Articular cartilage tensile integrity: Modulation by matrix depletion is maturation-dependent

Abstract

Articular cartilage function depends on the molecular composition and structure of its extracellular matrix (ECM). The collagen network (CN) provides cartilage with tensile integrity, but must also remodel during growth. Such remodeling may depend on matrix molecules interacting with the CN to modulate the tensile behavior of cartilage. The objective of this study was to determine the effects of increasingly selective matrix depletion on tensile properties of immature and mature articular cartilage, and thereby establish a framework for identifying molecules involved in CN remodeling. Depletion of immature cartilage with guanidine, chondroitinase ABC, chondroitinase AC, and Streptomyces hyaluronidase markedly increased tensile integrity, while the integrity of mature cartilage remained unaltered after depletion with guanidine. The enhanced tensile integrity after matrix depletion suggests that certain ECM components of immature matrix serve to inhibit CN interactions and may act as modulators of physiological alterations of cartilage geometry and tensile properties during growth/maturation.

Effects of insulin-like growth factor 1 and basic fibroblast growth factor on the morphology and proliferation of chondrocytes embedded in Matrigel in a microfluidic platform

“…The physical, chemical and biological regulation of the cellular microenvironment is essential to maintain the spatial and temporal behavior of chondrocytes. Cartilage is avascular and aneural; thus, chondrocytes require nourishment by the slow diffusion of synovial fluid (12). Although the traditional two-dimensional (2D) cell culturing technique was typically adopted to explore the optimal expansion environment for chondrocytes in vitro, it remains controversial whether chondrocytes grown in vitro are morphologically identical to those present in vivo (13).…”

Tissue Engineering by Molecular Disassembly and Reassembly: Biomimetic Retention of Mechanically Functional Aggrecan in Hydrogel

“…Previous studies with cultured chondrocytes encapsulated in agarose have shown higher compressive stress with increasing sGAG content with time in culture. 30,50 Depletion of PG in immature cartilage has been shown to increase tensile strength 21 and may alter biomechanical properties in tissue-engineered constructs as well. 22 Studies of in vitro collagen fibril assembly have shown that the presence of PG, such as CS or AGC, alters size and rate of fibril formation and the mechanical properties of the resulting collagen-PG material as compared to collagen alone.…”

“…The samples were incubated with 1 mM 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride for 2 h at 378C to inhibit proteinase K and assayed using HA test kit (Corgenix). 21 HA was analyzed in PBS pooled from day 1 to 3, because the amount released was small in comparison to sGAG release as determined from a pilot study (Supplemental Material, available online at www.liebertonline.com/ten).…”

“…19,20 By modulating the assembly of aggregated PG, it may be possible to achieve the desired levels of PG components, which may modulate the mechanical properties of the engineered construct. 21,22 Additionally, the ability to accelerate the formation of PG aggregates in the engineered tissue has the potential to save a significant amount of time compared to the biological replenishment and redistribution of AGC. Thus, AGC may be a useful component to include during the assembly of cartilaginous constructs-alone, þHA, or þHAþLP.…”

Compaction Enhances Extracellular Matrix Content and Mechanical Properties of Tissue-Engineered Cartilaginous Constructs

“…In another method, selective enzymatic degradation of PG in cartilage and engineered constructs resulted in increased COL concentration, COL:PG ratio, and tensile stiffness of the tissue. [14][15][16] These approaches highlight the importance of the content of and balance between COL and PG in the mechanical function of tissue-engineered constructs. However, direct mechanical compaction to increase ECM concentration and mechanical function has not been studied previously.…”