Abstract
Osteoarthritis is a painful degenerative joint disease that could be better managed if tissue engineers can develop methods to create long-term engineered articular cartilage tissue substitutes. Many of the tissue engineered cartilage constructs currently available lack the chemical stimuli and cell-friendly environment that promote the matrix accumulation and cell proliferation needed for use in joint cartilage repair. The goal of this research was to test the efficacy of using a fibrin-alginate hydrogel containing hyaluronic acid (HA) and/or chondroitin sulphate (CS) supplements for chondrocyte culture. Neonatal porcine chondrocytes cultured in fibrin-alginate hydrogels retained their phenotype better than chondrocytes cultured in monolayer, as evidenced by analysis of their relative expression of type II versus type I collagen mRNA transcripts. HA or CS supplementation of the hydrogels increased matrix glycosaminoglycan (GAG) production during the first week of culture. However, the effects of these supplements on matrix accumulation were not additive and were no longer observed after two weeks of culture. Supplementation of the hydrogels with CS or a combination of both CS and HA increased the chondrocyte cell population after two weeks of culture. Statistical analysis indicated that the HA and CS treatment effects on chondrocyte numbers may be additive. This research suggests that supplementation with CS and/or HA has positive effects on cartilage matrix production and chondrocyte proliferation in three-dimensional (3D) fibrin-alginate hydrogels.
Highlights
Osteoarthritis is a term describing the erosion of or damage to articular cartilage, which, due to the inability of cartilage to naturally regenerate itself, poses a serious health concern to millions of people worldwide [1]
The effects of the hyaluronic acid (HA) and chondroitin sulphate (CS) treatments on GAG production were not additive, as hydrogels treated with both HA and CS in combination (HACS) were no higher in sulphated GAG accumulation than hydrogels supplemented with either HA or CS alone (Figure 1)
Numerous studies have shown that propagation of chondrocytes in monolayer cultures on standard tissue culture dishes leads to their gradual dedifferentiation, which is characterized by a switch from collagen II to collagen I synthesis, decreased aggrecan secretion and the adoption of a fibroblastic morphology [21]
Summary
Osteoarthritis is a term describing the erosion of or damage to articular cartilage, which, due to the inability of cartilage to naturally regenerate itself, poses a serious health concern to millions of people worldwide [1]. Cartilage tissue engineering is a discipline aimed at repairing articular cartilage lesions with artificial cartilage constructs. These constructs consist of a biocompatible three-dimensional (3D). Culture environment seeded with a suspension of chondrocytes or mesenchymal chondroprogenitor cells This culture environment provides initial mechanical support for the cells, as well as providing a micro-environment that supports cell proliferation and the maintenance or acquisition of a differentiated chondrocyte phenotype. These artificial cartilage constructs frequently have lower levels of extracellular matrix (ECM) relative to native cartilage [2]. This represents a critical consideration in engineered cartilage, as the mechanical properties of this neocartilage and its integration with the surrounding native cartilage is correlated with the level of ECM deposition [3,4]
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