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

Rheological Equations for Synovial Fluids

We demonstrate a capillary device used to measure the shear rate-dependent viscosity of microliter scale volumes. Liquid samples are driven pneumatically through a microcapillary and partially fill a larger glass capillary. The glass capillary is mounted on an optical linear sensor to track the air-liquid meniscus in real time and trigger the reversal of flow direction by switching a pneumatic valve. Each transit provides a volumetric flow rate measurement, which is used with the pressure drop to determine viscosity as a function of shear rate. A given sample of at least 50 µL can be measured over at least 2 to 3 decades in shear rate, in the range of 10 to $$10^5$$ $${\mathrm{s}}^{-1}$$ , and be essentially fully recovered. Validation by comparison to reference measurements is performed using samples of Newtonian and non-Newtonian fluid, with viscosity ranging from 1 to 100 mPa s. The range of operation and uncertainty arising from instrumentation, meniscus effects, and inertial effects are discussed. The performance of this rheometer is advantageous, especially for use and reuse of small volumes. 

A small-volume microcapillary rheometer

Semiflexible filaments deform into a variety of configurations that dictate different phenomena manifesting at low Reynolds number. Harnessing the elasticity of these filaments to perform transport-related processes at the microfluidic scale requires structures that can be directly manipulated to attain controllable geometric features during their deformation. The configuration of semiflexible chains assembled from paramagnetic colloids can be readily controlled upon the application of external time-varying magnetic fields. In circularly rotating magnetic fields, these chains undergo coiling dynamics in which their ends close into loops that wrap inward, analogous to the curling of long nylon filaments under shear. The coiling is promising for the precise loading and targeted transport of small materials, however effective implementation requires an understanding of the role that field parameters and chain properties play on the coiling features. Here, we investigate the formation of coils in semiflexible paramagnetic chains using numerical simulations. We demonstrate that the size and shape of the initial coils are governed by the Mason and elastoviscous numbers, related to the field parameters and the chain bending stiffness. The size of the initial coil follows a nonmonotonic behavior with Mason number from which two regions are identified: (1) an elasticity-dependent nonlinear regime in which the coil size decreases with increasing field strength and for which loop shape tends to be circular, and (2) an elasticity-independent linear regime where the size increases with field strength and the shape become more elliptical. From the time scales associated to these regimes, we identify distinct coiling mechanisms for each case that relate the coiling dynamics to two other configurational dynamics of paramagnetic chains: wagging and folding behaviors.

S. C. Kuei

Papers

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

Rheological Equations for Synovial Fluids

A small-volume microcapillary rheometer

Coiling of semiflexible paramagnetic colloidal chains.