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See detailProtective effect of a new CHITOSAN BIOMATERIAL against the development of experimental osteoarthritis lesions in rabbit
Oprenyeszk, Frédéric ULg; Chausson, M; Maquet, V et al

Conference (2013, November 23)

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See detailThe intra-articular injection of alginate-chitosan beads in an hydrogel prevents the development of osteoarthritis in ACLT model
Oprenyeszk, Frédéric ULg; Chausson, M; Maquet, V et al

Conference (2013, September 16)

Purpose To evaluate the effects of a new biomaterial composed of alginate-chitosan (AC) beads dispersed in a viscous thermogelling chitosan-based (H) hydrogel on the development of osteoarthritis (OA) in ... [more ▼]

Purpose To evaluate the effects of a new biomaterial composed of alginate-chitosan (AC) beads dispersed in a viscous thermogelling chitosan-based (H) hydrogel on the development of osteoarthritis (OA) in rabbit. Materials & Methods OA was surgically induced by the transection of the anterior cruciate ligament (ACLT) in rabbits. One week after surgery, animals received a single intra-articular injection (900 µl) of AC beads in H hydrogel (group I), H hydrogel alone (group II) or saline (group III). OA development was followed by X-rays. Blood samples were collected throughout the study to measure biological markers (PGE2 and CRP). Macroscopic observation and histological evaluation of articular cartilage and synovial membrane were performed 6 weeks after surgery. Results The X-rays analysis showed a significant decrease (p <0.05) of the Kellgren and Lawrence score in group I (1.5 ± 0.2) compared with group II (2.2 ± 0.5) and group III (3.0 ± 0.4). The size and the severity of the macroscopic OA cartilage lesion tended to decrease in group I compared to the other groups. The histological global score that refers to all compartments of the knee joint was significantly decreased in group I (11.0 ± 0.7) compared to group II (14.4 ± 0.6, p <0.01) and group III (14.8 ± 0.6, p <0.001). The injection of AC beads in H hydrogel also tended to reduce the synovial membrane inflammation. No significant variation of PGE2 and CRP serum levels were observed in each after 6 weeks follow-up whatever the treatment injected. Conclusion This study showed that AC beads dispersed in H hydrogel prevented OA in ACL transection rabbit model. This effect was not observed with the hydrogel alone, suggesting that AC beads play a role in joint protection. The preventive effect was observed in all joint compartments indicating a global protective effect of this new implantable biomaterial. [less ▲]

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See detailProtective effect of a new biomaterial against the development of experimental osteoarthritis lesions in rabbit: a pilot study evaluating the intra-articular injection of alginate-chitosan beads dispersed in an hydrogel.
Oprenyeszk, Frédéric ULg; Chausson, Mickael; Maquet, Véronique et al

in Osteoarthritis and Cartilage (2013), 21(8), 1099-1107

Objective: This study aimed to evaluate the structural benefit of a new biomaterial composed of alginate-chitosan (AC) beads dispersed in an hydrogel (H) derived from chitosan on the development of ... [more ▼]

Objective: This study aimed to evaluate the structural benefit of a new biomaterial composed of alginate-chitosan (AC) beads dispersed in an hydrogel (H) derived from chitosan on the development of osteoarthritis (OA) in rabbit. Design: OA was induced by the surgical transection of the anterior cruciate ligament in rabbits. Animals received a single intra-articular injection (900 μl) of AC beads in H hydrogel, H hydrogel alone or saline one week after surgery. OA development was followed by X-rays. Blood samples were collected throughout the study to measure biological markers (PGE2 and CRP). Macroscopic observation and histological evaluation of articular cartilage and synovial membrane were performed 6 weeks after surgery. Results: AC beads in H hydrogel prevented from the development of OA based on the reduction of the Kellgren & Lawrence (K&L) score. It also significantly reduced the histological score of cartilage lesion severity. This effect was homogenous on every joint compartment. It was due to a significant effect on cartilage structure and cellularity scores. The injection of AC beads in H hydrogel also tended to reduce the synovial membrane inflammation. No significant variation of biological markers was noted. Conclusions: The present pilot study provides interesting and promising results for the use of AC beads in H hydrogel in animal. It indeed prevented the development of OA cartilage lesions without inflammatory signs. The potencies of this biomaterial to protect OA joint should be further documented. It could then represent a new alternative for viscosupplementation in human OA management. [less ▲]

