Mechanobiology of Cartilage Impact Via Real-Time Metabolic Imaging

Abstract

Cartilage loading is important in both structural and biological contexts, with overloading known to cause osteoarthritis (OA). Cellular metabolism, which can be evaluated through the relative measures of glycolysis and oxidative phosphorylation, is important in disease processes across tissues. Details of structural damage coupled with cellular metabolism in cartilage have not been evaluated. Therefore, the aim of this study was to characterize the time- and location-dependent metabolic response to traumatic impact loading in articular cartilage. Cartilage samples from porcine femoral condyles underwent a single traumatic injury that created cracks in most samples. Before and up to 30 min after loading, samples underwent optical metabolic imaging. Optical metabolic imaging measures the fluorescent intensity of byproducts of the two metabolic pathways, flavin adenine dinucleotide for oxidative phosphorylation and nicotinamide adenine dinucleotide ± phosphate for glycolysis, as well as the redox ratio between them. Images were taken at varied distances from the center of the impact. Shortly after impact, fluorescence intensity in both channels decreased, while redox ratio was unchanged. The most dramatic metabolic response was measured closest to the impact center, with suppressed fluorescence in both channels relative to baseline. Redox ratio varied nonlinearly as a function of distance from the impact. Finally, both lower and higher magnitude loading reduced flavin adenine dinucleotide fluorescence, whereas reduced nicotinamide adenine dinucleotide ± phosphate fluorescence was associated only with low strain loads and high contact pressure loads, respectively. In conclusion, this study performed novel analysis of metabolic activity following induction of cartilage damage and demonstrated time-, distance-, and load-dependent response to traumatic impact loading.