Chondrocyte viability is lost during high-rate impact loading by transfer of amplified strain, but not stress, to pericellular and cellular regions

Abstract

Objective: Deleterious impact loading to cartilage initiates post-traumatic osteoarthritis (OA). While cytokine and enzyme levels regulate disease progression, specific mechanical cues that elucidate cellular OA origins merit further investigation. We defined the dominant pericellular and cellular strain/stress transfer mechanisms following bulk-tissue injury associated with cell death. Method: Using an in vitro model, we investigated rate-dependent loading and spatial localization of cell viability in acute indentation and time-course studies. Atomic force microscopy (AFM) and magnetic resonance imaging (MRI) confirmed depth-wise changes in cartilage micro-/macro-mechanics and structure post-indentation. To understand the transfer of loading to cartilage domains, we computationally modeled full-field strain and stress measures in interstitial matrix, pericellular and cellular regions. Results: Chondrocyte viability decreased following rapid impact (80%/s) vs slow loading (0.1%/s) or unloaded controls. Viability was lost immediately during impact within regions near the indenter-tissue contact but did not change over 7 days of tissue culture. AFM studies revealed a loss of stiffness following 80%/s loading, and MRI studies confirmed an increased tensile and shear strain, but not relaxometry. Image-based patterns of chondrocyte viability closely matched computational estimates of amplified maximum principal and shear strain in interstitial matrix, pericellular and cellular regions. Conclusion: Rapid indentation worsens chondrocyte death and degrades cartilage matrix stiffness in indentation regions. Cell death at high strain rates may be driven by elevated tensile strains, but not matrix stress. Strain amplification beyond critical thresholds in the pericellular matrix and cells may define a point of origin for early damage in post-traumatic OA.

Modeling early changes associated with cartilage trauma using human-cell-laden hydrogel cartilage models

“…The engineered cartilage constructs used in this study possess an elastic modulus of 30–40kPA and Young’s modulus of 196 ± 21 kPA by 28 days of in vitro differentiation. Upon traumatic loading with 30% strain, we observed a decrease in cell viability compared to that observed with impacts of similar rate and strain [ 37 , 38 ]. We also observed a loss on elastic modulus which seemed to be dependent on the encapsulated cells, inconsistent with decreased modulus of menisci and articular cartilage of PTOA lapine model [ 39 ].…”

Advances in organ-on-a-chip systems for modelling joint tissue and osteoarthritic diseases

“…Opportunities exist for integrating new mechanical, biochemical, and optical sensing technologies into JOC (and OOC) devices. For JOCs specifically, mechanical strain is a useful mechanical stimulus because it is a more reliable indicator of chondrocyte behaviour and viability than applied stress 74 . However, a JOC system capable of measuring applied forces on cartilage constructs and quantifying their mechanical properties has not yet been developed.…”

Radial Head Lag: A Possible Biomechanical Mechanism for Osteochondritis Dissecans of the Capitellum in Baseball Pitchers

“…This is a novel finding that we believe to be important in explaining the etiological mechanism responsible for OCD of the capitellum in baseball players. Repeated excessive shear stresses lead to cartilage damage 2,31 and to stress fractures in the subchondral bone, 32 which can result in nonunion under continued exposure to such stresses. The current consensus The relationship observed suggests that while most of the gap was created in the early stages of elbow extension, it continued to increase to a peak throughout extension.…”