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Coradin, T.

Publications and source records attributed to Coradin, T..

7 recordsLinked to original sources

A Murine Model of Mycobacterium abscessus Encapsulated in Alginate-Beads: Advancing Toward a Chronic Infection Model

BackgroundThe increasing incidence of Mycobacterium abscessus (M. abscessus) lung infections, together with its intrinsic multidrug resistance, highlights the need for new therapeutic regimens. However, the lack of a reliable chronic infection model in immunocompetent mice limits preclinical evaluation. MethodsTo mimic the bronchial environment of infected patients, we evaluated the effect of encapsulating M. abscessus in alginate beads on infection progression in BALB/cJRJ mice following intratracheal inoculation, compared with intranasal infection using non-encapsulated bacteria. The impact of dexamethasone treatment (DEX) was also assessed. Bacterial loads in lungs, spleen, liver, and kidneys were quantified over time in untreated and antibiotic-treated mice. Lung inflammation was evaluated by measuring IFN-{gamma} and TNF- levels. In vitro, the activity of imipenem and bedaquiline was assessed against free or alginate-encapsulated M. abscessus. ResultsCompared with intranasal infection, intratracheal infection with alginate-encapsulated bacteria resulted in slower pulmonary clearance and greater extrapulmonary dissemination. DEX further enhanced these features, reducing lung clearance, increasing dissemination, and amplifying lung inflammation. Bedaquiline showed no effect, whereas imipenem efficacy depended on treatment timing. For both drugs, alginate encapsulation reduced in vitro antibacterial activity. ConclusionThis model represents a step toward a chronic M. abscessus infection model characterized by moderate lungs clearance, extrapulmonary dissemination, and pronounced inflammatory responses. Reduced antibiotic activity against alginate-encapsulated bacteria may more accurately predict treatment efficacy in humans than activity measured against free bacteria.

microbiology↗

Does Infection Progression of Mycobacterium abscessus Depend on Sex, Age, and Mouse strain?

The lack of a reliable chronic murine model limits drugs evaluation against Mycobacterium abscessus. Models show discrepancies, especially regarding host factors (mouse strain, sex and age). Using beads-model, we compared BALB/cJRJ and C57BL/6NCrl across sexes and ages. BALB/cJRJ showed more sustained infection and lower variability, with no significant sex- or age-related differences. Considering these results and the higher prevalence of NTM pulmonary infections in female patients, 5-6 weeks-old female BALB/cJRJ are appropriate for M. abscessus beads-model.

microbiology↗

Evaluation of Silica and Bioglass Nanomaterials in Pulp-Like Living Materials

Although silicon is a widespread constituent in dental materials, its possible influence on teeth formation and repair remains largely unexplored. Here we have studied the effect of two silicic acid-releasing nanomaterials, silica and bioglass, on a living model of pulp consisting of dental pulp stem cells seeded in dense type I collagen hydrogels. Silica nanoparticles and released silicic acid had little effect on cell viability and mineralization efficiency but impacted metabolic activity, delayed matrix remodeling and led to heterogeneous cell distribution. Bioglass improved cell metabolic activity and led to a homogenous dispersion of cells and mineral deposits within the scaffold. These results suggest that the presence of calcium ions in bioglass is not only favorable to cell proliferation but can also counter-balance the negative effects of silica and silicic acid. Both chemical and biological processes should therefore be considered when investigating the effect of silicon-containing materials on dental tissues.

bioengineering↗

Multivalent Clustering of Adhesion Ligands in Nanofiber-Nanoparticle Composites

Because the positioning and clustering of biomolecules within the extracellular matrix dictates cell behaviors, the engineering of biomaterials incorporating bioactive epitopes with spatial organization tunable at the nanoscale is of primary importance. Here we used a highly modular composite approach combining peptide amphiphile (PA) nanofibers and silica nanoparticles, which are both easily functionalized with one or several bioactive signals. We show that the surface of silica nanoparticles allows the clustering of RGDS bioactive signals leading to improved adhesion and spreading of fibroblast cells on composite hydrogels at an epitope concentration much lower than in PA-only based matrices. Most importantly, by combining the two integrin-binding sequences RGDS and PHSRN on nanoparticle surfaces, we improved cell adhesion on the PA nanofiber/particle composite hydrogels, which is attributed to synergistic interactions known to be effective only for peptide intermolecular distance of ca. 5 nm. Such composites with soft and hard nanostructures offer a strategy for the design of advanced scaffolds to display multiple signals and control cell behavior.

bioengineering↗

Thrombin-free polymerization leads to pure fibrin(ogen) materials with extended processing capacity

Fibrin is a key protein for various clinical applications such as tissue reconstruction. However, in contrast to type I collagen, fibrin shaping has so far faced major limitations related to the necessity to add thrombin enzyme to fibrinogen precursors to induce fibrin self-assembly. Here we report a thrombin-free gelation pathway of fibrinogen solutions by incubation at 37{degrees}C in mild acidic conditions. We unravel the biochemical mechanisms underlying the gelation process and draw comparison between fibrinogen and fibrin at both molecular and supramolecular levels in these conditions. The protocol enables to control the viscosity of fibrin(ogen) solutions, and to induce fibrin(ogen) gel formation by simple 37{degrees}C incubation, with a reinforcement effect at neutralization. It facilitates processing of fibrin(ogen) materials, for coating, molding and extrusion, and offers new possibilities such as 3D printing. This approach is further compatible with type I collagen processing and can provide advanced tissue engineering scaffolds with high bioactivity.

bioengineering↗

Differential myoblast and tenoblast affinity to collagen, fibrin and mixed threads in the prospect of muscle-tendon junction modelisation

The myotendinous junction transfers forces from muscle to tendon. As such, it must hold two tissues of completely different biological and cellular compositions as well as mechanical properties (kPa-MPa to MPa-GPa) and is subject to frequent stresses of high amplitude. This region remains a weak point of the muscle-tendon unit and is involved in frequent injuries. We here produce fibrin (40 mg/mL, E0 =0.10 {+/-} 0.02 MPa) and collagen (60 mg/mL, E0=0.57 {+/-} 0.05 MPa) threads as well as mixed collagen:fibrin threads (3:2 in mass, E0 = 0.33 {+/-} 0.05 MPa) and investigate the difference of affinity between primary murine myoblasts and tenoblasts. We demonstrate a similar behavior of cells on mixed and fibrin threads with high adherence of tenoblasts and myoblasts, in comparison to collagen threads that promote high adherence and proliferation of tenoblasts but not of myoblasts. Besides, we show that myoblasts on threads differentiate but do not fuse, on the contrary to 2D control substrates, raising the question of the effect of substrate curvature on the ability of myoblasts to fuse in vitro.

bioengineering↗

Unveiling cells' local environment during cryopreservation by correlative in situ spatial and thermal analyses

Cryopreservation is the only fully established procedure to extend the lifespan of living cells and tissues, a key to activities spanning from fundamental biology to clinical practice. Despite its prevalence and impact, central aspects of cryopreservation, such as the cells physico-chemical environment during freezing, remain elusive. Here we address that question by coupling in situ microscopic directional freezing to visualize cells and their surroundings during freezing with the freezing medium phase diagram. We extract the freezing medium spatial distribution in cryopreservation, providing a tool to describe the cell vicinity at any point during freezing. We show that two major events define the cells local environment over time: the interaction with the moving ice front and with the vitreous moving front - a term we introduce here. Our correlative strategy may be applied to cells relevant in clinical research and practice, and help designing new cryoprotective media based on local physico-chemical cues.

biophysics↗