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See detailThe intra-articular injection of a new chitosan biomaterial prevents the progression of osteoarthritis in ACLT rabbit model
Oprenyeszk, Frédéric ULg; Chausson, Mickael; Maquet, Véronique et al

in Osteoarthritis and Cartilage (2013, April), 21(Supplement April 2013), 69

Purpose To evaluate the effects of a single intra-articular injection of a new biomaterial consisting in a mix of alginate-chitosan (AC) beads and a viscous thermogelling chitosan-based (H) hydrogel on ... [more ▼]

Purpose To evaluate the effects of a single intra-articular injection of a new biomaterial consisting in a mix of alginate-chitosan (AC) beads and a viscous thermogelling chitosan-based (H) hydrogel on cartilage lesion in osteoarthritis (OA) rabbit model. These effects were compared to those obtained with the intra-articular injection of either chitosan-based (H) hydrogel without the AC bead or saline solution. Methods OA was surgically induced by the transection of the anterior cruciate ligament (ACLT) in HYLA albino rabbits. One week after surgery, animals were randomly divided into 3 groups: group I (n=7): mix of AC beads and H hydrogel; group II (n=7): H hydrogel alone; group III (n=7): saline solution (control). The treatments (900 µl) were injected intra-articularly. X-rays from the right knee were performed before surgery, at the time of injection and at sacrifice. The standard radiographs were acquired in extension and scored by the Kellgren and Lawrence (K&L) scale. After 6 weeks, animals were euthanized and the right joint was dissected. The macroscopic evaluation of cartilage from femoral condyles and tibial plateaus stained with India ink was done. Histological sections stained with Safranine-O/fast green from bearing areas of each compartment were evaluated according to the OARSI histological score. Briefly, the evaluation considered: staining of the cartilage matrix (0-6), cartilage structure (0-11), chondrocyte density (0-4) and cluster formation (0-3), where 0 represented a normal situation and 24 points the maximum severity score. Blood samples were collected the day of injection and prior the sacrifice. Prostaglandin E2 (PGE2) and C-reactive protein (CRP) were measured in serum using immunoassays. Results The X-rays analysis showed a significant decrease (p <0.05) of the K&L score in group I (AC beads and H hydrogel; 1.5 ± 0.2) compared with group II (H hydrogel; 2.2 ± 0.5) and group III (saline solution; 3.0 ± 0.4). The size and the severity of the macroscopic OA cartilage lesion tended to decrease in group I compared to the other groups. The histological global score that refers to all compartments of the knee joint was significantly decreased in group I (11.0 ± 0.7) compared to group II (14.4 ± 0.6, p <0.01) and group III (14.8 ± 0.6, p <0.001). No significant variation of PGE2 and CRP serum levels were observed in each after 6 weeks follow-up whatever the treatment injected. Conclusions This study showed that a biphasic hydrogel composed by AC beads and H hydrogel prevented OA in rabbit with ACL transection. This effect was not observed with the hydrogel alone, suggesting that AC beads play a role in joint protection. The preventive effect was observed in all joint compartments indicating a global protective effect of this new viscosupplementation. [less ▲]

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See detailAlginate-chitosan hydrogel beads decrease inflammatory and anabolic mediators produced by human chondrocytes
Oprenyeszk, Frédéric ULg; Sanchez, Christelle ULg; Dubuc, Jean-Emile et al

Poster (2012, September 17)

Introduction Osteoarthritis (OA) is the most prevalent arthritic disease. It is characterized by the degradation of articular cartilage accompanied by the inflammation of the synovial membrane and ... [more ▼]

