Immunohistochemical study of collagen types I and II and procollagen IIA in human cartilage repair tissue following autologous chondrocyte implantation

Abstract

This study has assessed the relative proportions of type I and II collagens and IIA procollagen in full depth biopsies of repair tissue in a large sample of patients treated with autologous chondrocyte implantation (ACI). Sixty five full depth biopsies were obtained from knees of 58 patients 8–60 months after treatment by ACI alone (n = 55) or in combination with mosaicplasty (n = 10). In addition articular cartilage was examined from eight individuals (aged 10–50) as controls. Morphology and semi-quantitative immunohistochemistry for collagen types I and II and procollagen IIA in the repair tissue were studied. Repair cartilage thickness was 2.89 ± 1.5 mm and there was good basal integration between the repair cartilage, calcified cartilage and subchondral bone. Sixty five percent of the biopsies were predominantly fibrocartilage (mostly type I collagen and IIA procollagen), 15% were hyaline cartilage (mostly type II collagen), 17% were of mixed morphology and 3% were fibrous tissue (mostly type I collagen). Type II collagen and IIA procollagen were usually found in the lower regions near the bone and most type II collagen was present 30–60 months after treatment. The presence of type IIA procollagen in the repair tissue supports our hypothesis that this is indicative of a developing cartilage, with the ratio of type II collagen:procollagen IIA increasing from < 2% in the first two years post-treatment to 30% three to five years after treatment. This suggests that cartilage repair tissue produced following ACI treatment, is likely to take some years to mature.

Use of Collagen Scaffold and Autologous Bone Marrow Concentrate as a One-Step Cartilage Repair in the Knee: Histological Results of Second-Look Biopsies at 1 Year Follow-up

“…Only a few studies have investigated the histological appearance of ACI biopsies (12)(13)(14)(15)(16)(17)(18) and an even lower number have looked for clinical and histological outcomes of one-step procedures (10,19) in the treatment of articular cartilage lesions.…”

Mechanical confinement regulates cartilage matrix formation by chondrocytes

“…However, each of these treatments have had limited success over the long-term. Formation of fibrocartilage instead of articular cartilage is a well-known issue associated with ACI 7 , MACI 7 , and microfracture 8 , with fibrocartilage impairing joint function, while allografts carry the risk of disease transmission from the donor 6 .…”

A case study: Glycosaminoglycan profiles of autologous chondrocyte implantation (ACI) tissue improve as the tissue matures

“…For cartilage repair tissue, there have been many studies assessing the collagen [28][29][30] but a very limited number of studies assessing proteoglycans and GAGs. Proteoglycans, with their associated highly anionic GAGs, are key players in a range of cartilage functions including tissue compressibility, tissue remodelling, up-take of proteins, intracellular signalling and cell movement 31 .…”

“…Furthermore, CS chains were significantly shorter in 12 month ACI repair tissue 8 . Many studies have reported on maturation of chondrocytes in pellets 31 and cartilage like tissue in scaffolds 32 but very few studies have reported on tissue maturation within a cartilage defect 11,12,29 .…”