Structure-function relationships of fetal ovine articular cartilage

It is crucial that the properties of engineered neocartilage match healthy native cartilage to promote the functional restoration of damaged cartilage. To accurately assess the quality of neocartilage and the degree of biomimicry achieved, its properties must be evaluated against native cartilage and tissue from which the cells for neocartilage formation were sourced. Fetal ovine cartilage is a promising and translationally relevant cell source with which to engineer neocartilage, yet, it is largely non-characterized. The influence of biomechanics during cartilage development, as well as their potential impact on structure-function relationships in utero motivates additional study of fetal cartilage. Toward providing tissue engineering design criteria and elucidating structure-function relationships, 11 locations across four regions of the fetal ovine stifle were characterized. Locational and regional differences were found to exist. Although differences in GAG content were observed, compressive stiffness did not vary or correlate with any biochemical component. Patellar cartilage tensile stiffness and strength were significantly greater than those of the medial condyle. Tensile modulus and UTS significantly correlated with pyridinoline content. More advanced zonal organization, more intense collagen II staining, and greater collagen and pyridinoline contents in the trochlear groove and patella suggest these regions exhibit a more advanced maturational state than others. Regional differences in functional properties and their correlations suggest that structure-function relationships emerge in utero. These data address the dearth of information of the fetal ovine stifle, may serve as a repository of information for cartilage engineering strategies, and may help elucidate functional adaptation in fetal articular cartilage. STATEMENT OF SIGNIFICANCE: Engineered neocartilage must be evaluated against healthy native cartilage and cell source tissue to determine its quality and degree of biomimicry. While fetal ovine cartilage has emerged as a promising and translationally relevant cell source with which to engineer neocartilage, it is largely non-characterized. Therefore, 11 locations across four regions (medial condyle, lateral condyle, trochlear groove, and patella) of the fetal ovine stifle were characterized. Importantly, locational and regional differences in functional properties were observed, and significant correlations of tensile properties to collagen and crosslink contents were detected, suggesting that functional adaptation begins in utero. This study provides a repository of quantitative information, clarifies the developmental order of cartilage functional properties, and informs future cartilage engineering efforts.