In vitro and in vivo evaluation of a dextran-graft-polybutylmethacrylate copolymer coated on CoCr metallic stent

International audienceIntroduction: The major complications of stent implantation are restenosis and late stent thrombosis. PBMA polymers are used for stent coating because of their mechanical properties. We previously synthesized and characterized Dextrangraft-polybutylmethacrylate copolymer (Dex-PBMA) as a potential stent coating. In this study, we evaluated the haemocompatibility and biocompatibility properties of Dex-PBMA in vitro and in vivo.Methods: Here, we investigated: (1) the effectiveness of polymer coating under physiological conditions and its ability to release Tacrolimus®, (2) the capacity of Dex-PBMA to inhibit Staphylococcus aureus adhesion, (3) the thrombin generation and the human platelet adhesion in static and dynamic conditions, (4) thebiocompatibility properties in vitro on human endothelial colony forming cells (ECFC) and on mesenchymal stem cells (MSC) and in vivo in rat models, and (5) we implanted Dex-PBMA and Dex-PBMA TAC coated stents in neointimal hyperplasia restenosis rabbit model. Results: Dex-PBMA coating efficiently prevented bacterial adhesion and release Tacrolimus®. Dex-PBMA exhibit haemocompatibility properties under flow and ECFC and MSC compatibility. In vivo, no pathological foreign body reaction was observed neither after intramuscular nor intravascular aortic implantation. After Dex-PBMA and Dex-PBMATAC coated stents 30 days implantation in a restenosis rabbit model, an endothelial cell coverage was observed and the lumenpatency was preserved.Conclusion: Based on our findings, Dex-PBMA exhibited vascular compatibility and can potentially be used as a coating for metallic coronary stents

Extruded starch as novel shape-memory bioresorbable biomedical device

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RGTA based matrix therapy – A new branch of regenerative medicine in locomotion

Matrix therapy is an innovative, minimally invasive approach in the field of regenerative medicine, that aims to promote tissue regeneration by reconstructing the cellular microenvironment following tissue injury. This approach has significant therapeutic potential in the treatment of pathologies characterized by tissue inflammation and damage, or following injury, conditions which can be incapacitating and cost-consuming. Heparan sulfate mimics, termed ReGeneraTing Agents (RGTA®s) have emerged as a unifying approach to treat these diverse pathologies. Today, skin and corneal healing topical products have already been used in clinics, demonstrating a proof of concept in humans. In this review, we present key evidence that RGTA®s regenerate damaged tissue in bone, muscle, tendon and nerve, with astonishing results. In animal models of bone surgical defects and inflammatory bone loss, RGTA® induced healing of injured bones by controlling inflammation and bone resorption, and stimulated bone formation by coordinating vascularization, recruitment and differentiation of competent cells from specific niches, restoring tissue quality to that of uninjured tissue, evoking true regeneration. In models of muscle injury, RGTA® had marked effects on healing speed and quality, evidenced by increased muscle fiber density, maturation, vascularization and reduced fibrosis, more mature motor endplates and functional recovery. Applications merging RGTA®-based matrix therapy and cell therapy, combining Extra-Cellular Matrix reconstruction with cells required for optimal tissue repair show significant promise. Hence restoration of the proper microenvironment is a new paradigm in regenerative medicine. Harnessing the potential of RGTA® in this brave, new vision of regenerative therapy will therefore be the focus of future studies

Organ Repair, Hemostasis, and In Vivo Bonding of Medical Devices by Aqueous Solutions of Nanoparticles

International audienceSutures are traumatic to soft connective tissues, such as liver or lungs. Polymer tissue adhesives require complex in vivo control of polymerization or cross-linking reactions and currently suffer from being toxic, weak, or inefficient within the wet conditions of the body. Herein, we demonstrate using Stober silica or iron oxide nanoparticles that nanobridging, that is, adhesion by aqueous nanoparticle solutions, can be used in vivo in rats to achieve rapid and strong closure and healing of deep wounds in skin and liver. Nanoparticles were also used to fix polymer membranes to tissues even in the presence of blood flow, such as occurring after liver resection, yielding permanent hemostasis within a minute. Furthermore, medical devices and tissue engineering constructs were fixed to organs such as a beating heart. The simplicity, rapidity, and robustness of nanobridging bode well for clinical applications, surgery, and regenerative medicine

Impact de la localisation de la masse grasse sur l’oxydation des substrats énergétiques à l’exercice chez la femme normo-pondérée

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Evaluation of dense collagen matrices as medicated wound dressing for the treatment of cutaneous chronic wounds

