IL-1 and iNOS gene expression and NO synthesis in the superior region of meniscal explants are dependent on the magnitude of compressive strains

OBJECTIVE: Partial meniscectomy is known to cause osteoarthritis (OA) of the underlying cartilage as well as alter the load on the remaining meniscus. Removal of 30-60% of the medial meniscus increases compressive strains from a maximum of approximately 10% to almost 20%. The goal of this study is to determine if meniscal cells produce catabolic molecules in response to the altered loading that results from a partial meniscectomy. METHOD: Relative changes in gene expression of interleukin-1 (IL-1), inducible nitric oxide synthase (iNOS) and subsequent changes in the concentration of nitric oxide (NO) released by meniscal tissue in response to compression were measured. Porcine meniscal explants were dynamically compressed for 2 h at 1 Hz to simulate physiological stimulation at either 10% strain or 0.05 MPa stress. Additional explants were pathologically stimulated to either 0% strain, 20% strain or, 0.1 MPa stress. RESULTS: iNOS and IL-1 gene expression and NO release into the surrounding media were increased at 20% compressive strain compared to other conditions. Pathological unloading (0% compressive strain) of meniscal explants did not significantly change expression of IL-1 or iNOS genes, but did result in an increased amount of NO released compared to physiological strain of 10%. CONCLUSION: These data suggest that meniscectomies which reduce the surface area of the meniscus by 30-60% will increase the catabolic activity of the meniscus which may contribute to the progression of OA

Chondrocyte Deformations as a Function of Tibiofemoral Joint Loading Predicted by a Generalized High-Throughput Pipeline of Multi-Scale Simulations

Cells of the musculoskeletal system are known to respond to mechanical loading and chondrocytes within the cartilage are not an exception. However, understanding how joint level loads relate to cell level deformations, e.g. in the cartilage, is not a straightforward task. In this study, a multi-scale analysis pipeline was implemented to post-process the results of a macro-scale finite element (FE) tibiofemoral joint model to provide joint mechanics based displacement boundary conditions to micro-scale cellular FE models of the cartilage, for the purpose of characterizing chondrocyte deformations in relation to tibiofemoral joint loading. It was possible to identify the load distribution within the knee among its tissue structures and ultimately within the cartilage among its extracellular matrix, pericellular environment and resident chondrocytes. Various cellular deformation metrics (aspect ratio change, volumetric strain, cellular effective strain and maximum shear strain) were calculated. To illustrate further utility of this multi-scale modeling pipeline, two micro-scale cartilage constructs were considered: an idealized single cell at the centroid of a 100×100×100 μm block commonly used in past research studies, and an anatomically based (11 cell model of the same volume) representation of the middle zone of tibiofemoral cartilage. In both cases, chondrocytes experienced amplified deformations compared to those at the macro-scale, predicted by simulating one body weight compressive loading on the tibiofemoral joint. In the 11 cell case, all cells experienced less deformation than the single cell case, and also exhibited a larger variance in deformation compared to other cells residing in the same block. The coupling method proved to be highly scalable due to micro-scale model independence that allowed for exploitation of distributed memory computing architecture. The method’s generalized nature also allows for substitution of any macro-scale and/or micro-scale model providing application for other multi-scale continuum mechanics problems

Evaluation of pre-stresses in the menisci of human knee joint using microindentation

To evaluate the pre-stress in the menisci of a human knee joint, the technique of microindentation was adopted. Five specimens each for lateral and medial menisci attached to the tibia were prepared from the knee joints of Korean cadavers to represent the pre-stress state of the meniscus. To create test specimens for the stress-free state of the meniscus, each meniscus was resected from the tibia and cut into three parts, which were subsequently attached to a metal plate. Indentations were carried out in each meniscus in both the pre-stress state and the stress-free state. The pre-stresses in the menisci were evaluated using the load-versus-depth curves. Compressive pre-stresses were found in the menisci. For each indentation region, the pre-stresses in the medial meniscus were higher than in the lateral meniscus. The highest pre-stress in both the lateral and medial meniscus was found in the posterior regions, while the anterior regions experienced the lowest pre-stress. The obtained pre-stresses can be used for the accurate numerical analysis, the fabrication of artificial menisci, and the diagnosis of meniscal disease progression for human knee joints.ope

Effects of degeneration on the compressive and tensile properties of human meniscus

Healthy menisci function within the joint to prevent the underlying articular cartilage from excessive loads. Understanding how mechanical properties of menisci change with degeneration can drive future therapeutic studies to prevent this degeneration. Thus, the goal of this study was to characterize both compressive and tensile moduli of human menisci with varying degrees of gross damage due to osteoarthritis (OA). Twenty four paired menisci were collected from total knee joint replacement patients and the menisci were graded on a scale from 0-4 according to level of gross meniscal degeneration with 0=normal and 4=full tissue maceration. Each meniscus was then sectioned into anterior and posterior regions and subjected to indentation relaxation tests. Samples were sliced into 1. mm thick strips, made into dumbbells using a custom punch, and pulled to failure. Significant decreases in instantaneous compressive modulus were seen in the lateral posterior region between grades 0 and 1 (36% decrease) and in the medial anterior regions between grades 1 and 2 (67% decrease) and 1 and 3 (72% decrease). Changes in equilibrium modulus where seen in the lateral anterior region between grades 1 and 2 (35% decrease), lateral posterior region between grades 0-2 (41% decrease), and medial anterior regions between grades 1 and 2 (59% decrease), 1 and 3 (67% decrease), 2 and 4 (54% decrease), and 3 and 4 (42% decrease). No significant changes were observed in tensile modulus across all regions and degenerative grades. The results of this study demonstrate the compressive moduli are affected even in early stages of gross degeneration, and continue to decrease with increased deterioration. However, osteoarthritic menisci retain a tensile modulus similar to that of previously reported healthy menisci. This study highlights progressive changes in meniscal mechanical compressive integrity as level of gross tissue degradation increases, and thus, early interventions should focus on restoring or preserving compressive integrity

Osseointegration of Prostheses on the Stapes Footplate: Evaluation of the Biomechanical Feasibility by Using a Finite Element Model

Restoration of hearing is one of the main issues of tympanoplasty. Depending on the extent of destruction, the ossicular chain is partially or totally replaced by prostheses. In the unfavorable event of complete ossicular chain destruction with only the stapes footplate remaining in the oval niche, implanting of a columella prosthesis represents the gold standard. Besides ventilation problems, the main causes of unsatisfactory hearing results are dislocation of the prosthesis and poor coupling to the footplate. Therefore, stable fixation of prostheses is desirable but has not been realized to date. In line with our experimental intention to realize a bony prosthesis fixation on the footplate, we designed a finite element model for the simulation of the interacting forces once an osseointegration was achieved. These preliminary results predict the mechanical feasibility of this endeavor and the necessary general preconditions, which have to be carefully considered. A specially designed titanium prosthesis anchor needs a minimal bony fixation of 104 μm accretion height on the footplate to withstand all emerging forces. Therefore, providing a sort of artificial stapedial suprastructure in the form of a firm, preferably bony, integration of a prosthesis anchor on the footplate seems to be realistic and worthwhile from a mechanical and medical point of view