Abstract :
[en] 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.
