Graciela Pavon-djavid | Université Sorbonne Paris Nord / Sorbonne Paris Nord University (original) (raw)

Papers by Graciela Pavon-djavid

Cells, 2021

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modali... more Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased numbe...

Biomedical Engineering / Biomedizinische Technik, 2017

Transcatheter aortic valve implantation (TAVI) has become a popular alternative technique to surg... more Transcatheter aortic valve implantation (TAVI) has become a popular alternative technique to surgical valve replacement for critical patients. Biological valve tissue has been used in TAVI procedures for over a decade, with over 150,000 implantations to date. However, with only 6 years of follow up, little is known about the long-term durability of biological tissue. Moreover, the high cost of tissue harvesting and chemical treatment procedures favor the development of alternative synthetic valve leaflet materials. In that context, textile polyester [polyethylene terephthalate (PET)] could be considered as an interesting candidate to replace the biological valve leaflets in TAVI procedures. However, no result is available in the literature about the behavior of textile once in contact with biological tissue in the valve position. The interaction of synthetic textile material with living tissues should be comparable to biological tissue. The purpose of this preliminary work is to com...

Journal of Materials Science: Materials in Medicine, 2011

Biomaterial surface properties, via alterations in the adsorbed protein layer, and the presence o... more Biomaterial surface properties, via alterations in the adsorbed protein layer, and the presence of specific functional groups can influence integrin binding specificity, thereby modulating cell adhesion and differentiation processes. The adsorption of fibronectin, a protein directly involved in osteoblast adhesion to the extracellular matrix, has been related to different physical and chemical properties of biomaterial surfaces. This study used blasting particles of different sizes and chemical compositions to evaluate the response of MG63 osteoblast-like cells on smooth and blasted titanium surfaces, with and without fibronectin coatings, by means of real-time reverse transcription-polymerase chain reaction (qRT-PCR) assays. This response included (a) expression of the a 5 , a v and a 3 integrin subunits, which can bind to fibronectin through the RGD binding site, and (b) expression of alkaline phosphatase (ALP) and osteocalcin (OC) as cell-differentiation markers. ALP activity and synthesis of OC were also tested. Cells on SiC-blasted Ti surfaces expressed higher amounts of the a 5 mRNA gene than cells on Al 2 O 3-blasted Ti surfaces. This may be related to the fact that SiC-blasted surfaces adsorbed higher amounts of fibronectin due to their higher surface free energy and therefore provided a higher number of specific cell-binding sites. Fn-coated Ti

Journal of Biomedical Materials Research, 2004

A major complication of intraocular lens surgery is diminished visual acuity caused by the regrow... more A major complication of intraocular lens surgery is diminished visual acuity caused by the regrowth of lens epithelial cells (secondary cataract). Polymethylmethacrylate (PMMA) is a commonly used intraocular lens material. This study addresses the mechanisms underlying the initial adhesion of lens epithelial cells to PMMA and a functionalized PMMA-based terpolymer known to inhibit cell proliferation. Rabbit lens epithelial cells were cultured on the test polymer surfaces in medium containing serum depleted of either fibronectin or vitronectin (or both) to identify the role of these proteins in the initial process of cell adhesion. Adherent cells were quantitated after 60 min, and the actin cytoskeleton and focal contact formation were compared in each serum treatment on both polymers. Vitronectin was significantly more effective for initial cell attachment to both polymers than fibronectin. Normal cell spreading on PMMA required vitronectin and was independent of fibronectin, whereas cell spreading on the terpolymer was abnormal and required the presence of fibronectin and vitronectin together. Together, these results help to explain the inhibition of cell proliferation previously shown on the functionalized PMMA. This work contributes to the design of a polymer for use in intraocular lenses that inhibits proliferation of the target cells.

