Effects of intra‐articular hyaluronic acid associated to Chitlac (arty‐duo®) in a rat knee osteoarthritis model

Abstract

Among conventional osteoarthritis (OA) treatments, intra‐articular (i.a) viscosupplementation with hyaluronic acid (HA) is used to restore joint viscoelasticity. However, the rapid clearance and elimination of HA may limit its application. The aim of this study was to verify the improved efficacy of HA within the joint, using a lactose‐modified chitosan (chitlac) as a potentially chondroprotective additive. Four weeks after induction of experimental OA by destabilization of the medial meniscus (DMM), 12‐week‐old Sprague Dawley male rats (n = 30), received once a week, for three weeks, i.a injections of: (i) HA associated to chitlac (ARTY‐DUO®), (ii) HA; and (iii) sodium chloride (NaCl). Five animals for each group were euthanized 4 weeks after the first i.a injection, while the remaining five were euthanized 8 weeks after the first i.a injection. The restoration of physiological joint microenvironment was tested by histology, histomorphometry, immunohistochemistry, and microtomography (micro‐CT). At 4 and even more at 8 weeks, histological analysis showed a significant decrease in OARSI and Mankin scores, with weaker matrix metalloproteinase (MMP)‐3, MMP‐13, and Galectin‐3 in ARTY‐DUO® group versus NaCl and HA groups. A reduction in Galectin‐1 and a stronger Collagen II staining was seen in both ARTY‐DUO® and HA versus NaCl. A reduction in Kreen‐modified score, for synovium inflammation, was observed in the ARTY‐DUO® group. Micro‐CT measurements did not shown significant differences between the groups. The present results show that i.a ARTY‐DUO® injections produce a significant improvement in knee articular cartilage degeneration and synovium inflammation in a rat model of DMM‐induced OA. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Sodium Hyaluronate Supplemented Culture Media as a New hMSC Chondrogenic Differentiation Media-Model for in vitro/ex vivo Screening of Potential Cartilage Repair Therapies

“…Several studies proposed a beneficial effect of hMwt HA in tissue repair following injury or inflammation and the potential role of hyaluronic acid on the differentiation of hMSCs (Shinomura and Kimata, 1990;Jiang et al, 2007;Salamanna et al, 2019). Hypertrophy is one of the main problems related with MSC differentiation in exogenous TGF-β containing media (Johnstone et al, 1998;Goldring et al, 2006).…”

Boosting the Intra-Articular Efficacy of Low Dose Corticosteroid through a Biopolymeric Matrix: An In Vivo Model of Osteoarthritis

“…Recently, an in vivo study conducted by our group tested the infiltrative chondroprotective effects of HY associated to the anabolic properties of chitlac matrix (CTL) for knee OA. The study demonstrated that the combined administration of HY-CTL limits the development of lesions at the level of the articular cartilage, restoring the normal physiologic microenvironment and also limiting the alterations of the neighboring structures (i.e., the synovial membrane) [ 18 ]. Additionally, a reduction in galectin-1 and galectin-2 expression was seen in animals treated with HY-CTL [ 18 ].…”

Development of biodegradable membranes for the delivery of a bioactive chitosan‐derivative on cartilage defects: A preliminary investigation

“…The bioactive response induced in vitro by the polymer CTL in terms of enhancing the synthesis of collagen and GAGs in chondrocyte aggregates (Donati et al, ; Marsich et al, ) makes this modified polysaccharide an appealing choice to limit cartilage damage and favor the recovery of tissue functionality. A recent paper by Salamanna et al () evaluated preclinical therapeutic effects of intra‐articular injections of a formulation of CTL in mixture with hyaluronic acid (HA) on OA rat models; this study showed that the CTL‐based formulation caused a significant improvement in the treatment of knee‐articular cartilage degeneration and synovium inflammation as compared to HA‐treated and nontreated animals. Given these premises, materials based on CTL can be exploited as tools to deliver efficiently the bioactive polysaccharide at synovial site.…”