Introduction and Objective. The continued effectiveness of antibiotic loaded bone cements is threatened by antibiotic resistance. The common antiseptic, chlorhexidine (CHX), is a potential alternative to antibiotics in bone cements, but conventional salts are highly soluble, causing burst release and rapid decline to subinhibitory local CHX concentrations. Here, chlorhexidine triphosphate (CHX-TP), a low solubility CHX salt, is investigated as an alternative antimicrobial in PMMA bone cements. The aim was to assess duration of antimicrobial release and antimicrobial efficacy, along with handling, setting and mechanical properties of CHX-TP loaded cements, compared with an existing cement formulation containing gentamicin. Materials and Methods. Palacos R (Heraeus Medical, Newbury, UK) with 0, 1, 4, 7 and 12% CHX-TP (w/w) cements were prepared by combining solid CHX-TP with Palacos R components, and compared with Palacos R+G. All cements were prepared without vacuum and under ISO 5833:2002 conditions. Cements were tested under ISO 5833:2002 for compressive and bending properties, setting time, maximum temperature and doughing time. Antimicrobial release from the cements into deionised water was studied and antimicrobial efficacy of unaged and aged cements against Staphylococcus aureus (ATCC 29213) was assessed using a disc diffusion assay. Results. Compressive strength of CHX-TP loaded cements was not significantly different to Palacos R or Palacos R+G (p > 0.05, all exceeding ISO 5833:2002 minimum of 70 MPa). Mean bending strength was significantly lower with CHX-TP loading (p < 0.05) than bending strength of Palacos R and Palacos R+G, though all bending moduli exceeded the ISO 5833:2002 minimum (1800 MPa). All cements studied were within the ISO 5833:2002 limits for setting time (3 to 15 min), doughing time (≤ 5 min) and maximum temperature (90 . o. C). Mean doughing time for Palacos R, Palacos R+G and Palacos R + 12 % CHX-TP respectively: 52.5 s, 45 s and 45 s. Mean setting time and mean maximum temperature for Palacos R, Palacos R+G and Palacos R + 1, 4, 7 and 12% CHX-TP respectively: 11.00 min (73 . o. C), 11.25 min (72 . o. C), 12.25 min (66 . o. C), 10.50 min (70 . o. C), 10.00 min (70 . o. C), 10.75 min (62 . o. C). Sustained CHX release into deionised water was observed from all Palacos R + CHX-TP cements. Duration varied according to CHX-TP dosing and diminished over time, although to an extent that itself varied with dosing. 1 % CHX-TP ceased releasing CHX at 6.9 weeks; 4 % CHX-TP ceased at 67.7 weeks; 7 % and 12 % CHX-TP were ongoing at 75.5 weeks. Palacos R+G cements ceased releasing detectable levels of gentamicin after 14.4 weeks. Palacos R+G and Palacos R + CHX-TP cement discs showed efficacy against S. aureus (ATCC 29213) when applied as prepared (unaged) to S. aureus bacterial lawns in disc diffusion assays, with CHX-TP cements showing dose dependency. Zone of inhibition (ZOI) size was significantly reduced for Palacos R+G cements and Palacos R + 1% CHX-TP cements after 1 week and 6 weeks aging, compared to ZOI from unaged cements (p < 0.05). ZOI size produced by Palacos R + 4, 7, and 12 % CHX-TP cements did not decline significantly after 6 weeks aging (p > 0.05). Conclusions. CHX-TP can be incorporated into the Palacos R cement matrix up to 12% w/w without deterioration of compressive strength, bending modulus, doughing time, setting time or maximum temperature. Bending strength was significantly reduced at all CHX-TP loadings studied. Palacos R + 4, 7 and 12% CHX-TP cements provided sustained CHX release, exceeding the duration of gentamicin release from Palacos R+G, and showed sustained efficacy against S. Aureus after 6 weeks aging, which was not achieved by Palacos R+G cements

