Recently, nanometre-sized UHMWPE particles generated from hip and knee replacements have been identified in vitro and in vivo. UHMWPE particles in the 0.1-1.0μm size range have been shown to be more biologically active than larger particles, provoking an inflammatory response implicated in late aseptic loosening of total joint replacements. The biological activity of nanometre-sized particles has not previously been studied. The biological response to clinically-relevant UHMWPE wear particles including nanometre-sized and micrometre-sized, along with polystyrene particles (FluoSpheres 20nm, 60nm, 200nm and 1.0μm), and nanometre-sized model polyethylene particles (Ceridust 3615®), was determined in terms of osteolytic cytokine release from primary human peripheral blood mononuclear cells (PBMNCs). Nanometre-sized UHMWPE wear particles, nanometre-sized Ceridust 3615® and 20nm FluoSpheres had no significant effect on TNF-α, IL-1β, IL-6 and IL-8 release from PBMNCs at a concentration of 100μm(3) particles per cell after 12 and 24h. The micrometre-size UHMWPE wear particles (0.1-1.0μm) and 60nm, 200nm and 1.0μm FluoSpheres caused significantly elevated osteolytic cytokine release from PBMNCs. These results indicated that particles below circa 50nm fail to activate PBMNCs and that particle size, composition and morphology played a crucial role in cytokine release by particle stimulated macrophages.

The successful development of early-stage cartilage and meniscus repair interventions in the knee requires biomechanical and biotribological understanding of the design of the therapeutic interventions and their tribological function in the natural joint. The aim of this study was to develop and validate a porcine knee model using a whole joint knee simulator for investigation of the tribological function and biomechanical properties of the natural knee, which could then be used to pre-clinically assess the tribological performance of cartilage and meniscal repair interventions prior to in vivo studies. The tribological performance of standard artificial bearings in terms of anterior-posterior (A/P) shear force was determined in a newly developed six degrees of freedom tribological joint simulator. The porcine knee model was then developed and the tribological properties in terms of shear force measurements were determined for the first time for three levels of biomechanical constraints including A/P constrained, spring force semi-constrained and A/P unconstrained conditions. The shear force measurements showed higher values under the A/P constrained condition (predominantly sliding motion) compared to the A/P unconstrained condition (predominantly rolling motion). This indicated that the shear force simulation model was able to differentiate between tribological behaviours when the femoral and tibial bearing was constrained to slide or/and roll. Therefore, this porcine knee model showed the potential capability to investigate the effect of knee structural, biomechanical and kinematic changes, as well as different cartilage substitution therapies on the tribological function of natural knee joints.

A robust and stratified pre-clinical natural knee model, which has the capability to more appropriately simulate the biomechanical environment in vivo, will deliver more efficient and reliable assessment of soft tissue interventions before clinical studies. In order to simulate the biomechanical function of the natural knee without the natural ligaments in place, there is a requirement to develop appropriate spring constraints for the natural knee model. Therefore, this study was to investigate the effect of spring constraints on the function and output of the natural porcine knee model, and determine the spring constraint which most closely replicated the function of the natural ligaments. Two linear compression springs with stiffnesses of 9 N/mm (spring-9) and 20 N/mm (spring-20) were set at different free lengths in the anterior-posterior (A/P) axis in a natural knee simulator. The kinematic (A/P displacement) and tribological properties (shear force) output of the simulator were compared at different spring settings. The most appropriate spring setting was determined by comparing the A/P displacement and shear force output at different spring settings with those of the all ligaments model. Spring-9 with a free length of 4 mm showed the minimal difference (-0.03±0.68 mm) in A/P displacement output and spring-20 with a free length of 5 mm showed the minimal difference (-0.10±0.73 mm) in A/P displacement output compared to the all ligament control. There was no statistical difference between the two minimal differences either in A/P displacement or in shear force (paired t-test, p = 0.58, and p = 0.68 respectively) when both spring settings matched most closely to the A/P kinematics of the intact knee. This indicated that both conditions were appropriate spring constraints settings in the A/P direction for the natural porcine knee model.

It has recently been shown that the wear of ultra-high-molecular-weight polyethylene in hip and knee prostheses leads to the generation of nanometre-sized particles, in addition to micron-sized particles. The biological activity of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has not, however, previously been studied due to difficulties in generating sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene wear particles suitable for cell culture studies. In this study, wear simulation methods were investigated to generate a large volume of endotoxin-free clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles. Both single-station and six-station multidirectional pin-on-plate wear simulators were used to generate ultra-high-molecular-weight polyethylene wear particles under sterile and non-sterile conditions. Microbial contamination and endotoxin levels in the lubricants were determined. The results indicated that microbial contamination was absent and endotoxin levels were low and within acceptable limits for the pharmaceutical industry, when a six-station pin-on-plate wear simulator was used to generate ultra-high-molecular-weight polyethylene wear particles in a non-sterile environment. Different pore-sized polycarbonate filters were investigated to isolate nanometre-sized ultra-high-molecular-weight polyethylene wear particles from the wear test lubricants. The use of the filter sequence of 10, 1, 0.1, 0.1 and 0.015 µm pore sizes allowed successful isolation of ultra-high-molecular-weight polyethylene wear particles with a size range of < 100 nm, which was suitable for cell culture studies.

The successful development of cartilage repair treatments for the knee requires understanding of the biomechanical environment within the joint. Computational finite element models play an important role in non-invasively understanding knee mechanics, but it is important to compare model findings to experimental data. The purpose of this study was to develop a methodology for generating subject-specific finite element models of porcine tibiofemoral joints that was robust and valid over multiple different constraint scenarios. Computational model predictions of two knees were compared to experimental studies on corresponding specimens loaded under several different constraint scenarios using a custom designed experimental rig, with variations made to the femoral flexion angle and level of tibial freedom. For both in vitro specimens, changing the femoral flexion angle had a marked effect on the contact distribution observed experimentally. With the tibia fixed, the majority of the contact region shifted to the medial plateau as flexion was increased. This did not occur when the tibia was free to displace and rotate in response to applied load. These trends in contact distribution across the medial and lateral plateaus were replicated in the computational models. In an additional model with the meniscus removed, contact pressures were elevated by a similar magnitude to the increase seen when the meniscus was removed experimentally. Overall, the models were able to capture specimen-specific trends in contact distribution under a variety of different loads, providing the potential to investigate subject-specific outcomes for knee interventions.