Introduction Osteoarthritis (OA) is the most prevalent arthritic disease. It is characterized by the degradation of articular cartilage accompanied by the inflammation of the synovial membrane and sclerosis of subchondral bone. OA produces pain and loss of joint function. Today, there is no treatment to cure OA or to delay effectively its progression. Current treatments are mainly based on alleviation of painful symptoms but are unable to restore the cartilage. The development of new scaffold for tissue engineering is a promising approach. Herein, we report the effects of alginate-chitosan hydrogel (AC) beads on the metabolism of chondrocytes. Materials and Methods Human chondrocytes were isolated from OA cartilage and cultured either in AC beads or in alginate (A) beads. AC beads were prepared using chitosan (KiOmedine-CsU ultra-pure chitosan from KitoZyme, Herstal, Belgium) and alginate. The two polymer solutions were prepared separately before being mixed together. Cells were added to the polymer mixture and the cell-containing beads prepared by precipitation in a calcium chloride solution. The chondrocytes embedded in the beads were then cultured in a well defined culture medium for up to 28 days. Cell viability was determined by quantifying the release of lactate deshydrogenase (LDH) in the culture supernatant. Interleukin (IL)-6 and -8, prostaglandin E2 (PGE2), matrix metalloprotease (MMP)-3 and aggrecan were measured by specific ELISA. Finally, nitric oxide (NO) was measured by the Griess reaction. Results Histological analysis of AC beads showed chondrocytes in contact with chitosan trabeculae that were homogeneously distributed in the alginate matrix. LDH level remained below the limit of detection over the culture duration suggesting that AC had no cytotoxic effect. By comparison with culture in A beads, chondrocytes in AC beads produced significantly higher amounts of aggrecan but lowered the levels of MMP-3, NO, IL-6, IL-8 and PGE2. Discussion The contact between cells and AC beads components led us to hypothesize that chitosan has beneficial effects such as anti-inflammatory, anti-catabolic and stimulating effects on cartilage matrix components. Conclusion These particular effects indicate that AC beads are potentially new carriers for cell transplantation, particularly to repair cartilage defects. They could be further developed under various formulations, such as microbeads in combination with hydrogel for efficient viscossuplementation. [less ▲]

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See detailAdvances in biomaterials to repair cartilage
Maquet, Véronique; Chausson, Mickael; Gautier, Sandrine et al

Conference (2012, April 19)

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See detailL'injection intra-articulaire d'un biomatériau à base de chitosane prévient la progression de l'arthrose expérimentale induite par section du ligament croisé chez le lapin
Oprenyeszk, Frédéric ULg; Chausson, Mickael; Maquet, Véronique et al

in Revue du Rhumatisme (2012), 79(1), 108-109

Introduction La viscosupplémentation par injection intra-articulaire d’acide hyaluronique est recommandée dans le traitement de l’arthrose. Cependant, l’acide hyaluronique a une faible rémanence ... [more ▼]

