The interplay between chemical conjugation and biologic performance in the development of alginate-based 3D matrices to mimic neural microenvironments

Carbohydrate Polymers, Journal Year: 2023, Volume and Issue: 323, P. 121412 - 121412

Published: Sept. 21, 2023

Biofunctionalization of polysaccharides is a widely used strategy for obtaining extracellular matrix (ECM)-mimicking biomaterials. Still, commonly employed chemistries present low reaction yields and the selection most adequate bioconjugation route can be challenging. Herein, we compared performance carbodiimide reductive amination synthesis tailored peptide-alginate hybrid hydrogels as neural tissue mimics. Reductive dramatically improved peptide grafting efficiency, with 50 % vs. 20 %, allowing 1.5 to 3-fold higher incorporation cell-adhesive matrix-metalloproteinases (MMP)-sensitive peptides, respectively. The conjugation dual-end reactive MMP-sensitive peptides promoted partial crosslinking, adjusting gelation, stiffness, degradability hydrogels. Such parameters depended on glycosidic position where bioactive binds, determined by adopted chemical strategy, this significantly impacted biological response. provided softer (50-210 Pa) fully degradable (60-100 weight loss) hydrogels, depending amount in formulation, contrasting stiffer (400 less (40 carbodiimide-based Due their opened polymer chain increased availability cells, such better supported 3D culture primary astrocytes, which high complexity process branching, development brain ECM-mimicking systems.

Language: Английский

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Tissue Compliance and Intracranial Pressure Responses to Large Intracerebral Hemorrhage in Young and Aged Spontaneously Hypertensive Rats

Hypertension, Journal Year: 2023, Volume and Issue: 81(1), P. 151 - 161

Published: Nov. 1, 2023

After a large intracerebral hemorrhage (ICH), the hematoma and swelling cause intracranial pressure (ICP) to increase, sometimes causing brain herniation death. This is partly countered by widespread tissue compliance, an acute decrease in volume distal stroke, at least young healthy animals. Intracranial compensation dynamics seem vary with age, but there no data on old animals or those hypertension, major factors influencing ICH risk outcome.We assessed volume, edema, ICP, functional deficits aged spontaneously hypertensive rats (SHRs) normotensive control strains after collagenase-induced ICH. Macroscopic microscopic fractions, such as contralateral hemisphere cortical thickness, neuronal morphology, were via histological stereological techniques.Hematoma was 52% larger versus SHRs; surprisingly, SHRs still experienced proportionally worse outcomes following ICH, 2× greater elevations edema ICP relative bleed 3× degree of compliance. Aged also equivalent neurological compared their younger counterparts, despite lack significant age-related behavioral effects. Importantly, compliance occurred across age groups not impaired hypertension age.Aged show considerable capacity for rely mechanisms more heavily settings elevated ICP. Therefore, response mass effect varies lifespan according chronic hypertension.

Language: Английский

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It takes two to remyelinate: A bioengineered platform to study astrocyte-oligodendrocyte crosstalk and potential therapeutic targets in remyelination

Biomaterials Advances, Journal Year: 2023, Volume and Issue: 151, P. 213429 - 213429

Published: April 25, 2023

The loss of the myelin sheath insulating axons is hallmark demyelinating diseases. These pathologies often lead to irreversible neurological impairment and patient disability. No effective therapies are currently available promote remyelination. Several elements contribute inadequacy remyelination, thus understanding intricacies cellular signaling microenvironment remyelination niche might help us devise better strategies enhance Here, using a new in vitro rapid myelinating artificial axon system based on engineered microfibres, we investigated how reactive astrocytes influence oligodendrocyte (OL) differentiation myelination ability. This culture enables uncoupling molecular cues from biophysical properties axons, allowing detailed study astrocyte-OL crosstalk. Oligodendrocyte precursor cells (OPCs) were cultured poly(trimethylene carbonate-co-ε-caprolactone) copolymer electrospun microfibres that served as surrogate axons. platform was then combined with previously established tissue glial scar model embedded 1 % (w/v) alginate matrices, which astrocyte phenotype acquired meningeal fibroblast conditioned medium. OPCs shown adhere uncoated differentiate into OL. Reactive found significantly impair OL ability, after six eight days co-culture system. Differentiation seen be correlated astrocytic miRNA release through exosomes. We reduction expression pro-myelinating miRNAs (miR-219 miR-338) an increase anti-myelinating (miR-125a-3p) content between quiescent astrocytes. Additionally, show OPC inhibition could reverted by rescuing activated ibuprofen, chemical inhibitor small rhoGTPase RhoA. Overall, these findings modulating function interesting therapeutic avenue for use will enable screening potential agents while providing valuable insight myelination/remyelination processes.

