Graciela Pavon-Djavid

Development of a New Polypropylene-Based Suture: Plasma Grafting, Surface Treatment, Characterization, and Biocompatibility Studies

Polypropylene sutures (PP) are already used in surgery. Because microbial infection leads to complications, we developed antimicrobial PP suture by plasma-induced graft polymerization of acrylic acid followed by chitosan binding on the remaining carboxyl groups. Mechanical properties and surface morphologies were analyzed on these sutures. Tetracycline hydrochloride (TC) or nanosilver (NS) was then immobilized to PP. The resulting PP sutures evidenced drug release properties and antimicrobial activity in vitro. PP implanted in vivo for 30 days in the muscle of rats showed the absence of adverse effects and a tissue organization. This new polypropylene suture with suitable antimicrobial features appears to be a promising macromolecular material for clinical and cosmetic applications.

Astaxanthin from Haematococcus pluvialis Prevents Oxidative Stress on Human Endothelial Cells without Toxicity

Astaxanthin, a powerful antioxidant, is a good candidate for the prevention of intracellular oxidative stress. The aim of the study was to compare the antioxidant activity of astaxanthin present in two natural extracts from Haematococcus pluvialis, a microalgae strain, with that of synthetic astaxanthin. Natural extracts were obtained either by solvent or supercritical extraction methods. UV, HPLC-DAD and (HPLC-(atmospheric pressure chemical ionization (APCI)+)/ion trap-MS) characterizations of both natural extracts showed similar compositions of carotenoids, but different percentages in free astaxanthin and its ester derivatives. The Trolox equivalent antioxidant capacity (TEAC) assay showed that natural extracts containing esters displayed stronger antioxidant activities than free astaxanthin. Their antioxidant capacities to inhibit intracellular oxidative stress were then evaluated on HUVEC cells. The intracellular antioxidant activity in natural extracts was approximately 90-times higher than synthetic astaxanthin (5 µM). No modification, neither in the morphology nor in the viability, of vascular human cells was observed by in vitro biocompatibility study up to 10 µM astaxanthin concentrations. Therefore, these results revealed the therapeutic potential of the natural extracts in vascular human cell protection against oxidative stress without toxicity, which could be exploited in prevention and/or treatment of cardiovascular diseases.

Effect of crystallinity and plasticizer on mechanical properties and tissue integration of starch-based materials from two botanical origins

The application of starch-based materials for biomedical purposes has attracted significant interest due to their biocompatibility. The physical properties and crystal structure of materials based on potato starch (PS) and amylomaize starch (AMS) were studied under physiological conditions. PS plasticized with 20% glycerol presented the best mechanical properties with an elastic modulus of 1.6MPa and a weak swelling, remaining stable for 30 days. The in vitro cell viability of 3T3 cells after contact with extracts from PS and AMS with 20% glycerol is 72% and 80%, respectively. PS presented good tissue integration and no significant inflammation or foreign body response after 30 days intra-muscular implantation in a rat model, contrary to AMS. It was shown that glycerol plasticization favors a fast B-type crystallization of PS materials, enhancing their mechanical strength and durability, and making them a good candidate for bioresorbable and biocompatible materials for implantable medical devices.

Carotenoids from microalgae to block oxidative stress

Reactive oxygen species (ROS) are produced under normal physiological conditions and involved in several cellular biochemical processes. Their external or endogenous overproduction induces a disruption of redox signaling and control known as oxidative stress. Under oxidative stress, the cell membrane structures, enzyme functions and gene expression are compromised leading to the pathogenesis of several chronic inflammatory diseases including the cardiovascular pathologies. Attempts to find new therapeutic molecules capable of blocking the oxidative stress are of crucial importance. Owing to their anti-inflammatory and antioxidant properties, carotenoids have been proposed for the prevention and treatment of chronic diseases. In particular, microalgae carotenoids such as astaxanthin and lutein have shown promising results. Due to their protective action, these carotenoids could have a high potential to treat ROS-related pathologies. However, a better understanding of their biological mechanisms of action and the appropriate administration and uses of delivery systems are needed in the prevention and treatment of chronic pathologies.

Oxidative Stress Regulation on Endothelial Cells by Hydrophilic Astaxanthin Complex: Chemical, Biological, and Molecular Antioxidant Activity Evaluation

An imbalance in the reactive oxygen species (ROS) homeostasis is involved in the pathogenesis of oxidative stress-related diseases. Astaxanthin, a xanthophyll carotenoid with high antioxidant capacities, has been shown to prevent the first stages of oxidative stress. Here, we evaluate the antioxidant capacities of astaxanthin included within hydroxypropyl-beta-cyclodextrin (CD-A) to directly and indirectly reduce the induced ROS production. First, chemical methods were used to corroborate the preservation of astaxanthin antioxidant abilities after inclusion. Next, antioxidant scavenging properties of CD-A to inhibit the cellular and mitochondrial ROS by reducing the disturbance in the redox state of the cell and the infiltration of lipid peroxidation radicals were evaluated. Finally, the activation of endogenous antioxidant PTEN/AKT, Nrf2/HO-1, and NQOI gene and protein expression supported the protective effect of CD-A complex on human endothelial cells under stress conditions. Moreover, a nontoxic effect on HUVEC was registered after CD-A complex supplementation. The results reported here illustrate the need to continue exploring the interesting properties of this hydrophilic antioxidant complex to assist endogenous systems to counteract the ROS impact on the induction of cellular oxidative stress state.

Peristrut microhemorrhages : a possible cause of in-stent neoatherosclerosis?

