Articular cartilage is the highly specialized connective tissue of diarthrodial joints. Its principal function is to provide a smooth, lubricated surface for articulation and to facilitate the transmission of loads with a low frictional coefficient (Figure 1). Articular cartilage is devoid of blood vessels, lymphatics, and nerves and is subject to a harsh biomechanical environment. Most important, articular cartilage has a limited capacity for intrinsic healing and repair. In this regard, the preservation and health of articular cartilage are paramount to joint health.



Figure 1.

Gross photograph of healthy articular cartilage in an adult human knee.



Injury to articular cartilage is recognized as a cause of significant musculoskeletal morbidity. The unique and complex structure of articular cartilage makes treatment and repair or restoration of the defects challenging for the patient, the surgeon, and the physical therapist. The preservation of articular cartilage is highly dependent on maintaining its organized architecture.

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The basic science of articular cartilage: structure, composition, and function

Forces in Joints, Skeletal Biology, Analysis of Bone Remodeling, Mechanical Properties of Bone, Fatigue and Fracture Resistance of Bone, Mechanical Adaptation of the Skeleton, Synovial Joint Mechanics, Mechanical Properties of Ligament and Tendon

Skeletal Tissue Mechanics

The extracellular matrix (ECM) may contribute to the drug resistance of a solid tumor by preventing the penetration of therapeutic agents. We measured differences in interstitial resistance to macromolecule (IgG) motion in four tumor types and found an unexpected correspondence between transport resistance and the mechanical stiffness. The interstitial diffusion coefficient of IgG was measured in situ by fluorescence redistribution after photobleaching. Tissue elastic modulus and hydraulic conductivity were measured by confined compression of excised tissue. In apparent contradiction to an existing paradigm, these functional properties are correlated with total tissue content of collagen, not glycosaminoglycan. An extended collagen network was observed in the more penetration-resistant tumors. Collagenase treatment of the more penetration-resistant tumors significantly increased the IgG interstitial diffusion rate. We conclude that collagen influences the tissue resistance to macromolecule transport, possibly by binding and stabilizing the glycosaminoglycan component of the ECM. These findings suggest a new method to screen tumors for potential resistance to macromolecule-based therapy. Moreover, collagen and collagen-proteoglycan bonds are identified as potential targets of treatment to improve macromolecule delivery.

https://cancerres.aacrjournals.org/content/canres/60/9/2497.full.pdf

Role of extracellular matrix assembly in interstitial transport in solid tumors.

Fluid transport and mechanical properties of articular cartilage: A review

Due to its avascular nature, articular cartilage exhibits a very limited capacity to regenerate and to repair. Although much of the tissue-engineered cartilage in existence has been successful in mimicking the morphological and biochemical appearance of hyaline cartilage, it is generally mechanically inferior to the natural tissue. In this study, we tested the hypothesis that the application of dynamic deformational loading at physiological strain levels enhances chondrocyte matrix elaboration in cell-seeded agarose scaffolds to produce a more functional engineered tissue construct than in free swelling controls. A custom-designed bioreactor was used to load cell-seeded agarose disks dynamically in unconfined compression with a peak-to-peak compressive strain amplitude of 10 percent, at a frequency of 1 Hz, 3 x (1 hour on, 1 hour off)/day, 5 days/week for 4 weeks. Results demonstrated that dynamically loaded disks yielded a sixfold increase in the equilibrium aggregate modulus over free swelling controls after 28 days of loading (100 +/- 16 kPa versus 15 +/- 8 kPa, p < 0.0001). This represented a 21-fold increase over the equilibrium modulus of day 0 (4.8 +/- 2.3 kPa). Sulfated glycosaminoglycan content and hydroxyproline content was also found to be greater in dynamically loaded disks compared to free swelling controls at day 21 (p < 0.0001 and p = 0.002, respectively).

Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels.

