L'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

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

The intra-articular injection of a new chitosan biomaterial prevents the progression of osteoarthritis in ACLT rabbit model

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

Non-clinical assessment of lubrication and free radical scavenging of an innovative non-animal carboxymethyl chitosan biomaterial for viscosupplementation: An in-vitro and ex-vivo study.

Lubrication and free radical scavenging are key features of biomaterials used for viscosupplementation (VS) of joints affected by osteoarthritis (OA). The objective of this study was to describe the non-clinical performance characterization of KiOmedine® CM-Chitosan, a non-animal carboxymethyl chitosan, in order to assess its intended action in VS and to compare it to existing viscosupplements based on crosslinked hyaluronan (HA) formulations.info:eu-repo/semantics/publishe

First-in-human Study to Evaluate a Single Injection of KiOmedine®CM-Chitosan for Treating Symptomatic Knee Osteoarthritis

Background: Single-injection viscosupplementation is currently performed with cross-linked hyaluronan (e.g. Durolane®) for treating symptomatic knee osteoarthritis. Objective: This first-in-human study evaluated the safety and performance of single-injection treatment with non-crosslinked KiOmedine®CM-Chitosan. Methods: Patients with painful knee osteoarthritis were randomly assigned to the KiOmedine®CM-Chitosan (n=63) or Durolane® (n=32) group. Patients were blinded to treatment and followed up for 26 weeks. Durolane® was used as scientific control to ensure the validity of the study and reliability of results. No direct comparison was performed between the two groups. The primary objective was defined as an intra-group effect size of 0.8 at 13 weeks post-injection compared to baseline on WOMAC-A (pain). Secondary outcomes included self-reported knee stiffness and knee function, responder rate, quality-of-life questionnaires, and safety. Results: The primary objective for both the KiOmedine®CM-Chitosan and the Durolane® groups was met: mean pain reduction of 62.5% (effect size 2.08) for the KiOmedine®CM-Chitosan group and 62.4% (effect size 2.28) for the Durolane® group. Secondary performance outcomes showed all clinically relevant treatment effects over 26 weeks for both groups (p<0.05). Treatment-related adverse events were more often reported in the KiOmedine®CM-Chitosan than Durolane® group and were limited to local reactions. No serious treatment-related adverse events were reported. Conclusion: A single intra-articular injection of non-crosslinked KiOmedine®CM-Chitosan is safe and effective for treating symptomatic knee osteoarthritis with a high responder rate. Pain reduction is maintained for 6 months with a high responder rate. The clinical trial registration number: NCT03679208.SCOPUS: ar.jinfo:eu-repo/semantics/publishe