Language: Английский

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Exploring Piezo1, Piezo2, and TMEM150C in human brain tissues and their correlation with brain biomechanical characteristics

Molecular Brain, Journal Year: 2023, Volume and Issue: 16(1)

Published: Dec. 20, 2023

Abstract Unraveling the intricate relationship between mechanical factors and brain activity is a pivotal endeavor, yet underlying mechanistic model of signaling pathways in mechanotransduction remains enigmatic. To bridge this gap, we introduced an situ multi-scale platform, through which delineate comprehensive biomechanical traits white matter (WM), grey-white junctions (GW junction), pons across human tissue from four distinct donors. We investigate three-dimensional expression patterns Piezo1, Piezo2, TMEM150C, while also examining their associated histological features networks, particularly focusing on YAP/β-catenin axis. Our results showed that characteristics (including stiffness, spring term, equilibrium stress) with Piezo1 vary depending specific region. Moving beyond our result demonstrated significant positive correlations Piezo2 stiffness WM. Meanwhile, TMEM150C was shown to be correlated viscoelastic properties Given heterogeneity tissue, investigated TMEM150C. suggested three mechanosensitive proteins remained consistent different vertical planes within sections. findings not only establish as mechanosensors regulate region-specific activities but unveil paradigm connecting variations individuals.

Language: Английский

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Cellular signaling pathways in the nervous system activated by various mechanical and electromagnetic stimuli

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Oct. 4, 2024

Mechanical stimuli, such as stretch, shear stress, or compression, activate a range of biomolecular responses through cellular mechanotransduction. In the nervous system, studies on mechanical stress have highlighted key pathophysiological mechanisms underlying traumatic injury and neurodegenerative diseases. However, pathways triggered by stimuli in system has not been fully explored, especially compared to other body systems. This gap knowledge may be due wide variety methods definitions used research. Additionally, stimulation techniques ultrasound electromagnetic are increasingly utilized psychological neurorehabilitation treatments, it is vital understand biological order develop accurate models enhance therapeutic interventions. review aims summarize signaling activated various with particular focus mammalian system. Furthermore, we briefly discuss potential mechanosensors involved these processes.

Language: Английский

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A Preliminary Experimental Study on Biodegradation of 3D-Printed Samples from Biomass–Fungi Composite Materials

Journal of Composites Science, Journal Year: 2024, Volume and Issue: 8(10), P. 412 - 412

Published: Oct. 8, 2024

Products made from petroleum-derived plastic materials are linked to many environmental problems, such as greenhouse gas emissions and pollution. It is desirable manufacture products environmentally friendly instead of petroleum-based materials. biomass–fungi composite biodegradable can be utilized for packaging, construction, furniture. In materials, biomass particles (derived agricultural wastes) serve the substrate, fungal hyphae network binds together. There reported studies on 3D printing However, there no biodegradation 3D-printed samples this study, two types were used prepare printable mixture hemp hurd beechwood sawdust. The fungi strain was Trametes versicolor. Extrusion based print samples. left five days allow grow. then dried in an oven 4 h at 120 °C kill all buried soil using a mesh bag kept chamber 25 with relative humidity 48%. weight these measured every week over period three months. During testing period, test lost about 33% their original weight, whereas sawdust 30% weight. SEM (scanning electron microscope) micrographs showed presence zygospores samples, providing evidence soils. Additionally, difference peak intensity between control (for both sawdust) additional

Language: Английский

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Contact Inhibition and Mechanotransduction

Published: Dec. 19, 2023

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing formation cancerous tissues. CI can be further categorized into two distinct yet interrelated components: locomotion (CIL) and proliferation (CIP). These components have historically been viewed as separate processes, but emerging research indicates that they share both distinctive common pathways. Moreover, exhibit intriguing intersections with mechanotransduction, process involves cells sensing responding to mechanical forces. This review article describes intricate interplay between forces CI, shedding light on how these regulate CIL CIP. Emphasis is placed filamin A (FLNA)-mediated elucidating FLNA senses translates them biochemical signals cell proliferation. In addition FLNA, trans-acting factors (TAFs) emerge sensitive players in mechanotransduction process. presents methods identifying TAFs profiling associated changes chromatin structure, offering valuable insights regulation. Finally, it addresses unanswered questions fields delineates their possible future directions.

Language: Английский

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Exploring Piezo1, Piezo2, and TMEM150C in Human Brain Tissues and Their Correlation with Brain Biomechanical Characteristics

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 9, 2023

Abstract Unraveling the intricate relationship between mechanical factors and brain activity is a pivotal endeavor, yet underlying mechanistic model of signaling pathways in mechanotransduction remains enigmatic. To bridge this gap, we introduced an situ multi-scale platform, through which delineate comprehensive biomechanical traits white matter (WM), gray-white junctions (GW junction), pons across human tissue from four distinct donors. We investigate three-dimensional expression patterns Piezo1, Piezo2, TMEM150C, while also examining their associated histological features networks, particularly focusing on YAP/β-catenin axis. Our results showed that characteristics (including stiffness, spring term, equilibrium stress) with Piezo1 vary depending specific region. Moving beyond our result demonstrated significant positive correlations Piezo2 stiffness WM. Meanwhile, TMEM150C was shown to be correlated viscoelastic properties Given heterogeneity nature tissue, investigated TMEM150C. suggested three mechanosensitive proteins remained consistent different vertical planes within sections. findings not only establish as mechanosensors regulate region-specific activities, but unveil paradigm connecting activities variations individuals.

Language: Английский

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