Walking on water: revisiting the role of water in articular cartilage biomechanics in relation to tissue engineering and regenerative medicine

Abstract

The importance, and the difficulty, of generating biosynthetic articular cartilage is widely recognized. Problems arise from obtaining sufficient stiffness, toughness and longevity in the material and integration of new material into existing cartilage and bone. Much work has been done on chondrocytes and tissue macromolecular components while water, which comprises the bulk of the tissue, is largely seen as a passive component; the 'solid matrix' is believed to be the main load-bearing element most of the time. Water is commonly seen as an inert filler whose restricted flow through the tissue is believed to be sufficient to generate the properties measured. We propose that this model should be turned on its head. Water comprises 70-80% of the matrix and has a bulk modulus considerably greater than that of cartilage. We suggest that the macromolecular components structure the water to support the loads applied. Here, we shall examine the structure and organization of the main macromolecules, collagen, aggrecan and hyaluronan, and explore how water interacts with their polyelectrolyte nature. This may inform the biosynthetic process by identifying starting points to enable developing tissue properties to guide the cells into producing the appropriate macromolecular composition and structure.

Keywords: aggrecan; cartilage; collagen; regenerative medicine; tissue engineering; water.

Figure 1.

Eleven hexapeptide repeats in the aggrecan sequence [70] (starting with glutamic acid (E)) are proposed to form an extended polyproline-II-like (threefold) helix. Each hexamer is then approximately 1.86 nm long. This indicates that the KS-chains, which form a twofold helix, all project on one side and their sulphates on alternate sides form a highly anionic plane of dimensions approximately 20 × 20 nm. KS-chain diagrams are adapted from diagrams published CC-BY by Selberg et al. [73].

Figure 2.

Schematic diagram, approximately to scale, showing hypothesized relationships between the hyaluronan-aggrecan complex and collagen fibrils. Aggrecans associate via their G1 globular domain along the HA molecule stabilized by LP. Assuming there is rotational flexibility, they can lie either side of the HA. This assembly then can lie along a portion of the collagen fibril leaving a gap between CS-regions of adjacent aggrecans of approximately the same dimensions as the fibril diameter. The KS-region of the aggrecan is localized to the gap region of the collagen and the KS chains all point in the same direction. The CS-regions (CS1 and CS2) then protrude into the inter-fibrillar space and have been shown extended although their conformation is unknown.

Figure 3.

Measurements, using X-ray diffraction, of the preferred orientation and orientation distribution function as a function of depth from the articular surface in human patellar cartilage. There are differences between views in (a) a medio-lateral direction and (b) a proximo-distal direction resulting in different apparent thicknesses of the surface, transition and deep zones. This is shown schematically in (c).