IRBM, 2007

Dental implant-associated infections as peri-implantitis represent one of the major causes of ost... more Dental implant-associated infections as peri-implantitis represent one of the major causes of osteointegration failures of oral implants. Adhesion of Porphyromonas gingivalis, one of the bacterial strains mainly involved in such infections, is tightly dependent on the topographical and/or physico-chemical properties of the implant surfaces. As a matter of fact, we showed that the grafting of one bioactive polymer such as

Biomolecules

This work focuses on the development and evaluation of a dual nanostructured lipid carrier (NLC)/... more This work focuses on the development and evaluation of a dual nanostructured lipid carrier (NLC)/Carbopol®-based hydrogel system as a potential transporter for the topical delivery of curcumin to the skin. Two populations of different sized negatively charged NLCs (P1, 70–90 nm and P2, 300–350 nm) were prepared and characterized by means of dynamic light scattering. NLCs presented an ovoid platelet shape confirmed by transmission electron microscopy techniques. Curcumin NLC entrapment efficiency and release profiles were assessed by HPLC (high pressure liquid chromatography) and spectrophotometric methods. Preservation and enhancement of curcumin (CUR) antioxidant activity in NLCs (up to 7-fold) was established and cell viability assays on fibroblasts and keratinocytes indicated that CUR-NLCs are non-cytotoxic for concentrations up to 10 μM and exhibited a moderate anti-migration/proliferation effect (20% gap reduction). CUR-NLCs were then embedded in a Carbopol®-based hydrogel with...

Journal of Biomedical Optics, 2017

in the group Cardiovascular Bioengineering of Laboratory for Vascular Translational Science (LVTS... more in the group Cardiovascular Bioengineering of Laboratory for Vascular Translational Science (LVTS) who have synthesized the agents needed for my experiments. In the same laboratory Graciela Pavon-Djavid and Liliane Louedec were very kind with me too when they helped me preparing the samples from the rats arteries. I would like to thank my colleagues who are researchers in the departments of the Bichat Claude Bernard hospital: "Service Anatomie et Cytologie Pathologiques" and "Service de Radiologie et Imagerie Médicale". They helped me a lot when I tried the in vitro and in vivo experiments I would like to thank my colleagues in the Laboratoire de Physique des Lasers (LPL) where I worked most of the time, in particular the secretaries, mechanics and optics technicians for their assistance. Finally, I would like to thank the support and encouragement of my friends and my family, in particular my father, my mother and my wife.

Pharmaceutics, 2019

Natural antioxidants, such as astaxanthin (AX), resveratrol (RV) and curcumin (CU), are bioactive... more Natural antioxidants, such as astaxanthin (AX), resveratrol (RV) and curcumin (CU), are bioactive molecules that show a number of therapeutic effects. However, their applications are remarkably limited by their poor water solubility, physico-chemical instability and low bioavailability. In the present work, it is shown that self-assembled hyaluronan (HA)-based nanohydrogels (NHs) are taken up by endothelial cells (Human Umbilical Vein Endothelial Cells, HUVECs), preferentially accumulating in the perinuclear area of oxidatively stressed HUVECs, as evidenced by flow cytometry and confocal microscopy analyses. Furthermore, NHs are able to physically entrap and to significantly enhance the apparent water solubility of AX, RV and CU in aqueous media. AX/NHs, RV/NHs and CU/NHs systems showed good hydrodynamic diameters (287, 214 and 267 nm, respectively), suitable ζ-potential values (−45, −43 and −37 mV, respectively) and the capability to neutralise reactive oxygen species (ROS) in tube...

Marine Drugs, 2019

(1) Background: Reperfusion injury refers to the cell and tissue damage induced, when blood flow ... more (1) Background: Reperfusion injury refers to the cell and tissue damage induced, when blood flow is restored after an ischemic period. While reperfusion reestablishes oxygen supply, it generates a high concentration of radicals, resulting in tissue dysfunction and damage. Here, we aimed to challenge and achieve the potential of a delivery system based on astaxanthin, a natural antioxidant, in attenuating the muscle damage in an animal model of femoral hind-limb ischemia and reperfusion. (2) Methods: The antioxidant capacity and non-toxicity of astaxanthin was validated before and after loading into a polysaccharide scaffold. The capacity of astaxanthin to compensate stress damages was also studied after ischemia induced by femoral artery clamping and followed by varied periods of reperfusion. (3) Results: Histological evaluation showed a positive labeling for CD68 and CD163 macrophage markers, indicating a remodeling process. In addition, higher levels of Nrf2 and NQO1 expression in the sham group compared to the antioxidant group could reflect a reduction of the oxidative damage after 15 days of reperfusion. Furthermore, non-significant differences were observed in non-heme iron deposition in both groups, reflecting a cell population susceptible to free radical damage. (4) Conclusions: Our results suggest that the in situ release of an antioxidant molecule could be effective in improving the antioxidant defenses of ischemia/reperfusion (I/R)-damaged muscles.