Introduction La viscosupplémentation par injection intra-articulaire d’acide hyaluronique est recommandée dans le traitement de l’arthrose. Cependant, l’acide hyaluronique a une faible rémanence articulaire, ce qui limite son efficacité dans le temps. Dans ce travail, nous avons testé un nouveau biomatériau formé par le mélange de billes d’alginate-chitosane (AC) associées à un hydrogel visqueux synthétisé au départ de chitosane (H). Ce nouveau biomatériau breveté offre de nombreux avantages :1) biocompatible et non toxique, 2) composé exclusivement au départ de biopolymères d’origine non animale (chitosane et alginate), 3) les billes qui le composent sont élastiques, déformables et exercent un effet anti-inflammatoire et anti-catabolique sur les chondrocytes. Matériels et Méthodes L’arthrose a été induite chez le lapin HYLA albinos par la section du ligament croisé antérieur (LCA). Une semaine après l’intervention chirurgicale, les lapins ont été répartis dans trois groupes expérimentaux et ont bénéficié d’une injection intra-articulaire (900µl) des traitements suivants : billes AC associées à un hydrogel H (Groupe I ; n=7) ; hydrogel H seul (Groupe II ; n = 7) ; liquide physiologique (Groupe III ; n = 7). Des radiographies standards du genou en extension ont été réalisées avant l’intervention et pendant six semaines après l’intervention à raison d’une radiographie par semaine. Après 6 semaines de traitement, les animaux ont été euthanasiés et l’articulation prélevée. Une étude macroscopique du cartilage coloré à l’encre de Chine a été réalisée. Des coupes histologiques colorées à la Safranine-O/fast green provenant des zones portantes dans chaque compartiment ont été évaluées selon le score histologique de l’OARSI (Laverty et al., 2010). Résultats L’analyse des clichés radiologiques montrait une diminution significative (p<0,05) des signes radiologiques d’arthrose après 6 semaines dans le groupe I (billes AC + hydrogel H; 1,57 ± 0,2) en comparaison avec les groupe II (hydrogel H; 2,16 ± 0,47) et III (liquide physiologique ; 3,0 ± 0,43). La macroscopie révélait une tendance à l’amélioration de la taille et du grade des lésions dans le groupe I. La sévérité des lésions histologiques étaient significativement diminuée dans le groupe I (10,98 ± 0,72) par rapport au groupe II (14,43 ± 0,57 ; p<0,01) et au groupe III (14,79 ± 0,62 ; p<0,001). Cet effet était visible au niveau des condyles fémoraux et des plateaux tibiaux. Discussion L’injection intra-articulaire du mélange bille AC + hydrogel H est plus efficace que l’hydrogel H seul, ce qui suggère que les billes AC jouent un rôle dans l’efficacité de ce nouveau traitement. Cette nouvelle formulation pourrait être utilisée pour le traitement par viscosupplémentation de l’arthrose chez l’homme. Conclusion Le nouveau biomatériau formé par le mélange de billes AC et d’un hydrogel visqueux à base de chitosane prévient la progression de l’arthrose chez le lapin. [less ▲]

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See detailAn intra-articular supplementation method for treating joint diseases and injuries
Henrotin, Yves ULg; Sanchez, Christelle ULg; Oprenyeszk, Frédéric ULg et al

Patent (2011)

A method of producing a hydrogel for intra-articular supplement comprising the steps of: - providing a solution of alginate, - providing a solution with chitosan having a Mw between lower than 60 kD ... [more ▼]

A method of producing a hydrogel for intra-articular supplement comprising the steps of: - providing a solution of alginate, - providing a solution with chitosan having a Mw between lower than 60 kD, - mixing the solution of alginate and the solution of chitosan, wherein the mixed solution comprises between 0.5 and 0.7 % (w/v) of chitosan and between 1 and 1.4 % alginate (w/v), - introducing droplets of the mixed solution into a solution with Ca2+ or Sr2+ cations and - isolating polymerised beads from the solution with cations [less ▲]

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See detailLes billes alginate-chitosane : un nouveau biomatériau pour la réparation des lésions du cartilage
Oprenyeszk, Frédéric ULg; Sanchez, Christelle ULg; Dubuc, Jean-Emile et al

in Revue du Rhumatisme (2011), 78(suppl 5), 129-130

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See detailNew alginate-chitosan hydrogel beads with anti-inflammatory and anabolic effects on human chondrocytes
Oprenyeszk, Frédéric ULg; Sanchez, Christelle ULg; Dubuc, Jean-Emile et al

in Arthritis and Rheumatism (2011), 63(10), 697

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See detailNew alginate-chitosan hydrogel beads with anti-inflammatory and anabolic effects on human chondrocytes
Oprenyeszk, Frédéric ULg; Mathy, Marianne ULg; Sanchez, Christelle ULg et al

in Osteoarthritis and Cartilage (2011), 19(Suppl 1), 222

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