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

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.

Controlled Release of Interleukin-1 Receptor Antagonist from Hyaluronic Acid-Chitosan Microspheres Attenuates Interleukin-1β-Induced Inflammation and Apoptosis in Chondrocytes

“…In our paper, we found that CS or HA-CS slightly but not significantly decreased NO 2 − , PGE2, and GAG, a finding consistent with previous investigations [27, 28]. The findings of the present study suggested that CS-IL-1Ra and HA-CS-IL-1Ra inhibited the production of inflammatory agents such as NO 2 − and PGE2, while decreasing the degradation of GAG induced by IL-1 β in chondrocytes.…”

Chitosan composite scaffolds for articular cartilage defect repair: a review

“…The research of Oprenyeszk et al 42 conrmed that the production of inammatory mediators IL-6 (p ¼ 0.0012), IL-8 (p < 0.0001), and PGE2 (p ¼ 0.0056) by chondrocytes was signicantly reduced by the addition of chitosan aer a 3 day culture. Furthermore, this signicant inhibitory effect was sustained during a culture period of 17-21 days.…”

Preliminary evaluation of an osteochondral autograft, a prosthetic implant, and a biphasic absorbable implant for osteochondral reconstruction in a sheep model

“…Chitosan is one of the most widely investigated polymers for regenerative medicine, in particular for cartilage regeneration because it displays structural properties that are similar to natural glycosaminoglycans . Chitosan promotes the expression of cartilage matrix compounds and reduces production of inflammatory and catabolic mediators by chondrocytes . A chitosan gel has been combined with microfracture to stabilize the blood clot and factors obtained from bone marrow stimulation, resulting in superior cartilage repair compared with microfracture alone up to 5 years postoperatively .…”

“…[18][19][20] Chitosan promotes the expression of cartilage matrix compounds and reduces production of inflammatory and catabolic mediators by chondrocytes. 21 A chitosan gel has been combined with microfracture to stabilize the blood clot and factors obtained from bone marrow stimulation, resulting in superior cartilage repair compared with microfracture alone up to 5 years postoperatively. 22 Hydroxypropylmethylcellulose (HPMC) provides a suitable environment for autologous stroma cells and chondrocytes 23 and induced cartilage formation with a hyaline-like organization in a rabbit cartilage defect model.…”