Nutrition Reviews, 2019

Although chemotherapy succeeds in reducing tumor burden, the efficacy is limited due to acquired ... more Although chemotherapy succeeds in reducing tumor burden, the efficacy is limited due to acquired drug resistance and often irreparable side effects. Studies show that antioxidants may influence the response to chemotherapy and its side effects, although their use remains controversial. The evidence shows that some chemo-drugs induce oxidative stress and lead to normal tissue apoptosis and the entry of cancer cells to a dormant G0 state. Through the suppression of oxidative stress, antioxidants could protect normal cells and bring the tumor out of dormancy so as to expose it to chemotherapies. This review is focused on the redox biology of cancer/normal cells and association of reactive oxygen species with drug resistance, cancer dormancy, and side effects. To this end, evidence from cellular, animal, and clinical studies is provided to better understand the conundrum of dietary antioxidants in cancer chemotherapy.

Iranian Red Crescent Medical Journal, 2018

Background: microRNAs (miRNAs) are endogenous gene expression regulators, which are involved in t... more Background: microRNAs (miRNAs) are endogenous gene expression regulators, which are involved in the physiopathology of diseases, and potentially make biomarkers in diseases, such as Cardiovascular Disease (CVD). Objectives: Since miR-21 is a robust regulator in plaque formation, this study aimed at identifying the effect of saffron as a functional food and traditional food additive antioxidant in fighting against the progress of atherosclerosis, by modulation of miR-21, as a new circulating marker of inflammation. Methods: In this randomized, double-blind clinical trial, 63 subjects with atherosclerosis were recruited from Emam Sajjad Hospital, Valiasr Hospital, and Zafaranieyh Clinic in Tehran, Iran, and divided randomly to two groups. They received 100 mg/d saffron or a placebo capsule for six weeks. The expression levels of miR-21 were quantified by real-time quantitative-PCR (RT-qPCR) in the blood of patients. Furthermore, fasting blood sugar, lipid profile, and anthropometric index of participants were evaluated before and after the intervention. Results: Statistical analysis showed significant differences in the expression level of miR-21 between atherosclerosis patients, who received placebo, and those, who consumed saffron (P value = 0.02). Moreover, a significant decrease was seen in hip circumference after saffron supplementation (P = 0.049, P = 0.006). Nevertheless, consumption of saffron did not significantly influence other anthropometric indexes and blood biochemical parameters, such as FBS and lipid profile. Conclusions: In the present study, different expression levels of miR-21 were observed between patients with atherosclerosis, who received saffron supplements and placebo; thus saffron may be considered as a novel therapeutic target in cardiovascular disease management.

Polymer International, 2019

The work involves the fabrication of electrospun tubular conduit of gelatin and polycaprolactone ... more The work involves the fabrication of electrospun tubular conduit of gelatin and polycaprolactone (PCL) blend as an adventitia equivalent construct. Gelatin has been included as the matrix for increased biocompatibility with the addition of PCL for durability. This is contrary to most of the literature available for biomaterials based on the blend of gelatin and PCL where PCL is the major matrix. The work includes the assiduous selection of key electrospinning parameters to obtain smooth bead free fibers with a narrow distribution of pore size and fiber diameter. Seldom reports elucidate the optimization of all electrospinning parameters to fabricate tubular conduits with a focus of obtaining homogenous pores and fibers. This step-wise investigation would be unique for the fabrication of gelatin-PCL electrospun tubular construct. The fabricated microfibrous gelatin-PCL constructs had pores of size ~50-100 µm reportedly conducive for cell infiltration. The measured value of surface roughness of 57.99 ± 17.4 nm is reported to be favorable for protein adhesion and cell adhesion. The elastic modulus was observed to be in resemblance to the tunica adventitia of the native artery. Preliminary in-vitro and in-vivo biocompatibility tests suggest its safe applicability as a biomaterial. Minimal cytotoxicity was observed using the MTT assay. Subcutaneous implantation of the scaffold demonstrated acute inflammation which decreased by day 15. This study could enable the fabrication of smooth bead-free This article is protected by copyright. All rights reserved. microfibrous gelatin-PCL tubular constructs as a viable biomaterial which can be included in a bilayer or a trilayer scaffold for vascular tissue engineering.

