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

Abstract

Objective 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. Materials and methods 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 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 versus compositional parameters. Results 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. Conclusion 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.

Foetal and postnatal equine articular cartilage development: magnetic resonance imaging and polarised light microscopy

“…Its dense appearance suggested enhanced collagen deposition and increased collagen content. A thin layer of higher collagen content has also been recently described in human AC foetal specimens (Mahmoodian et al, 2011). The surface birefringent layer we described, is also observed in new-born mice (Hughes et al, 2005) on PLM, but they were not assessed at the foetal stage.…”

“…MRI T2 relaxation times reflect the collagen fibril network's predominant structure (Goodwin and Dunn, 1998;Grunder et al, 1998;Mosher and Dardzinski, 2004;Nieminen et al, 2001;Nissi et al, 2006;Xia et al, 2001), the collagen content (Menezes et al, 2004;Mosher and Dardzinski, 2004) and also collagen-associated water (Mosher and Dardzinski, 2004;Nissi et al, 2006). The laminar appearance on T2-weighted images reflects the collagen orientation in the superficial zone (fibres parallel to the articular surface), transitional zone (random arrangement) and deep or radial zone (perpendicular to bone surface) (Xia et al, 2001).…”

Vibrational spectroscopy of articular cartilage

“…Assignments of NIR (80,84) and FTIR (19,39,50) proteoglycans than the native cartilage (20) and focal degenerative lesions in human osteoarthritic AC contained less proteoglycans than the surrounding healthy tissue (24). The univariate methods are easy to implement, and, therefore, they have been applied in many studies (25)(26)(27)(28)(29)(30)(31)(32). Collagen and proteoglycan concentration and collagen integrity maps produced using the univariate parameters in human tibial AC are shown in Figure 2.…”

Biomechanics of foetal movement

“…Mahmoodian et al (2009) reported that the talar cartilage of two foetuses between 30-32 weeks had a stiffness (aggregate modulus of 150 kPa) an order of magnitude lower than that of adult articular cartilage and permeability (2.01 × 10 -14 m 4 N -1 s -1 ) an order of magnitude greater than adult cartilage, suggesting that foetal cartilage is likely to deform and relax to larger extents than adult cartilage. In a follow-up study, Mahmoodian et al (2011) tested the mechanical properties of seven foetal talus anlagen over a range of gestational ages between 20 and 36 gestational weeks, and found that stiffness increased by a factor of roughly 2.5 (from 59.9 to 148 kPa), and permeability decreased by 20 % (from 2.64 × 10 -14 to 2.06 × 10 -14 m 4 N -1 s -1 ) over the age range studied. These changes in mechanical properties were associated with an increase in collagen content and integrity, and a decrease in proteoglycan content (Mahmoodian et al, 2011).…”

“…In a follow-up study, Mahmoodian et al (2011) tested the mechanical properties of seven foetal talus anlagen over a range of gestational ages between 20 and 36 gestational weeks, and found that stiffness increased by a factor of roughly 2.5 (from 59.9 to 148 kPa), and permeability decreased by 20 % (from 2.64 × 10 -14 to 2.06 × 10 -14 m 4 N -1 s -1 ) over the age range studied. These changes in mechanical properties were associated with an increase in collagen content and integrity, and a decrease in proteoglycan content (Mahmoodian et al, 2011). A study of the chondroepiphysis of the foetal proximal femur (Brown and Singerman, 1986) ) and Poisson's ratio than the aforementioned foetal talus studies (Mahmoodian et al, 2009;, which could reflect either differences in experimental design, differences between the properties of the two rudiments, or a combination of these factors.…”