Orthopaedic

This study investigated the concept of using plates to attach endoprostheses to bone after segmental resection for bone tumours in an animal model. Titanium alloy plates integrated with the prosthesis and coated with hydroxyapatite were attached to bone by screws. This type of uncemented fixation relied on the induction of periosteal bone formation into and around the plates to secure the implant to bone. Tow, three, and six-slotted plate designs were investigated. On retrieval, each plate was securely fixed by new bone. Bone apposition on the external surface of the plates occurred through a combination of periosteal bone production, invasion of bone through slots in the plate, and bone growth over the ends of the plates. Most plates became incorporated into a remodelled cortex. Higher bone turnover rates (μm day−1) were seen in bone in the slots of the plate compared with normal cortical bone turnover (p < 0.05). Significantly higher rates of turnover were measured beneath slotted parts of the plates compared with regions below the unslotted parts (p < 0.05). The cross-sectional area of bone surrounding the six-plate implant design was significantly higher than that of the three-plate (p < 0.05) and two-plate (p < 0.05) designs. In addition, significantly more bone formed adjacent to the six-plated implant design compared with that in the contralateral limb (p = 0.002). However, no significant difference was found when the total cortical area around the three-plated design was compared with that of the contralateral limb (p = 0.63). In contrast, significantly less bone was measured adjacent to the two-plate design than in the untreated limb (p = 0.001). Image analysis also demonstrated increased cortical porosity adjacent to the six-plate design compared with the three-plate (p = 0.004) and two-plate (p < 0.05) designs. Finite element analysis demonstrated that the six and three-plate designs increased the second moment of area compared with that in the left tibia (p = 0.003 and 0.066, respectively). However, the attachment of the more flexible two-plate design did not significantly increase the second moment of area compared with that in the contralateral limb (p = 0.235). It was concluded that due to both mechanical and biological effects, the hydroxyapatite-coated plate designs generated new bone that enhanced fixation and encouraged plate integration into the load-bearing structure of the cortex. This method of fixation may be an alternative to the use of intramedullary cemented stems in patients requiring bone tumour implants and may be the only way to preserve the joint in difficult cases where only short segments of bone remain.

Osteolysis induced by ultra high molecular weight polyethylene wear debris is one of the primary factors limiting the lifespan of total hip replacements. Crosslinking polyethylene is known to improve its wear resistance in certain industrial applications, and crosslinked polyethylene acetabular cups have shown improved wear resistance in two clinical studies. In the present study, crosslinked polyethylene cups were produced by two methods. Chemically crosslinked cups were produced by mixing a peroxide with ultra high molecular weight polyethylene powder and then molding the cups directly to shape. Radiation-crosslinked cups were produced by exposing conventional extruded ultra high molecular weight polyethylene bar stock to gamma radiation at various doses from 3.3 to 100 Mrad (1 Mrad = 10 kGy), remelting the bars to extinguish residual free radicals (i.e., to minimize long-term oxidation), and then machining the cups by conventional techniques. In hip-joint simulator tests lasting as long as 5 million cycles, both types of crosslinked cups exhibited dramatically improved resistance to wear. Artificial aging of the cups by heating for 30 days in air at 80°C induced oxidation of the chemically crosslinked cups. However, a chemically crosslinked cup that was aged 2.7 years at room temperature had very little oxidation. Thus, whether substantial oxidation of chemically crosslinked polyethylene would occur at body temperature remains unclear. The radiationcrosslinked remelted cups exhibited excellent resistance to oxidation. Because crosslinking can reduce the ultimate tensile strength, fatigue strength, and elongation to failure of ultra high molecular weight polyethylene, the optimal crosslinking dose provides a balance between these physical properties and the wear resistance of the implant and might substantially reduce the incidence of wear-induced osteolysis with total hip replacements.

More than 1,300 Austin Moore hemiarthroplasties have been reviewed in the literature, with no reports of fracture of the stem. Many patients with these hip implants had good function. The lack of stem fractures in patients with good function has not been explained and contrasts with stem fractures that have occurred in patients with cemented prostheses of other designs during the same time. We used three-dimensional finite-element analysis and free-body diagrams to explain the lack of fractures for this device by a description of the probable load-transfer mechanisms between the prosthesis and the bone. Results from our finite-element analysis indicate that, with good calcar-collar support, the stresses in the stem are small because the stem portion of the prosthesis and the bone are uncoupled and, consequently, do not share the resultant bending moment of the head and abductor forces. If the stem is coupled to the bone so that the resultant bending moment is shared, high stresses in the stem are predicted; such stresses are inconsistent with the complete absence of fractures of these prostheses. The results of the finite-element analysis further showed that loss of calcar-collar support with proximal fixation through the fenestrations resulted in high stresses in the stem and stress shielding of the proximal medial cortex. The uncoupled prosthesis also may be modeled with a free-body diagram as a three-force member loaded at the head, stem tip, and in the proximal region. With this model, it can be shown that the reaction force of the stem tip, and thus the peak bending stress in the stem, increases as calcar-collar support is decreased. If there is no calcar-collar support, proximal support must be provided by some combination of integration of bone in the fenestrations and wedging due to the lateral-medial taper of the device. Stresses in the stem are largest when there is no wedging, but high stresses develop in the cancellous bone in the fenestrations. When there is wedging, stresses in the stem can be low, but stresses in the supporting cancellous bone can be high; additional proximal support through the fenestrations substantially reduces these bone stresses. If reduced stresses in the cancellous bone are indicative of a stable device, these mechanisms indicate that fractures of the Austin Moore prosthesis have not occurred in normally loaded hips because load was transferred primarily either through the collar or by wedging, with additional support at the fenestrations.

Thrombospondin (TSP) signals focal adhesion disassembly (the intermediate adhesive state) through interactions with cell surface calreticulin (CRT). TSP or a peptide (hep I) of the active site induces focal adhesion disassembly through binding to CRT, which activates phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinase (ERK) through Galphai2 proteins. Because CRT is not a transmembrane protein, it is likely that CRT signals as part of a coreceptor complex. We now show that low density lipoprotein receptor-related protein (LRP) mediates focal adhesion disassembly initiated by TSP binding to CRT. LRP antagonists (antibodies, receptor-associated protein) block hep I/TSP-induced focal adhesion disassembly. LRP is necessary for TSP/hep I signaling because TSP/hep I is unable to stimulate focal adhesion disassembly or ERK or PI3K signaling in fibroblasts deficient in LRP. LRP is important in TSP-CRT signaling, as shown by the ability of hep I to stimulate association o...