Chemico-Biological Interactions, 2018

Oxidative stress induced by Reactive Oxygen Species (ROS) was shown to be involved in the pathoge... more Oxidative stress induced by Reactive Oxygen Species (ROS) was shown to be involved in the pathogenesis of chronic diseases such as cardiovascular pathologies. Particularly, oxidative stress has proved to mediate abnormal platelet function and dysfunctional endothelium-dependent vasodilatation representing a key factor in the progression of ischemic injuries. Antioxidants like carotenoids have been suggested to contribute in their prevention and treatment. Astaxanthin, a xanthophyll carotenoid produced naturally and synthetically, shows interesting antioxidant and anti-inflammatory properties. In vivo studies applying different models of induced ischemia and reperfusion (I/R) injury confirm astaxanthin's protective action after oral or intravenous administration. However, some studies have shown some limitations after oral administration such as low stability, bioavailability and bioefficacy, revealing a need for the implementation of new biomaterials to act as astaxanthin vehicles in vivo. Here, a brief overview of the chemical characteristics of astaxanthin, the carrier systems developed for overcoming its delivery drawbacks and the animal studies showing its potential effect to treat I/R injury are presented.

Food Chemistry, 2018

green supramolecular solvents for cost-effective production of highly stable astaxanthin-rich for... more green supramolecular solvents for cost-effective production of highly stable astaxanthin-rich formulations from Haematococcus pluvialis, Food Chemistry (2018), doi:

International journal of biological macromolecules, Jan 12, 2017

The present work deals with the fabrication of electrospun tubular scaffold based on in-situ cros... more 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 a...

Biomedical Materials, 2017

After myocardial infarction, the heart's mechanical properties and its intrinsic capability t... more After myocardial infarction, the heart's mechanical properties and its intrinsic capability to recover are compromised. To improve this recovery, several groups have developed cardiac patches based on different biomaterials strategies. Here, we developed polyvinylalcohol/dextran (PVA/Dex) elastic hydrogel patches, obtained through the freeze thawing (FT) process, with the aim to deliver locally a potent natural antioxidant molecule, astaxanthin, and to assist the heart's response against the generated myofibril stress. Extensive rheological and dynamo-mechanical characterization of the effect of the PVA molecular weight, number of freeze-thawing cycles and Dex addition on the mechanical properties of the resulting hydrogels, were carried out. Hydrogel systems based on PVA 145 kDa and PVA 47 kDa blended with Dex 40 kDa, were chosen as the most promising candidates for this application. In order to improve astaxanthin solubility, an inclusion system using hydroxypropyl-β-cyclodextrin was prepared. This system was posteriorly loaded within the PVA/Dex hydrogels. PVA145/Dex 1FT and PVA47/Dex 3FT showed the best rheological and mechanical properties when compared to the other studied systems; environmental scanning electron microscope and confocal imaging evidenced a porous structure of the hydrogels allowing astaxanthin release. In vitro cellular behavior was analyzed after 24 h of contact with astaxanthin-loaded hydrogels. In vivo subcutaneous biocompatibility was performed in rats using PVA145/Dex 1FT, as the best compromise between mechanical support and astaxanthin delivery. Finally, ex vivo and in vivo experiments showed good mechanical and compatibility properties of this hydrogel. The obtained results showed that the studied materials have a potential to be used as myocardial patches to assist infarcted heart mechanical function and to reduce oxidative stress by the in situ release of astaxanthin.

Cardiovascular Pathology, 2017

Background: In-stent neoatherosclerosis is characterized by the delayed appearance of markers of ... more 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 instent 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.

Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2016

The development of new vascular devices requires to study the effects of materials on blood cells... more 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. V