BACKGROUND In-stent neoatherosclerosis is characterized by the delayed appearance of markers of atheroma in the subintima, but the pathophysiology underlying this new disease entity remains unclear. METHODS AND RESULTS We collected 20 human coronary artery stents by removal from explanted hearts. The mean duration of stent implantation was 34 months. In all samples, neoatherosclerosis was detected, particularly in peristrut areas. It consisted of foam cells and cholesterol clefts, with or without calcification, associated with neovascularization. Iron and glycophorin-A were present in peristrut areas, as well as autofluorescent ceroids. Moreover, in response to neoatherosclerosis, tertiary lymphoid organs (tissue lymphoid clusters) often developed in the adventitia. Some of these features could be reproduced in an experimental carotid stenting model in rabbits fed a high-cholesterol diet. Foam cells were present in all samples, and peristrut red blood cells (RBCs) were also detected, as shown by iron deposits and Bandeiraea simplicifiola isolectin-B4 staining of RBC membranes. Finally, in silico models were used to evaluate the compliance mismatch between the rigid struts and the distensible arterial wall using finite element analysis. They show that stenting approximately doubles the local von Mises stress in the intimal layer. CONCLUSIONS We show here that stent implantation both in human and in rabbit arteries is characterized by local peristrut microhemorrhages and finally by both cholesterol accumulation and oxidation, triggering together in-stent neoatherosclerosis. Our data indicate that these processes are likely initiated by an increased mechanical stress due to the compliance mismatch between the rigid stent and the soft wall.

Gelatin — Oxidized carboxymethyl cellulose blend based tubular electrospun scaffold for vascular tissue engineering

The present work deals with the fabrication of electrospun tubular scaffold based on in-situ crosslinked blend of gelatin - oxidized carboxymethyl cellulose (OCMC) for vascular tissue engineering. The flow behavior and spinability of the hydrogel despite the in-situ crosslinked gelatin chains evaluated by Raman spectroscopic studies and rheological studies was utilized for electrospinning. The study highlights the tunable pore size and fiber diameter of the nanofibers with the manipulation of electrospinning parameters. With a future perspective of vascular tissue engineering, the electrospinning parameters yielding smooth bead free fibers and maximum magnitude in pore size and fiber diameter as well their homogenous distribution were selected for the fabrication of tubular constructs which is rarely reported. The surface and mechanical properties were evaluated to validate its properties to the native vessel. Biocompatibility was studied in vitro with BALB/c 3T3 cells and in vivo after subcutaneous implantation in rats. MTT assay confirmed its no-toxicity and no abnormal foreign body reaction were observed by 7 and 15days after implantation. Crosslinking with biocompatible crosslinker OCMC has rendered insolubility to gelatin yet making it spinable for electrospinning to fabricate porous, nanofibrous vascular biomaterial.

Myocardial infarction and gut microbiota: An incidental connection

Myocardial infarction (MI) is the main cause of cardiovascular crises that entails serious concerns in mortality, morbidity, and cost to the society. The main therapeutic goal of modern cardiology is to develop novel approaches to minimize inflammation, myocardial necrosis/apoptosis, and enhance cardiac repair after MI. Though MI can be affected by genetic and environmental factors, the search for targeting lifestyle factors has been of greater interest. One such potential factor is the microbiota, the human intestinal microbial community. Although the fundamental data on the role of microbiome on MI is more limited, the disruption of intestinal flora structure provokes MI and poor prognosis. Since gut microbiota is readily modifiable through a variety of interventions, it can be targeted to modulate the host signaling pathways involved in inflammation and MI pathogenesis. Symbiosis bacteria can reduce ischemia/reperfusion injury and inflammation; moreover, they can regulate lipid metabolism, blood pressure, apoptosis, MI size, and overall cardiac survival. In this review, we provide an overview of the development of MI following the dysbiosis microbiota and give an update on a microbiota-based therapeutic strategy to delay or prevent MI.

Gadolinium/terbium hybrid macromolecular complexes for bimodal imaging of atherothrombosis

Abstract. We developed a fluorescence imaging microscope system intended for the localization within artery slices of a gadolinium-based macromolecular biospecific magnetic resonance (MR) contrast agent used for the visualization of atherothrombosis. As the contrast agent is not initially fluorescent, we substitute some gadolinium ions for terbium ions to make them fluorescent while preserving their chemical characteristics. A long fluorescence emission time constant enables us to have a suitable signal-to-noise ratio, despite a low intensity, using pulsed illumination and time-gated imaging. Images of rat arteries show that the contrast agent is indeed localized on the specific regions of the tissues. We currently have a tool that allows us to understand and optimize the MR contrast agent.

In vitro and in vivo hemocompatibility evaluation of a new dermatan sulfate‐modified PET patch for vascular repair surgery

The development of new vascular devices requires to study the effects of materials on blood cells and on coagulation, both in vitro and in vivo. In this study, we have developed a new material by grafting dermatan sulfate (DS) from shark skin onto polyethylene terephthalate (PET). We have evaluated the haemocompatibility of PET-DS material in vitro by measuring thrombin generation, plasma recalcification time, hemolytic activity, and platelet adhesion and in vivo with a model of vascular patch in rat abdominal aorta. In vitro, our results have shown that PET-DS is a nonhemolytic material, able to inhibit thrombin generation and platelet adhesion. In vivo studies by Doppler echographic evaluation 20 days after implantation have shown that the PET-DS patch was integrated in the vessel wall and covered by a layer of cells. In conclusion, PET-DS has good haemocompatibility properties and could be a promising tool for vascular surgery.