Tungsten has been increasing in demand for use in manufacturing and recently, medical devices, as it imparts flexibility, strength, and conductance of metal alloys. Given the surge in tungsten use, our population may be subjected to elevated exposures. For instance, embolism coils made of tungsten have been shown to degrade in some patients. In a cohort of breast cancer patients who received tungsten-based shielding for intraoperative radiotherapy, urinary tungsten levels remained over tenfold higher 20 months post-surgery. In vivo models have demonstrated that tungsten exposure increases tumor metastasis and enhances the adipogenesis of bone marrow-derived mesenchymal stem cells while inhibiting osteogenesis. We recently determined that when mice are exposed to tungsten [15 ppm] in their drinking water, it bioaccumulates in the intervertebral disc tissue and vertebrae. This study was performed to determine the toxicity of tungsten on intervertebral disc.

Bovine nucleus pulposus (bNP) and annulus fibrosus (bAF) cells were isolated from bovine caudal tails. Cells were expanded in flasks then prepared for 3D culturing in alginate beads at a density of 1×10^∧6 cells/mL. Beads were cultured in medium supplemented with increasing tungsten concentrations in the form of sodium tungstate [0, 0.5, 5, 15 ug/mL] for 12 days. A modified GAG assay was performed on the beads to determine proteoglycan content and Western blotting for type II collagen (Col II) synthesis. Cell viability was determined by counting live and dead cells in the beads following incubation with the Live/Dead Viability Assay kit (Thermo Fisher Scientific). Cell numbers in beads at the end of the incubation period was determined using Quant-iT dsDNA Assay Kit (Thermo Fisher Scientific)

Tungsten dose-dependently decreased the synthesis of proteoglycan in IVD cells, however, the effect was significant at the highest dose of 15 ug/mL. (n=3). Furthermore, although tungsten decreased the synthesis of Col II in IVD cells, it significantly increased the synthesis of Col I. Upregulation of catabolic enzymes ADAMTS4 and −5 were also observed in IVD cells treated with tungsten (n=3). Upon histological examination of spines from mice treated with tungsten [15 ug/mL] in their drinking water for 30 days, disc heights were diminished and Col I upregulation was observed (n=4). Cell viability was not markedly affected by tungsten in both bNP and bAF cells, but proliferation of bNP cells decreased at higher concentration. Surprisingly, histological examination of IVDs and gene expression analysis demonstrated upregulation of NGF expression in both NP and AF cells. In addition, endplate capillaries showed increases in CGRP and PGP9.5 expression as determined on histological sections of mouse IVDs, suggesting the development of sensory neuron invasion of the disc.

We provide evidence that prolonged tungsten exposure can induce disc fibrosis and increase the expression of markers associated with pain. Tungsten toxicity may play a role in disc degeneration disease.

INTRODUCTION

Mechanical overloading of the knee can occur during activities of daily living such as stair climbing, jogging, etc. In this finite element study we aim to investigate which parameters could detrimentally influence peri-implant bone in the tibial reconstructed knee. Bone quality and patient variables are potential factors influencing knee overloading (Zimmerman 2016).

This study documents the gross and histologic structure of the infrapatellar plica, and fat pad, and adds to an earlier report to the COA. The important new findings are that the femoral attachment of the plica is an enthesis, and that the plica itself is.

This study seeks to demonstrate that the structure of the fat pad (FP) and infrapatellar plica (IPP) is that of an enthesis organ.

Twelve fresh frozen cadaver knees, each with an IPP, were dissected and the gross anatomic features recorded. The IPP and FP were harvested for study. Representative histologic sections were prepared on tissue fixed in 10% neutral buffered formalin, embedded in paraffin, cut at 4 microns on a rotatory microtome. Staining techniques included hematoxylin and eosin, Masson's trichrome, elastic stain and S100. Appropriate decalcification of sections of the femoral insertion of the IPP was performed. All sections were examined by light microscopy at low, medium and high power. IPP types included 8 separate, 1 split, 2 fenestrated, and one vertical septum. The origin of the IPP is a fibrous arc arising from the apex of the notch separate from the margin of the articular cartilage. This attachment site is the instant centreof rotation of the IPP and FP; they are thus not isometric. The central zone of the IPP consists of a mix of connective tissue types.

Representative sections taken of the femoral attachment of the IPP display a transition zone between dense fibrillar collagen of the IPP, then fibrocartilage and cortical bone similar to a ligament attachment site or enthesis. The central plica histology is composed predominantly of dense regular connective tissue with variable clear space between the collagen bundles, and is thus ligamentous. There is abundant elastase staining throughout, as well as crimping of the collagen suggesting capacity for stretch. S100 staining demonstrates nerves around and in the substance of the IPP. The central body shows lobulated collections of mature adipose tissue admixed with loose connective tissue, containing abundant small peripheral nerves and vessels (all showing crimping and redundancy), merging with the dense fibrous tissue of the IPP. The FP is highly innervated, deformable, and fibro-fatty. Its histology shows lobules of fat, separated by connective tissue septa, which merge with the synovial areolar membrane surrounding the FP.

