The knee joint is essential if an individual is to perform daily activities. This synovial joint connects the hip and ankle joints and allows motion of the lower extremity relative to the thigh. The knee joint has four articulating surfaces between the femur and the tibia. The ends of the bones are covered by a smooth layer of articular cartilage. The smooth articular surfaces, coupled with the lubricating characteristics of the synovial fluid, ensure low-friction movement in the joint. Knee joint stability is provided by different biological structures such as ligaments, menisci, and muscles which show multiplex biomechanical response and influence the articular cartilage behavior under different loading conditions [1,2]. In particular, ligaments and tendons provide firmness in more than one degree of freedom as well as restraining joint motion [3–5]. Research on knee ligament interactions and their effect on the cartilage mechanical response contributes to elucidating musculoskeletal disorders, injury mechanisms as well as improving rehabilitation protocols. Thus, during severe knee joint injuries, such as anterior cruciate ligament (ACL) rupture, other tissues in the joint such as the meniscus, cartilage, and other ligaments are also damage. ACL injury is a condition that generally affects the young and healthy population; ACL rupture leads to pain and instability and can predispose the subject to cartilage degeneration and post-traumatic osteoarthritis (PTOA) [6,7]. Unfortunately, there is a lack of convincing evidence that ACL reconstruction can prevent PTOA progression in the joint [8,9]. Alterations in the knee joint moments and contact forces during walking early after an ACL injury and reconstruction e.g. within 5 years of ACL injury, have demonstrated a linkage with the development of knee osteoarthritis (OA) [10,11].
PTOA is responsible for approximately $3 billion of health care costs in the United States annually [7,12]. Since it would be advantageous to reduce the socioeconomic impact and major health issues associated with PTOA after ACL injury, it would be highly desirable to develop better rehabilitation programs to minimize the risk of OA. However, effective strategies would require the identification of patients with an ACL injury who are most likely to develop PTOA and who would benefit from these kinds of interventions [13]. Currently, there are no clinical predictive tools which can identify patients early after ACL injury who are at a higher risk of developing post-traumatic OA [14]. The signs of PTOA include a PG loss from cartilage and surface disruption with lesions penetrating into the tissue [15].
Consequently, the fixed charge density (FCD) content and cartilage swelling decrease around the lesion, reducing the ability of the collagen network to support the tensile forces. However, the local adaptive and degenerative processes occurring in articular cartilage associated with these physiological changes remain unclear and are difficult to predict [13,16]. It has been suggested that local cartilage lesions might contribute to the development of PTOA following ACL injury and reconstruction [17].
Finite element (FE) models of the knee joint make it possible to investigate biomechanical responses of articular cartilage and other tissues under both normal and altered loading situations [18–21]. Similarly, in vitro mechanobiological models have been shown to be able to simulate tissue degeneration around cartilage lesions as a function of time [22–24]. The mechanisms leading to PTOA have been related to higher localized tissue stresses, strains (shear, deviatoric) or fluid flow around the lesions, especially to increase cell death and the consequential FCD loss [24,25].
Complementary, experimental studies have indicated that during early PTOA, the collagen content remains unaffected, but there may be other structural and compositional variations [26–28]. Moreover, other investigators have suggested that the FCD decrease appears before collagen damage with a short follow-up time [29,30]
and disorganization of the collagen network is almost negligible around cartilage defects [25]. However, the mechanisms leading to these structural changes remain unclear.
Magnetic resonance imaging (MRI) techniques are widely used in the analysis of early OA in the knee joint. Recent improvements in MRI techniques have made it possible to detect even changes in the biochemical composition in articular cartilage using T1ρ and T2 mapping sequences following an ACL injury and reconstruction [31–
34]. For example, recent investigations have revealed that T1ρ/T2 relaxation times increase after the ACL reconstruction surgery [35,36]. However, there are no studies that have compared MRI follow-up information of ACL reconstructed patients with the mechanobiological predictions of the progression of PTOA utilizing patient-specific knee joint models (including cartilage defects) and local adaptive algorithms.
Therefore, in this thesis, numerical knee joint models were developed for evaluating the effect of different ligament geometrical representations on the biomechanical response of the knee joint, especially on response of articular cartilage during the stance phase of gait (study I). Another aim was to develop and validate a cartilage degeneration algorithm based on experimental FCD measurements conducted in injured cartilage followed by a physiologically relevant dynamic compression. The FCD content at different follow-up time points was assessed using digital densitometry measurements. This degenerative algorithm was developed by implementing excessive deviatoric and maximum shear strain [24], as well as incorporating fluid velocity controlled mechanisms to simulate the FCD loss as a function of time (study II). Finally, the validated degenerative algorithm was implemented into three-dimensional (3D) patient-specific fibril-reinforced poroviscoelastic knee joint models to simulate alterations in the FCD content around cartilage lesions after an ACL injury and its subsequent reconstruction during the stance phase of the gait (study III).
The findings presented in this thesis contribute to understanding the development of OA after an injury to articular cartilage and the benefits of applying patient-specific mechanobiological models on the prediction of cartilage degradation. The developed methodologies can be utilized for simulating the effect
of surgical procedures and rehabilitation protocols on the early progression of PTOA.
These simulations can contribute to identifying optimal intervention protocols in order to slow down the progression of the disease and ultimately improving the quality of life of those people who suffer a knee injury.