Response of engineered cartilage tissue to biochemical agents as studied by proton magnetic resonance microscopy

Objective, To test the hypothesis that magnetic resonance imaging (MRI) res ults correlate with the biochemical composition of cartilage matrix and can therefore be used to evaluate natural tissue development and the effects o f biologic interventions. Methods. Chondrocytes harvested from day-16 chick embryo sterna were inocul ated into an MRI-compatible hollow-fiber bioreactor, The tissue that formed over a period of 2-4 weeks was studied biochemically, histologically, and with MRI. Besides natural development, the response of the tissue to admini stration of retinoic acid, interleukin-1 beta (IL-1 beta), and daily dosing with ascorbic acid was studied. Results. Tissue wet and dry weight, glycosaminoglycan (GAG) content, and co llagen content all increased with development time, while tissue hydration decreased. The administration of retinoic acid resulted in a significant re duction in tissue wet weight, proteoglycan content, and cell number and an increase in hydration as compared with controls. Daily dosing with ascorbic acid increased tissue collagen content significantly compared with control s, while the administration of IL-1 beta resulted in increased proteoglycan content. The water proton longitudinal and transverse relaxation rates cor related well with GAG and collagen concentrations of the matrix as well as with tissue hydration. In contrast, the magnetization transfer value for th e tissue correlated only with total collagen, Finally, the self-coefficient of water correlated with tissue diffusion hydration. Conclusion. Parameters derived from MR images obtained noninvasively can be used to quantitatively assess the composition of cartilage tissue generate d in a bioreactor. We conclude that MRI is a promising modality for the ass essment of certain biochemical properties of cartilage in a wide variety of settings.