The linked structures, IPP, central body, and FP occupy the anterior compartment, and function as an enthesis organ: the IPP tethers the FP via the central body and together they rotate around the femoral origin of the IPP. They are not isometric, and must stretch and relax with knee motion. The histology correlates with this requirement. The origin of the IPP is an enthesis, a new observation. Elastase staining, redundancy of vessels and nerves, crimping and redundancy of the dense connective tissue all reflect the requirement to deform. The fat pad merges with the central body, both highly innervated space fillers, tethered by the IPP, which is a non-isometric ligament, also containing nerves. The important clinical significance of these structures is that release of the IPP at the origin reuces or eliminates anterior knee pain in most.

INTRODUCTION:

Clinical densitometry studies indicate that following TKR implantation there is loss of bone mineral density in regions around the implant. Bone density below the tibial tray has been reported to decrease 36% at eight years after TKR. This bone loss (∼5%/year) is substantially greater than osteoporosis patients in the same age group (∼1–2%/year) and could contribute the loss of mechanical support provided by the peri-implant leading to loosening of components in the long term. High patient mass and body mass index have also been implicated in increased loosening rates, and was thought to be due to high stress or strain on the tibial constructs. These findings suggest that peri-implant bone strain may be affected by time in service and patient factors such as body mass.

The goal of this project was to assess the proximal tibial bone strain with biomechanical loading using en bloc retrieved TKR tibial components. Note that the implants were not obtained from revision surgery for a loose implant, but rather after death; thus the implants can be considered to be successful for the lifetime of the patient. We asked two research questions, guided by the clinical and laboratory observations: (1) are the peri-implant bone strain magnitudes for cemented tibial components greater for implants with more time in service and from older donors?, (2) is tibial bone strain greater for constructs from donors with high body weight and lower peri-implant BMD?

INTRODUCTION:

Aseptic loosening continues to be a short and long-term complication for patients with cemented knee replacements. Changes in cemented total knee replacement (TKR) fixation have been limited to assessment of radiographic changes at the implant-bone interface and quantification of component migration. The goal of this study was to determine the interlock morphology between cement and trabecular bone using en bloc postmortem retrieved TKR. Note that these retrievals were not obtained from revision surgery for a loose implant, but rather after death. Thus the implants can be considered successful for the lifetime of the patient. We hypothesized that constructs with greater time in service have less interlock between cement and bone and constructs with more estimated initial interlock sustain more interlock with in-vivo service.

In cemented total hip arthroplasty, the cement-bone interface can be considerably degraded in less than one year in-vivo service (Figure 1). This makes the interface much weaker relative to the direct post-operative situation. Retrieval studies show that patients do, to a certain extent, not suffer from the degraded cement-bone interface itself. It is, however, unknown whether the degraded cement-bone interface affects other failure mechanisms in the cemented hip reconstruction. A good understanding of the mechanics of the cement-bone interface is therefore essential. The aim of this study was to investigate the mechanics of the cement-bone interface in the direct post-operative and degraded situation by the utilization of finite element analysis (FEA) and laboratory experiments. It was subsequently analyzed how the mechanics of the cement-bone interface affect failure of the cement mantle in terms of crack formation.

In order to investigate the mechanical response of the cement-bone interface, laboratory prepared (direct post-operative state) and postmortem (degraded state) specimens were loaded in various directions in the laboratory and FEA environment. From all specimens, multiple interface morphology parameters were documented, which were related to the interfacial response and subsequently converted to a numerical cohesive model. As a validation, this cohesive model was implemented into two FEA models of transverse sections of cemented hip reconstructions with distinct mechanical characteristics (Figure 2). Finally, the differences in fatigue crack formation in a complete hip reconstruction were determined by varying the cement-bone interface compliance (Figure 3).

When loaded in multiple directions, the interface compliance could not be related to the cement interdigitation depth (r²=0.08). However, compliance did correlate to the gap thickness between the bone and cement (r²=0.81) and the amount of interfacial contact (r²=0.50). Surprisingly, for the same amount of contact, the interface was more compliant in degraded state than in the direct post-operative state. The mechanical response of the experimental and FEA cement-bone interface tests could, independent on the direct post-operative or degraded state, successfully be described by a cohesive model. The cohesive model was even more confirmed by the successful reproduction of the mechanics of the retrieved transverse sections. When the cohesive model was implemented in a complete reconstruction, we found that a compliant cement-bone interface resulted in considerably more fatigue cracks in the cement mantle than a very stiff interface.

This study showed that an increased compliancy of the cement-bone interface results in an increase of cement cracks in the cement mantle. It is therefore crucial to minimize the interfacial gaps and, as a result, increase the amount of contact between the bone and cement to generate a stiff cement-bone interface. It is, unfortunately, unknown how this well fixed interface can be maintained. We finally conclude that the derived cohesive model of the cement-bone interface can be used for multiple applications in orthopaedics, including pre-clinical of implants and patient specific studies of failed cemented reconstructions.