Impacts of maturation on the micromechanics of the meniscus extracellular matrix

Abstract

To elucidate how maturation impacts the structure and mechanics of meniscus extracellular matrix (ECM) at the length scale of collagen fibrils and fibers, we tested the micromechanical properties of fetal and adult bovine menisci via atomic force microscopy (AFM)-nanoindentation. For circumferential fibers, we detected significant increase in the effective indentation modulus, E, with age. Such impact is in agreement with the increase in collagen fibril diameter and alignment during maturation, and is more pronounced in the outer zone, where collagen fibrils are more aligned and packed. Meanwhile, maturation also markedly increases the E of radial tie fibers, but not those of intact surface or superficial layer. These results provide new insights into the effect of maturation on the assembly of meniscus ECM, and enable the design of new meniscus repair strategies by modulating local ECM structure and mechanical behaviors.

Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues

“…Consistent with this, our recent in vitro models exploring cell invasion into devitalized dense connective tissue (knee meniscus sections) showed reduced cellular invasion in adult tissues compared to less dense fetal tissues (3). The density of collagen in most adult dense connective tissues is 30 to 40 times higher than that used within in vitro collagen gel migration assay systems (2,3), emphasizing the substantial barrier to migration that the dense ECM plays in these tissues.…”

Influence of Fiber Stiffness on Meniscal Cell Migration into Dense Fibrous Networks

“…For example, the Young's moduli of the soft and stiff MeHA fibrous scaffolds (population of MeHA fibers, thickness of ≈134 µm) used in this study were previously determined through indentation testing to be ≈0.3 and ≈2.1 MPa, respectively . This is higher than measured values of juvenile bovine meniscus tissues (≈50 kPa), although it is difficult to compare these measurements and to understand the important mechanical properties in the cell microenvironment, particularly when they change over time with densification by cells. It should also be noted that mechanical loading of the scaffolds, which may occur upon implantation of a mechanically active tissues such as the meniscus, may also alter outcomes as this could influence parameters such as scaffold porosity.…”

“…For instance, the nuclei of adjacent host cells are often too large and too stiff to migrate through the small pores . Attenuated cell migration might also favor new tissue formation at the scaffold interface, which could further act as a barrier to hinder cell migration into scaffolds …”

Cell migration: implications for repair and regeneration in joint disease

“…Several age-related factors might exacerbate healing of adult joint tissues. During development, the collagen concentration and degree of collagen alignment in the ECM increase with load-bearing use of the joint, whereas endogenous cell density declines [103][104][105] , resulting in higher mechanical properties (such as the Young's modulus) on the microscale 47,105,106 and at bulk tissue level 107 . The compressive forces on the inner meniscus that occur during normal joint load bearing also lead to substantial accumulation of proteoglycans, most notably of aggrecan, with age [107][108][109] .…”

“…Collagen fibres: the mechanical properties of dense connective tissues are dictated by the concentration and organization of their ECM (primarily type I collagen, although type II collagen is also prevalent in articular cartilage and the inner region of the meniscus), such that the density and degree of alignment of collagen fibres correlate with increased tensile strength but decreased pore size that can impede migration 47,106 .…”