Biology subjects

Sosnik, A.

Publications and source records attributed to Sosnik, A..

4 recordsLinked to original sources

bioRxiv2026

Self-Terminating Bilayer Hydrogel Actuators via Enzyme-Programmed Mechanical Feedback

Autonomous soft materials that can actuate, perform a function, and then self-terminate without external intervention remain difficult to realize. Here, a bilayer hydrogel actuator fabricated by digital light processing-based 3D bioprinter is introduced that couples rapid thermoresponsive deformation with slower enzyme-programmed mechanical feedback to achieve self-regulated shape transformation and autonomous recovery. The system integrates a poly(N-isopropylacrylamide) actuation layer with a bovine serum albumin-poly(ethylene glycol) diacrylate enzyme-programmed layer loaded with trypsin. Above the lower critical solution temperature, deswelling of the actuation layer generates a strain mismatch across the bilayer and drives rapid closure. In parallel, proteolytic cleavage of albumin domains progressively softens the enzyme-programmed layer, reduces interlayer constraint, and acts as an intrinsic mechanical off-switch that relaxes curvature and restores the open state. This materials logic enables sustained enzyme release, time-dependent modulus loss, and autonomous shape recovery without staged external triggers. As a proof-of-concept, this platform is implemented as a gastrointestinal-retentive hydrogel gripper for localized intestinal enzyme delivery, where it exhibits thermally triggered gripping, millinewton-scale gripping force, autonomous reopening, and robust ex vivo retention on porcine small intestine under dynamic motion. These findings establish enzyme-programmed mechanical feedback as a general design strategy for self-regulated soft actuators and therapeutic materials with built-in functional lifetimes.

bioengineering↗

bioRxiv2025

Nose-to-Brain Administration of Cannabidiol-Loaded Polymeric Micelles Improves the Core Behavioral Symptoms of Autism Spectrum Disorder

Neurodevelopmental disorders including autism spectrum disorder (ASD) affect 5.9% of the global population. Research shows the potential therapeutic use of cannabidiol (CBD) to treat different neurodevelopmental disorders, including ASD. Intranasal drug delivery (i.n.) is a non-invasive and painless administration route that enhances drug bioavailability in the brain by bypassing the blood-brain barrier. However, i.n. has limited bioavailability due to the low nasal mucosa permeability. Various polymeric nanoparticles have been investigated for i.n. delivery with different successes. In this study, we developed and characterized polymeric micelles of the poly(ethylene oxide)-b-poly(propylene oxide) block copolymer Pluronic(R) F127 loaded with 25% w/w CBD for nose-to-brain delivery in ASD. CBD-loaded polymeric micelles display a hydrodynamic diameter of 41 {+/-} 1 nm by Intensity and 23 {+/-} 1 nm by Number, as measured by dynamic light scattering, and showed very good compatibility and permeability in the human nasal septum cell line RPMI 2650, an in vitro model of the nasal epithelium. The accumulation of CBD-loaded polymeric micelles upon i.n. administration to autistic rats is confirmed by bioimaging. The pharmacokinetics of CBD upon i.n. (dose of 5 mg/kg) and oral (15 mg/kg) administration of the loaded polymeric micelles shows a 27.8% increase of the CBD concentration in the brain 20 min of autistic rats after i.n. administration, despite the 3-fold decrease in the dose. Finally, the efficacy of this nanoformulation to improve the core symptoms of ASD is demonstrated in behavioral studies in a rat model of the disorder.

neuroscience↗

bioRxiv2022

Drug-eluting biodegradable metals and metal-ceramic composites: High strength and delayed drug release

Biodegradable metals emerged as promising temporary bone implants. The integration of additional features such as local drug delivery (LDD) can also support their osteointegration, promote bone regeneration, and prevent biomaterial-centered infections that are difficult to treat. LDD is achieved by drug-eluting coatings or porous implants where the drug is impregnated after implant fabrication because the high temperatures used during conventional production processes would result in their thermal decomposition. We produced biodegradable iron (Fe)-based vancomycin (VH)-eluting metals and metal-ceramic composites by a simple high-pressure consolidation/cold sintering (CS) process at room temperature that display high mechanical strength and antibacterial activity. Aiming to expand the application of this production method and shed light into the drug loading and release mechanisms in this type of biomaterials, this work reports on the production and characterization of VH-loaded Fe and Fe-iron oxide (Fe2O3) composites (Fe-Fe2O3). We use focus ion beam milling for the first time to investigate the drug-metal interface and investigate the mechanical and degradation properties of VH-free and VH-loaded Fe and Fe-Fe2O3. Results show very high mechanical strength of drug-eluting Fe and Fe-Fe2O3 composites (up to than 780 MPa under compression, exceeding the maximum strength of cancellous bone more than three times) accompanied by a delayed drug release. Then, we confirm the good antimicrobial activity against Staphylococcus aureus and cell compatibility with the murine embryonic fibroblast cell line NIH/3T3 in vitro. Overall results confirm the promise of drug-eluting metals and metal-ceramic composites for LDD in bone.

bioengineering↗

bioRxiv2020

Multicellular Organoids of the Neurovascular Blood-Brain Barrier: A New Platform for Precision Neuronanomedicine

The treatment of neurological disorders (NDs) is challenged by low drug permeability from the systemic circulation into the central nervous system (CNS) owing to the presence of the blood-brain barrier (BBB). Neuronanomedicine investigates nanotechnology strategies to target the brain and improve the therapeutic outcome in NDs. Two-dimensional adherent cell BBB models show substantial phenogenomic heterogeneity and their ability to predict the permeability of molecules and nanoparticles into the brain is extremely limited. Thus, the high-throughput screening of CNS nanomedicines relies on the use of animal models. To address this dearth, 3D organoids that mimic the in vivo physiology are under development. Still, there exist concerns about the standardization and scale-up of the production process, their proper characterisation, and their industrial application. In this work, we report on a novel multicellular organoid of the neurovascular blood-brain barrier (NV-BBB) that recapitulates the regulated syncytium of human endothelial cells and the function of the human BBB. For this, an advanced organoid comprising human brain microvascular endothelial cells, brain vascular pericytes and human astrocytes combined with primary neurons and microglia isolated from neonate rats is bio-fabricated without the use of an extracellular matrix. The structure and function are fully characterized by confocal laser scanning fluorescence microscopy, light sheet fluorescence microscopy, scanning transmission electron microscopy, cryogenic-scanning electron microscopy, western blotting, RNA-sequencing and quantitative gene expression by quantitative polymerase chain reaction analysis. This bulk of these self-assembloids is comprised of neural cells and microglia and the surface covered by endothelial cells that act as a biological barrier that resembles the BBB endothelium. In addition, the formation of neuron-microglia morphofunctional communication sites is confirmed. Analysis of key transcriptomic expressions show the up-regulation of selected BBB-related genes including tight junction proteins, solute carriers, transporters of the ATP-binding cassette superfamily, metabolic enzymes, and prominent basement membrane signatures. Results confirmed the more efficient cell-cell communication in 3D organoids made of multiple neural-tissue cells than in 2D endothelial cell monocultures. These multicellular organoids are utilized to screen the permeability of different polymeric, metallic, and ceramic nanoparticles. Results reveal penetration through different mechanisms such as clathrin-mediated endocytosis and distribution patterns in the organoid that depend on the nanoparticle type, highlighting the promise of this simple, reproducible and scalable multicellular NV-BBB organoid platform to investigate the BBB permeability of different nanomaterials in nanomedicine, nanosafety, and nanotoxicology.

bioengineering↗