Comparison between in vitro and in vivo cartilage overloading studies based on a systematic literature review.

Methodological differences between in vitro and in vivo studies on cartilage overloading complicate the comparison of outcomes. The rationale of the current review was to (i) identify consistencies and inconsistencies between in vitro and in vivo studies on mechanically-induced structural damage in articular cartilage, such that variables worth interesting to further explore using either one of these approaches can be identified; and (ii) suggest how the methodologies of both approaches may be adjusted to facilitate easier comparison and therewith stimulate translation of results between in vivo and in vitro studies. This study is anticipated to enhance our understanding of the development of osteoarthritis, and to reduce the number of in vivo studies. Generally, results of in vitro and in vivo studies are not contradicting. Both show subchondral bone damage and intact cartilage above a threshold value of impact energy. At lower loading rates, excessive loads may cause cartilage fissuring, decreased cell viability, collagen network de-structuring, decreased GAG content, an overall damage increase over time, and low ability to recover. This encourages further improvement of in vitro systems, to replace, reduce, and/or refine in vivo studies. However, differences in experimental set up and analyses complicate comparison of results. Ways to bridge the gap include (i) bringing in vitro set-ups closer to in vivo, for example, by aligning loading protocols and overlapping experimental timeframes; (ii) synchronizing analytical methods; and (iii) using computational models to translate conclusions from in vitro results to the in vivo environment and vice versa. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-11, 2018.

How a decreased fibrillar interconnectivity influences stiffness and swelling properties during early cartilage degeneration.

OBJECTIVE: The functional coupling between the fibrillar network and the high-swelling proteoglycans largely determines the mechanical properties of the articular cartilage matrix. The objective of this new study was to show specifically how changes in fibrillar interconnectivity arising from early cartilage degeneration influence transverse stiffness and swelling properties at the tissue level. DESIGN: Radial zone transverse layers of cartilage matrix were obtained from intact and mildly degenerate bovine patellae. Each layer was then subdivided to assess tensile stiffness, free-swelling response, glycosaminoglycan (GAG) content, and micro- and ultra-structural features. RESULTS: The tensile modulus was significantly lower and the degree of swelling significantly higher for the degenerate matrix compared to the intact. Scanning electron microscopy revealed a homogeneous response to transverse strain in the intact cartilage, whereas large non-fibrillar spaces between fibril aggregates were visible in the degenerate matrix. Although there were no significant differences in GAG content it did correlate significantly with stiffness and swelling in the intact samples but not in the degenerate. CONCLUSIONS: The lower degree of fibril network interconnectivity in the degenerate matrix led to both a decreased transverse stiffness and reduced resistance to osmotic swelling. This network 'de-structuring' also resulted in a reduced functional interaction between the fibrillar network and the proteoglycans. The study provides new insights into the role of the fibrillar network and how changes in the network arising from the degenerative cascade will influence tissue level behaviour.

How a radial focal incision influences the internal shear distribution in articular cartilage with respect to its zonally differentiated microanatomy.

Articular surface fibrillation and the loss of both transverse interconnectivity and zonal differentiation are indicators of articular cartilage (AC) degeneration. However, exactly how these structural features affect the load-redistributing properties of cartilage is still poorly understood. This study investigated how a single radial incision made to varying depths with respect to the primary zones of AC influenced its deformation response to compression. Three depths of incision were applied to cartilage-on-bone tissue blocks: one not exceeding the transition zone; one into the mid-radial zone; and one down to the calcified cartilage. Also included were non-incised controls. All samples were compressed to a near-equilibrium strain using a flat-faced indenter that incorporated a central relief channel within which the incision could be positioned lengthwise along the channel axis. Employing fixation under load followed by decalcification, the structural responses of the cartilage-on-bone samples were investigated. The study provides an analysis of the micro-morphological response that is characteristic of a completely normal cartilage-on-bone system but which contains a defined degree of disruption induced by the focal radial incision. The resulting loss of transverse continuity of the cartilage with respect to its zonally differentiated structure is shown to lead to an altered pattern of internal matrix shear whose intensity varies with incision depth.

How changes in fibril-level organization correlate with the macrolevel behavior of articular cartilage.

The primary structural components of articular cartilage are the zonally differentiated interconnected network of collagen fibrils and proteoglycans, the latter having the potential to bind large amounts of water. Both components exist in a coupled relationship that gives rise to its remarkable mechanical properties. The response of cartilage to compression is governed both by the degree to which the hydrated proteoglycans are constrained within this fibrillar network and the ease with which the matrix fluid can be displaced. The functional properties of cartilage are therefore closely linked to the integrity of the fibrillar network. Our current understanding of this network has been derived via studies conducted at the macro, micro, and ultrastructural levels. Of particular interest to joint researchers and clinicians are issues relating to how the network structure varies both directionally and with zonal depth, how its integrity is maintained via mechanisms of fibril interconnectivity, and how it is modified by ageing, degeneration, and trauma. Physical models have been developed to explore modes of interconnectivity. Combined micromechanical and structural studies confirm the critical role that this interconnectivity must play but detailed descriptions at the molecular level remain elusive. Current computationally based models of cartilage have in some cases implemented the fibrillar component, albeit simplistically, as a separate structure. Considering how important a role fibril network interconnectivity plays in actual tissue structure and mechanical behavior, and especially how it changes with degeneration, a major challenge facing joint tissue modellers is how to incorporate such a feature in their models.