Shear strain and inflammation‐induced fixed charge density loss in the knee joint cartilage following ACL injury and reconstruction: A computational study

Abstract

Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient‐specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro‐inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage–synovial fluid‐interface and decreased toward the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a partial recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease‐modifying drug testing and rehabilitation strategies.

Injury-related cell death and proteoglycan loss in articular cartilage: Numerical model combining necrosis, reactive oxygen species, and inflammatory cytokines

“…Thus, we are planning to conduct additional experiments to validate our tissue-level model predictions which could then provide validated improvements in the current joint-level models [ 33 , 93 ]. One potential example could be merging this framework with musculoskeletal–finite element modeling workflow [ 33 , 94 , 95 ] which considers patient-specific joint geometry and loading. When adding inflammatory biomarkers from the synovial fluid, and possibly the defect size, to the workflow with our new cell-level mechanobiological model, virtual evaluation of the effects of biomechanical (such as rehabilitation) and biochemical (for example pharmaceutical treatment) interventions on cartilage health would become possible.…”

Site- and Zone-Dependent Changes in Proteoglycan Content and Biomechanical Properties of Bluntly and Sharply Grooved Equine Articular Cartilage

“… 1 Gene expression levels of inflammation markers interleukin-6 (IL-6) (week 23) and chemokine (C–C motif) ligand 2 (week 11 and 23) were elevated in synoviocytes from grooved joints compared to control joints (presented in our previous study 37 ). A recent mechanobiological computational modeling study 41 showed that the biochemical degeneration could cause superficial PG loss in the geometrically intact areas of grooved cartilage. Moreover, it should be noted that, in the tissue opposing the groove rim biomechanical factors may play a role as well, as the transition from contact to non-contact regions can cause higher local strains, and sliding may modulate mechanical wear and fatigue processes, as well as chondrocyte responses to joint loading.…”

Anterior Screw Insertion Results in Greater Tibial Tunnel Enlargement Rates after Single-Bundle Anterior Cruciate Ligament Reconstruction than Posterior Insertion: A Retrospective Study

“…During the healing process of graft and bone, inflammatory mediators are involved. These inflammatory mediators mainly enter the bone tunnel through synovial fluid [ 44 ]. After ACLR, higher concentrations of inflammatory factors are detected in the synovial fluid, including Interleukin-1β (IL-1β), IL-6, Tumor Necrosis Factor-α (TNF-α), nitric oxide (NO) [ 14 , 45 ], which can cause osteolysis [ 46 ].…”