The main problem of infected orthopaedic implants is that the presence of microorganisms in an organized biofilm making them difficult accessible for antibiotics. This biofilm consists of a complex community of microorganisms embedded in an extracellular matrix that forms on surfaces such as an implant. Non-contact induction heating uses pulsed electromagnetic fields to induce so-called ‘eddy currents’ within metal objects which causes them to heat up. This heat causes thermal damage to the bacterial biofilm hence killing the bacteria on the metal implant. The purpose of this study is to determine the effectiveness of induction heating on killing Staphylococcus epidermidis in a biofilm. S. epidermidis biofilms were grown on Titanium alloy (Ti6Al4V) coupons and subsequently were heated with a custom-built induction heater to temperatures of 60°C, 70°C, 80°C and 90°C for 3.5 minutes. Temperature was controlled with an infra-red thermal sensor and micro-controller. We also included two control conditions without induction heating: C1 without induction heating and C2 with chlorhexidine 0.5% in 70% alcohol without induction heating. Experiments were repeated 5 times. In the C1 group (no induction heating), 1.3 * 10(7) colony forming units (CFU)/cm(−2) of S. epidermidis were observed. For 60°C, 70C, 80 C and 90C, a 3.9-log reduction, 5.3-log reduction, 5.5-log reduction and 6.1-log reduction in CFU/cm(−2) were observed, respectively. For the C2 (chlorhexidine) there was a 6.7-log reduction CFU/cm(-2). We concluded that induction heating of Titanium coupons is effective in reducing bacterial load in vitro for S. epidermidis biofilms

Objectives

Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics.

Objectives

To review the current best surgical practice and detail a multi-disciplinary approach that could further reduce joint replacement infection.

Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair.

Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed.

Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections.

Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors.

The aim of this study was to determine the effectiveness of antibiotic-impregnated implants in the prevention of bone infection. We used a model of contaminated fracture in goats to evaluate four treatment groups: no treatment, hand-made tobramycin-impregnated polymethylmethacrylate beads, commercially-available tobramycin-impregnated calcium sulphate pellets and commercially-available tobramycin-impregnated polymethylmethacrylate beads. Three weeks after intraosseous inoculation with streptomycin-resistant Staphylococcus aureus tissue cultures showed no evidence of infection in any of the antibiotic-treated groups. All of the cultures were positive in the untreated group. These results show that effective local antibiotic delivery can be obtained with both commercially-available products and with hand-made polymethylmethacrylate beads. The calcium sulphate pellets have the advantage of being bioabsorbable, thereby obviating the need for a second procedure to remove them.

We have examined the deterioration of implant fixation after withdrawal of parathyroid hormone (PTH) in rats. First, the pull-out force for stainless-steel screws in the proximal tibia was measured at different times after withdrawal. The stimulatory effect of PTH on fixation was lost after 16 days. We then studied whether bisphosphonates could block this withdrawal effect. Mechanical and histomorphometric measurements were conducted for five weeks after implantation. Subcutaneous injections were given daily. Specimens treated with either PTH or saline during the first two weeks showed no difference in the mechanical or histological results (pull-out force 76 N vs 81 N; bone volume density 19% vs 20%). Treatment with PTH for two weeks followed by pamidronate almost doubled the pull-out force (152 N; p < 0.001) and the bone volume density (37%; ANOVA, p < 0.001). Pamidronate alone did not have this effect (89 N and 25%, respectively). Thus, the deterioration can be blocked by bisphosphonates. The clinical implications are discussed.

We have studied the effects of bupivacaine on human and bovine articular chondrocytes in vitro. Time-lapse confocal microscopy of human articular chondrocytes showed > 95% cellular death after exposure to 0.5% bupivacaine for 30 minutes. Human and bovine chondrocytes exposed to 0.25% bupivacaine had a time-dependent reduction in viability, with longer exposure times resulting in higher cytotoxicity. Cellular death continued even after removal of 0.25% bupivacaine. After exposure to 0.25% bupivacaine for 15 minutes, flow cytometry showed bovine chondrocyte viability to be 41% of saline control after seven days. After exposure to 0.125% bupivacaine for up to 60 minutes, the viability of both bovine and human chondrocytes was similar to that of control groups.

These data show that prolonged exposure 0.5% and 0.25% bupivacaine solutions are potentially chondrotoxic.