Biphasic Creep and Stress-Relaxation of Articular-Cartilage in Compression - Theory and Experiments

Analytical solutions have been obtained for the internal deformation and fluid-flow fields and the externally observable creep, stress relaxation, and constant strain-rate behaviors which occur during the unconfined compression of a cylindrical specimen of a fluid-filled, porous, elastic solid, such as articular cartilage, between smooth, impermeable plates. Instantaneously, the "biphasic" continuum deforms without change in volume and behaves like an incompressible elastic solid of the same shear modulus. Radial fluid flow then allows the internal fluid pressure to equilibrate with the external environment. The equilibrium response is controlled by the Young's modulus and Poisson's ratio of the solid matrix.

An analysis of the unconfined compression of articular-cartilage

The compressive viscoelastic behavior of articular cartilage, a fiber-reinforced, porous, permeable solid matrix filled with water, is predominately governed by the flow of the interstitial water within the tissue and its exudation across the articular surface. The fluid flow is in turn governed by the permeability of the tissue and the loading imposed upon its surface. But for articular cartilage, the permeability depends nonlinearly on the strain; k = ko exp (Me). Here, M is the nonlinear flow-limiting parameter and e is the dilatation. In this investigation, we studied the influence of M and Ro = koHA/Uh (where HA is the elastic equilibrium modulus of the solid matrix, h is the tissue's thickness and U is the rate of compression applied onto the surface via a rigid, porous, free-draining filter) on the stress history of circular plugs of cartilage specimens attached to the bone. It was found that these two parameters have profound effects on the predicted compressive stress history. For very large Ro, the fluid flow effects become negligible. For small Ro and large M, large instantaneous compressive stresses several times larger than those observed at equilibrium are predicted. This amplification of compressive stress is due to the increase of importance of the relative fluid flow effect, i.e., Ro leads to 0, and nonlinear flow-limit effect, i.e., M greater than 0. Also, the theoretical curves predict that the rate of increase of stress initially decreases (convex) and finally becomes a constant. The results of our 5 percent offset compression experiments are in good agreement with the theoretical predictions.

Effects of Nonlinear Strain-Dependent Permeability and Rate of Compression on the Stress Behavior of Articular Cartilage

Swelling of normal bovine articular cartilage equilibrated in NaCl solutions was dimensionally measured in thin strips of tissue. The ion-induced strains show that free swelling of articular cartilage is anisotropic and inhomogeneous. For the molar concentrations used, contraction increased linearly with concentration, defining a "coefficient of chemical contraction" (alpha c). Isometrically constrained specimens registered a rise in tensile force followed by stress relaxation. An extension of the biphasic theory incorporating this ion-induced strain is proposed. This theory can describe the equilibrium anisotropic swelling behavior of cartilage and explain the transient force history observed in the isometric experiment.

A Continuum Theory and an Experiment for the Ion-Induced Swelling Behavior of Articular Cartilage

The dominant mechanism giving rise to the viscoelastic response of articular cartilage during compression is the nonlinear diffusive interaction of the fluid and solid phases of the tissue as they flow relative to one another. The present study is concerned with the role of this interaction under uniaxial stress relaxation in compression. The model is a biphasic mixture of fluid and solid which incorporates the strain-dependent permeability found earlier from permeation experiments. When a ramp-displacement is imposed on the articular surface, simple, but accurate, asymptotic approximations are derived for the deformation and stress fields in the tissue for slow and moderately fast rates of compression. They are shown to agree very well with experiment and they provide a simple means for determining the material parameters. Moreover, they lead to important insights into the role of the flow-dependent viscoelastic nature of articular cartilage and other hydrated biological tissues.

W. M. Lai

Papers

Biphasic Creep and Stress-Relaxation of Articular-Cartilage in Compression - Theory and Experiments

An analysis of the unconfined compression of articular-cartilage

Effects of Nonlinear Strain-Dependent Permeability and Rate of Compression on the Stress Behavior of Articular Cartilage

A Continuum Theory and an Experiment for the Ion-Induced Swelling Behavior of Articular Cartilage

Singular Perturbation Analysis of the Nonlinear, Flow-Dependent Compressive Stress Relaxation Behavior of Articular Cartilage