Influence of the Mechanical Environment on the Regeneration of Osteochondral Defects

Abstract

Articular cartilage is a highly specialised connective tissue of diarthrodial joints which provides a smooth, lubricated surface for joint articulation and plays a crucial role in the transmission of loads. In vivo cartilage is subjected to mechanical stimuli that are essential for cartilage development and the maintenance of a chondrocytic phenotype. Cartilage damage caused by traumatic injuries, ageing, or degradative diseases leads to impaired loading resistance and progressive degeneration of both the articular cartilage and the underlying subchondral bone. Since the tissue has limited self-repairing capacity due its avascular nature, restoration of its mechanical properties is still a major challenge. Tissue engineering techniques have the potential to heal osteochondral defects using a combination of stem cells, growth factors, and biomaterials that could produce a biomechanically functional tissue, representative of native hyaline cartilage. However, current clinical approaches fail to repair full-thickness defects that include the underlying subchondral bone. Moreover, when tested in vivo, current tissue-engineered grafts show limited capacity to regenerate the damaged tissue due to poor integration with host cartilage and the failure to retain structural integrity after insertion, resulting in reduced mechanical function. The aim of this review is to examine the optimal characteristics of osteochondral scaffolds. Additionally, an overview on the latest biomaterials potentially able to replicate the natural mechanical environment of articular cartilage and their role in maintaining mechanical cues to drive chondrogenesis will be detailed, as well as the overall mechanical performance of grafts engineered using different technologies.

Keywords: articular cartilage; biomaterials; mechanical testing; mechanobiology; osteochondral defects; stem cells; tissue engineering.

Figure 1

Zonal architecture of articular cartilage and viscoelastic behaviour following compression. (A) Articular cartilage can be subdivided into 4 distinct zones: The superficial zone, the middle zone, the deep zone and the zone of calcified cartilage. Collagen fibre orientation in the extracellular matrix (ECM) and distribution of chondrocytes varies within each zone. (B) The ECM consists of a liquid phase (the interstitial fluid) and a solid phase composed of a type II collagen network interwoven with proteoglycans (predominantly aggrecan). The negative charge on the keratin sulphate and chondroitin sulphate glycosaminoglycans (GAGs) attracts positive ions that creates an osmotic pressure and retains water in the collagen network. When a compressive load is applied fluid flows out of the ECM in a time-dependent manner and similarly, when the load is removed, fluid is drawn back into the matrix restoring its original shape.

Figure 2

Schematic representation of the effect of physiological, overloading, and reduced loading on articular cartilage. Physiological loading is essential for maintaining cartilage homeostasis regulating ECM synthesis and chondrocytes proliferation. Overloading, caused by trauma, obesity and joint instability, reduces collagen, and aggrecan content inducing chondrocytes apoptosis. Reduced loading increase matrix degradation leading to cartilage thinning and softening.

Figure 3

Schematic representation of the mechanical cues affecting stem cell differentiation down the chondrogenic lineage. MSCs are mechanosensitive in response to ECM stiffness, dynamic loading, and hydrostatic pressures which activates various signalling pathways necessary to drive differentiation down the chondrocytic lineage.

Figure 4

Standard mechanical tests for assessing osteochondral grafts. Confined compression tests using either an impermeable chamber and porous indenter; or porous chamber with an impermeable indenter, are useful for defining the aggregate modulus. Unconfined compression tests and indentation tests can determine the elastic modulus (Young's modulus).