Changes in mechanics and composition of human talar cartilage anlagen during fetal development

Abstract

Fetal cartilage anlage provides a framework for endochondral ossification and organization into articular cartilage. We previously reported differences between mechanical properties of talar cartilage anlagen and adult articular cartilage. However, the underlying development-associated changes remain to be established. Delineation of the normal evolvement of mechanical properties and its associated compositional basis provides insight into the natural mechanisms of cartilage maturation. Our goal was to address this issue. Human fetal cartilage anlagen were harvested from the tali of normal stillborn fetuses from 20 to 36 weeks of gestational age. Data obtained from stress relaxation experiments conducted under confined and unconfined compression configurations were processed to derive the compressive mechanical properties. The compressive mechanical properties were extracted from a linear fit to the equilibrium response in unconfined compression, and by using the nonlinear biphasic theory to fit to the experimental data from the confined compression experiment, both in stress-relaxation. The molecular composition was obtained using Fourier transform infrared (FTIR), and spatial maps of tissue contents per dry weight were created using FTIR imaging. Correlative and regression analyses were performed to identify relationships between the mechanical properties and age, compositional properties and age, and mechanical vs compositional parameters. All of the compositional quantities and the mechanical properties excluding the Poisson's ratio changed with maturation. Stiffness increased by a factor of ∼2.5 and permeability decreased by 20% over the period studied. Collagen content and degree of collagen integrity increased with age by ∼3-fold, while the proteoglycan content decreased by 18%. Significant relations were found between the mechanical and compositional properties. The mechanics of fetal talar cartilage is related to its composition, where the collagen and proteoglycan network play a prominent role. An understanding of the mechanisms of early cartilage maturation could provide a framework to guide tissue-engineering strategies.