Postnatal changes to the mechanical properties of articular cartilage are driven by the evolution of its collagen network

Abstract

While it is well established that the composition and organisation of articular cartilage dramatically change during skeletal maturation, relatively little is known about how this impacts the mechanical properties of the tissue. In this study, digital image correlation was first used to quantify spatial deformation within mechanically compressed skeletally immature (4 and 8 week old) and mature (1 and 3 year old) porcine articular cartilage. The compressive modulus of the immature tissue was relatively homogeneous, while the stiffness of mature articular cartilage dramatically increased with depth from the articular surface. Other, well documented, biomechanical characteristics of the tissue also emerged with skeletal maturity, such as strain-softening and a depth-dependent Poisson's ratio. The most significant changes that occurred with age were in the deep zone of the tissue, where an order of magnitude increase in compressive modulus (from 0.97 MPa to 9.4 MPa for low applied strains) was observed from 4 weeks postnatal to skeletal maturity. These temporal increases in compressive stiffness occurred despite a decrease in tissue sulphated glycosaminoglycan content, but were accompanied by increases in tissue collagen content. Furthermore, helium ion microscopy revealed dramatic changes in collagen fibril alignment through the depth of the tissue with skeletal maturity, as well as a fivefold increase in fibril diameter with age. Finally, computational modelling was used to demonstrate how both collagen network reorganisation and collagen stiffening play a key role in determining the final compressive mechanical properties of the tissue. Together these findings provide a unique insight into evolving structure-function relations in articular cartilage.

Cell origin, volume and arrangement are drivers of articular cartilage formation, morphogenesis and response to injury in mouse limbs

“…It is only over postnatal life that the tissue grows in thickness and acquires its distinct zonal organization and cell columnar arrangement (Gannon et al, 2015; Julkunen et al, 2009), while the total number of cell layers remains about the same. How this transition occurs is a question that has vexed researchers for years.…”

Articular cartilage and joint development from embryogenesis to adulthood

“…While the tissue is highly cellular and isotropic at birth, unique zones develop as the tissue matures. This unique zonal architecture allows the articular cartilage to withstand significant shear and compressive forces throughout a joint's range of motion (Gannon et al, 2014; Helminen et al, 2000; Mienaltowski et al, 2008). At the surface adjacent to the joint cavity, the superficial zone is composed of elongated, flattened cells oriented parallel to the articular surface.…”

Transcriptome dynamics of long noncoding RNAs and transcription factors demarcate human neonatal, adult, and human mesenchymal stem cell‐derived engineered cartilage

“…Neonatal AC is functional but is not yet weight‐bearing and has not yet stratified into distinct functional zones like mature,adult AC(Brama, TeKoppele, Bank, Barneveld, & van Weeren, ; Brommer et al, ; Hunziker, Kapfinger, & Geiss, ). The cellular density of neonatal AC is much greater than in mature tissue, and it is primed to grow and expand as the body undergoes the rapid weight gain and increasing functional demands of early childhood development (Gannon, Nagel, Bell, Avery, & Kelly, ; Jadin, Bae, Schumacher, & Sah, ). A key result of this expansion and maturation takes the form of zone‐dependent collagen fibril organization and stiffening, which ultimately provide the tissue with its complex composite mechanical properties (Gannon et al, ).…”

“…The cellular density of neonatal AC is much greater than in mature tissue, and it is primed to grow and expand as the body undergoes the rapid weight gain and increasing functional demands of early childhood development (Gannon, Nagel, Bell, Avery, & Kelly, ; Jadin, Bae, Schumacher, & Sah, ). A key result of this expansion and maturation takes the form of zone‐dependent collagen fibril organization and stiffening, which ultimately provide the tissue with its complex composite mechanical properties (Gannon et al, ). The rapid pace of AC expansion in early development also raises the possibility that it may be the appropriate phenotype to alleviate another long‐standing issue in the field of AC grafting—failure of the graft tissue to integrate with the surrounding native tissue.…”