Roberto Portillo-Lara

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 in vitro and in vivo. Still, 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 to target the deep brain. Here, we validate the potential of TI stimulation for neural regeneration augmentation in the central nervous system (CNS). First, we showed that TI stimulation modulated at the theta‐band frequency 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 Alzheimer's disease‐like amyloidosis. By uncovering frequency‐specific control of stem cell fate, we propose a clinically relevant regeneration strategy that avoids pharmacological or genetic manipulation. Our results enable focal, non‐invasive augmentation of deep‐brain neural regeneration via electrical stimulation.

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 or other biological components that can promote long‐term performance and functional integration with the nervous system. However, existing living biomaterial coatings often lack the physiological complexity, cellular heterogeneity, and neurotrophic support required to sustain neural network formation. Here, a modular strategy is presented which leverages astrocyte‐guided mechanisms of neural network development. A biosynthetic hydrogel is developed using norbornene‐functionalized poly(vinyl alcohol) and gelatin (PVA‐GEL), crosslinked via visible light‐triggered thiol‐ene chemistry, to yield bioactive and highly tunable scaffolds. A systematic characterization varying gelatin content and polymer weight enables 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 promotes neuronal differentiation, neurite outgrowth, and the formation of synaptically competent networks. The construct develops 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, toward seamless integration with the nervous system.

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.

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 Alzheimer’s 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

The study describes the development of a multi-layered electrode coating that was electrochemically characterised. A numerical model of the electric field was developed, and astrocytes were encapsulated within the biosynthetic layer.

Biohybrid design enables the engineering of neural interfaces with enhanced functionality and performance.

Brain–computer interfaces (BCIs) provide bidirectional communication between the brain and output devices that translate user intent into function. Among the different brain imaging techniques used to operate BCIs, electroencephalography (EEG) constitutes the preferred method of choice, owing to its relative low cost, ease of use, high temporal resolution, and noninvasiveness. In recent years, significant progress in wearable technologies and computational intelligence has greatly enhanced the performance and capabilities of EEG-based BCIs (eBCIs) and propelled their migration out of the laboratory and into real-world environments. This rapid translation constitutes a paradigm shift in human–machine interaction that will deeply transform different industries in the near future, including healthcare and wellbeing, entertainment, security, education, and marketing. In this contribution, the state-of-the-art in wearable biosensing is reviewed, focusing on the development of novel electrode interfaces for long term and noninvasive EEG monitoring. Commercially available EEG platforms are surveyed, and a comparative analysis is presented based on the benefits and limitations they provide for eBCI development. Emerging applications in neuroscientific research and future trends related to the widespread implementation of eBCIs for medical and nonmedical uses are discussed. Finally, a commentary on the ethical, social, and legal concerns associated with this increasingly ubiquitous technology is provided, as well as general recommendations to address key issues related to mainstream consumer adoption.

Orthopedic surgical procedures based on the use of conventional biological graft tissues are often associated with serious post‐operative complications such as immune rejection, bacterial infection, and poor osseointegration. Bioresorbable bone graft substitutes have emerged as attractive alternatives to conventional strategies because they can mimic the composition and mechanical properties of the native bone. Among these, bioactive glasses (BGs) hold great potential to be used as biomaterials for bone tissue engineering owing to their biomimetic composition and high biocompatibility and osteoinductivity. Here, we report the development of a novel composite biomaterial for bone tissue engineering based on the incorporation of a modified strontium‐ and lithium‐doped 58S BG (i.e., BG‐5/5) into gelatin methacryloyl (GelMA) hydrogels. We characterized the physicochemical properties of the BG formulation via different analytical techniques. Composite hydrogels were then prepared by directly adding BG‐5/5 to the GelMA hydrogel precursor, followed by photocrosslinking of the polymeric network via visible light. We characterized the physical, mechanical, and adhesive properties of GelMA/BG‐5/5 composites, as well as their in vitro cytocompatibility and osteoinductivity. In addition, we evaluated the antimicrobial properties of these composites in vitro, using a strain of methicillin‐resistant Staphylococcus Aureus. GelMA/BG‐5/5 composites combined the functional characteristics of the inorganic BG component, with the biocompatibility, biodegradability, and biomimetic composition of the hydrogel network. This novel biomaterial could be used for developing osteoinductive scaffolds or implant surface coatings with intrinsic antimicrobial properties and higher therapeutic efficacy.