International audienceCutaneous chronic wounds are characterized by an impaired wound healing which may lead to infection and amputation. When current treatments are not effective enough, the application of wound dressings is required. To date, no ideal biomaterial is available. In this study, highly dense collagen matrices have been evaluated as novel medicated wound dressings for the treatment of chronic wounds. For this purpose, the structure, mechanical properties, swelling ability and in vivo stability of matrices concentrated from 5 to 40 mg mL(-1) were tested. The matrix stiffness increased with the collagen concentration and was associated with the fibril density and thickness. Increased collagen concentration also enhanced the material resistance against accelerated digestion by collagenase. After subcutaneous implantation in rats, dense collagen matrices exhibited high stability without any degradation after 15 days. The absence of macrophages and neutrophils evidenced their biocompatibility. Subsequently, dense matrices at 40 mg mL(-1) were evaluated as drug delivery system for ampicillin release. More concentrated matrices exhibited the best swelling abilities and could absorb 20 times their dry weight in water, allowing for an efficient antibiotic loading from their dried form. They released efficient doses of antibiotics that inhibited the bacterial growth of Staphylococcus Aureus over 3 days. In parallel, they show no cytotoxicity towards human fibroblasts. These results show that dense collagen matrices are promising materials to develop medicated wound dressings for the treatment of chronic wounds

Fat mass localization alters fuel oxidation during exercise in normal weight women

International audiencePurpose: Abdominal and lower body fat mass tissues exhibit particular metabolic profiles at rest and during exercise. However, data are missing in normal weight women during exercise. The purpose of this study was to investigate the effect of low (LA/LB) and high (HA/LB) abdominal to lower body (A/LB) fat mass ratio on metabolic and hormonal responses during exercise in premenopausal normal weight women. Methods: After preliminary testing ((V) over dotO(2max) and body composition assessment), substrate oxidation (RER, lipid, and carbohydrate oxidation rates), metabolic response (glycerol, free fatty acids, and glucose), and hormonal response (insulin, growth hormone, atrial natriuretic peptide, adrenaline, and noradrenaline) were determined during exercise (45 min at 65% of (V) over dotO(2max)) in 21 premenopausal normal weight women (10 HA/LB women vs 11 LA/LB women). Results: Waist circumference was significantly higher in HA/LB women compared with LA/LB women (P < 0.01). No difference in other anthropometric characteristics, (V) over dotO(2max), and resting blood values was observed between the two groups. LA/LB subjects exhibited greater lipid oxidation rates compared with HA/LB women during exercise (P < 0.01). This occurred with lower plasma insulin (P < 0.05) and glucose (P < 0.05) concentrations and higher plasma free fatty acids (P < 0.05), glycerol (P < 0.05), growth hormone (P < 0.05), and atrial natriuretic peptide levels (P G 0.01) during exercise in the LA/LB group compared with the HA/LB group. Conclusions: The present study demonstrated that LA/LB women exhibited an increase in whole-body lipid mobilization and use during exercise compared with HA/LB counterparts. This greater reliance on lipid as fuel metabolism during exercise could be explained by substrate availability and metabolic and hormonal responses. It appeared that LA/LB women exhibited greater metabolic flexibility during an exercise bout of 45 min at 65% of (V) over dotO(2max) on cycle ergometer

Design, fabrication, and implantation of tube-shaped devices for the treatment of salivary duct diseases

International audienceIntroduction: Starch-based materials were designed using a special extrusion die in order to obtain a tube-shaped device for application to salivary duct treatment in the field of endoscopy, i.e., sialendoscopy. Methods: Extrusion process was used to produce starch tubes. Mechanical properties of the dry tube before implantation were determined using an axial compression test. A finite element study was carried out to simulate the behavior of the hydrated tube under external axial pressure. Hydrolysis of these devices in a simulated salivary solution was studied, as well as its glycerol kinetics release. An animal short-term implantation model for salivary ducts was proposed as a feasibility study for starch tube-shaped devices. Results: A continuous production of regular and size-controlled tubes was obtained. The very small diameter obtained, less than 2 mm, corresponds to the requirement of being insertable in a human salivary duct using sialendoscopy guidewire. Finite element analysis showed that the starch tube can still support an external pressure higher than 0.2 MPa without irreversible damage. After 4 days of implantation, the host response is encouraging and the inflammatory response for this type of procedure remains normal. Conclusion: These devices were adapted to sialendoscopic guidewires and able to be implanted in the salivary ducts of pigs. If a longer lasting tube is required, the crystallinity of the starch material should be improved