Articular Cartilage Tissue Engineering
The clinical problem being investigated is how to treat defects in articular cartilage that can occur as a result of trauma, disease, or chronic mechanical loading imposed on joints with aging. Breakdown of articular cartilage leads to pain, instability, and swelling. Left untreated, a focal defect in articular cartilage can extend itself until it leads to degeneration of the entire joint and the need for total joint replacement. The current methods for treating such focal defects include microfracture, autologous chondrocyte implantation (ACI), and osteochondral autografting. However, these procedures have many shortcomings.
The goal of our work is to improve cartilage repair procedures by developing porous, absorbable collagen-glycosaminoglycan (CG) sponge-like scaffolds to be used alone or seeded with cells prior to implantation. We have shown in our own investigations that microfracture yields fibrocartilage and that ACI results in partial filling with hyaline cartilage (not articular cartilage) that breaks down by 12 months . We have demonstrated that the implantation of a collagen sponge-like scaffold in microfracture-treated sites increases the amount of reparative tissue in the defect, and that implantation of a chondrocyte-seeded CG scaffold results in more reparative tissue in a chondral defect when compared to ACI .
In our ongoing studies in vitro and in vivo, we are evaluating how the following variables affect cartilage repair:
1) the type of collagen used for the fabrication of the scaffolds (i.e., type I versus type II collagen);
2) the type of glycosaminoglycan used for the fabrication of the scaffolds;
3) methods for cross-linking the scaffolds;
4) the use of autologous mesenchymal stem cells instead of chondrocytes for seeding of the scaffolds prior to implantation;
5) growth factor supplementation of the serum-free medium in which the cell-seeded constructs are grown prior to implantation (Fig. 1);
6) incorporation of genes that encode for selected growth factors into the scaffolds; and
7) use of nanoparticles as delivery vehicles for genes.
Fig. 1. Light micrographs of articular canine chondrocytes seeded in type II collagen matrices after 2 weeks of culture in a) 10% fetal bovine serum control medium and b) serum-free medium to which 5 ng/ml of FGF-2 was added. Arrows in (b) show fragments of the original collagen-GAG scaffold. The tears in the histological sections were seen bordering the residual fragment occurred during microtomy. Safranin O/fast green stain.
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