Biology subjects

Genta, M.

Publications and source records attributed to Genta, M..

3 recordsLinked to original sources

bioRxiv2025

Astrocyte-Guided Maturation of Neural Constructs in a Modular Biosynthetic Hydrogel for Biohybrid Neurotechnologies

Bionic implants are increasingly used to restore neural function yet achieving a chronically stable neural interface remains challenging. Biohybrid neurotechnologies aim to overcome this limitation by integrating living tissue components that can promote long-term performance and functional integration with the nervous system. However, existing biomaterial coatings often lack the physiological complexity, cellular heterogeneity, and neurotrophic support required to sustain neural network formation. Here, we present a modular strategy which leverages astrocyte-guided mechanisms of neural network development. A biosynthetic hydrogel was developed using norbornene-functionalized poly(vinyl alcohol) and gelatin (PVA-GEL), crosslinked via visible light-triggered thiol-ene chemistry, to yield bioactive and highly tuneable scaffolds. A systematic characterization varying gelatin content and polymer weight enabled the identification an optimal formulation to promote astrocytic growth, while maintaining mechanical stability and degradation profiles that are compatible with brain implants. Co-encapsulation with neural progenitors promoted neuronal differentiation, neurite outgrowth, and the formation of synaptically competent networks. The construct developed into functional interfaces when in contact with brain tissue ex vivo, highlighting its potential as a biohybrid electrode coating. This work lays the foundation for the development of biologically guided biohybrid interfaces, towards seamless integration with the nervous system.

bioengineering↗

bioRxiv2025

Temporal Interference Stimulation Enhances Neural Regeneration

Neural regeneration therapies aim to treat neurodegeneration by promoting the proliferation and maturation of exogenous or endogenous neural progenitor cells (NPCs). However, their efficacy has been limited. Deep brain stimulation (DBS) via implanted electrodes has been shown to promote neurogenesis. However, its invasiveness precludes deployment in research and widespread clinical use. Temporal interference (TI) has emerged as a strategy for non-invasive, high-precision DBS using multiple kHz-range electric fields, with a frequency difference within the range of neural activity. Here, we validate the potential of TI stimulation for neural regeneration augmentation. We demonstrate that TI stimulation with a theta-band frequency difference enhances the maturation of embryonic neural progenitor cells in vitro. We then demonstrate that theta-band TI stimulation targeting the hippocampus enhances endogenous hippocampal neurogenesis in an in vivo mouse model of Alzheimers disease. By uncovering frequency-specific control of stem cell fate, we propose a clinically relevant regeneration strategy which avoids pharmacological or genetic manipulation. Our results demonstrate focal, non-invasive augmentation of deep-brain neural regeneration. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/670811v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@984165org.highwire.dtl.DTLVardef@1ed8bbdorg.highwire.dtl.DTLVardef@715057org.highwire.dtl.DTLVardef@151882f_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Endolysin B: A new archetype in M. tuberculosis treatment

So far it is thanks to antibiotics that illnesses, such as Tuberculosis (TB), are treatable. However, antimicrobial misuse combined with Mycobacterium tuberculosis phenotypic plasticity are nullifying the effects of the existing therapies. As a result, increasingly people are dying (one person dies of TB every 20 seconds), especially due to the rise of multi-and extensively drug-resistant strains. There is indeed a urgent need for new and more effective therapies, which should match the requirement of avoiding the rise in drug resistance. Among them, the use of bacteriophage - bacteria-restricted viruses - or simply phage lytic enzyme (i.e., endolysin) represents one of the most promising alternatives. All phages encode for the endolysin A (LysA), which degrades the bacteria cell wall, finally leading to the release of the newly synthesized virions. Nevertheless, mycobacteriophages (bacterial viruses selectively infecting mycobacteria), evolved the additional endolysin B (LysB) to selectively damage the complex mycobacteria cell wall, and to evade from their host. LysB, owing a lipolytic enzyme, can degrade the thick mycolic acid layer, and hence disrupt the integrity of the mycobacterial membrane. Despite its key role in mediating mycobacteria lysis, the molecular mechanism regulating LysB binding to its target remains poorly characterized. Herein, we selected Ms6LysB and created a fluorescent engineered version as a proxy to analyze LysB binding qualitatively and quantitatively to both the fast-growing non-pathogenic Mycobacterium smegmatis and the slow-growing pathogenic M. tuberculosis. Additionally, we shed light on LysB antimicrobial activity upon M. tuberculosis infection, by using alveolar-like mouse macrophages (mAMs) as a cellular model that closely recapitulates the natural niche of M. tuberculosis infection. Our study provides the proof-of-principle that Ms6 LysB binding to the outer mycobacterial membrane can impair M. tuberculosis growth homeostasis and that LysB retain its lytic properties even when internalized by mAMs. This lays the groundwork for the use of LysB as a new therapeutic strategy to undermine M. tuberculosis infection.

microbiology↗