Frédéric Oprenyeszk

Chitosan Enriched Three-Dimensional Matrix Reduces Inflammatory and Catabolic Mediators Production by Human Chondrocytes

This in vitro study investigated the metabolism of human osteoarthritic (OA) chondrocytes encapsulated in a spherical matrix enriched of chitosan. Human OA chondrocytes were encapsulated and cultured for 28 days either in chitosan-alginate beads or in alginate beads. The beads were formed by slowly passing dropwise either the chitosan 0.6%–alginate 1.2% or the alginate 1.2% solution through a syringe into a 102 mM CaCl2 solution. Beads were analyzed histologically after 28 days. Interleukin (IL)-6 and -8, prostaglandin (PG) E2, matrix metalloproteinases (MMPs), hyaluronan and aggrecan were quantified directly in the culture supernatant by specific ELISA and nitric oxide (NO) by using a colorimetric method based on the Griess reaction. Hematoxylin and eosin staining showed that chitosan was homogeneously distributed through the matrix and was in direct contact with chondrocytes. The production of IL-6, IL-8 and MMP-3 by chondrocytes significantly decreased in chitosan-alginate beads compared to alginate beads. PGE2 and NO decreased also significantly but only during the first three days of culture. Hyaluronan and aggrecan production tended to increase in chitosan-alginate beads after 28 days of culture. Chitosan-alginate beads reduced the production of inflammatory and catabolic mediators by OA chondrocytes and tended to stimulate the synthesis of cartilage matrix components. These particular effects indicate that chitosan-alginate beads are an interesting scaffold for chondrocytes encapsulation before transplantation to repair cartilage defects.

Development and evaluation in vitro and in vivo of injectable hydrolipidic gels with sustained-release properties for the management of articular pathologies such as osteoarthritis.

This study aimed to evaluate glycerol monooleate (GMO) as a carrier to develop viscoelastic and injectable sustained-release drug delivery systems. The potential pro- and antioxidant activity of the developed hydrolipidic gels were evaluated by measuring the production of ROS by polymorphonuclear leukocytes (PMNs). In addition, the biocompatibility and effectiveness of two selected gel candidates were evaluated in vivo by evaluating the benefit of a single intraarticular injection of these new treatments in a model of osteoarthritis in rabbits. The in vitro study demonstrated that the carrier F1 did not have a pro-oxidative effect and even protected PMNs against natural auto-activation, regardless of the incorporation of either clonidine chlorhydrate or betamethasone dipropionate. The in vivo study demonstrated that F1 and F1-BDP induced a loss of cartilage quality in comparison to the control and reference groups but that the lesions of cartilage observed were generally mild, with not much full-depth erosion. Moreover, no exacerbating inflammation was observed when considering the synovial membranes and the PGE2 and CRP levels. These results seemed to demonstrate that the sustained-release formulation based on GMO could be well-tolerated after intraarticular injection. Moreover, it could have the potential to prevent inflammatory conditions while sustaining drug activity locally over weeks.