Abstract
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.
Highlights
Osteoarthritis (OA) is a degenerative disease associated with many structural and functional disorders leading to the loss of joint integrity and function
The catabolic response is induced by pro-inflammatory mediators (e.g. interleukin (IL)-1, IL-8, IL6) and characterized by the overexpression of metalloproteinases (MMPs) including collagenases, stromelysin and tissue plasminogen activator, and by the production of prostaglandin (PG) E2 and nitric oxide (NO) [3]
TEM observation of chondrocytes embedded in CA beads
Summary
Osteoarthritis (OA) is a degenerative disease associated with many structural and functional disorders leading to the loss of joint integrity and function. It is the most prevalent form of arthritic disease in the world. It is mainly characterized by the slow progressive degeneration and the loss of articular cartilage accompanied by modification of the subchondral bone and synovial membrane inflammation [1]. The guidelines recommend a combination of non-pharmacological (i.e. exercises, orthoses, insoles, weight loss) and pharmacological modalities (e.g. NSAIDS, paracetamol) as the most effective strategy to manage pain and disability associated with OA [4,5,6,7,8,9,10]. Surgery, including arthroplasty, is recommended only as a last resort [5, 11]
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