how electroporation technologies can contribute to sustainable bioprocessing and alternative protein production.

To finish, first, Ann Rajnicek presents her usual collection of recent key articles in the burgeoning field of bioelectricity in the “Buzz.” Finally, we are delighted to include the special article on “My Experiments in Bioelectricity” by Professor Lluis Mir, one of the pioneers of the electroporation field. His personal account of the various “eureka” moments he experienced in his long, distinguished career makes most insightful reading.

Concluding Remarks

As this second part of the Special Issue demonstrates, electroporation research is entering a new phase characterized by quantitative rigor, device-aware optimization, mechanistic refinement, and predictive clinical modeling. The contributions collected here not only reflect the scientific momentum generated by the 5^th World Congress on Electroporation but also chart a forward-looking agenda in which physics, engineering, biology, and medicine converge within an increasingly integrated bioelectric framework. We are confident that this body of work will stimulate further collaborations across disciplines and accelerate the translation of electroporation technologies into precise, reliable, and “next-generation” bioelectric devices and therapies.