Identification of novel therapeutics to accelerate acute fracture healing remains critical. A prostaglandin EP-2 receptor agonist (CP-533,536) has demonstrated acceleration of fracture healing in preclinical models. The objective of this study is to assess the efficacy of a single dose of CP-533,536 in subjects with a closed fracture of the tibial shaft using radiographic measurements compared to placebo treatment. In a phase II randomised, blinded, placebo-controlled trial, the efficacy of a single local injection of three doses of CP-533,536 (0.5mg, 1.5mg and 15mg) was compared to a placebo and a standard of care arm in patients with closed tibial shaft fractures. The tibial fractures were treated with reamed inter-locked intramedullary nails. Patients were followed at two week intervals to six months with a final evaluation at one year. Fracture healing was independently adjudicated by a radiologist panel and an orthopaedic surgeon panel.Background
Methods
Problems associated with soft tissues of the stump and attachment of prosthetic devices for amputees remains a considerable problem. These problems are associated with the transmission of load through the soft tissues of the stump and difficulty in attaching the prosthetic device. Several devices have an osteointegrated transcutaneous prosthesis attached to the residual bone onto which an exo-prostheses is secured thereby transmitting load directly through the skeleton. Infection of these devices is a key issue. A biomimetic intraosseous transcutaneous device for amputees known as ITAP has been developed which is based on deer antler morphology. We have shown that in deer antlers the dermal and epithelial tissues are tethered by collagen fibres which originate from pores in the bone. In a caprine model where the soft tissue interface of ITAP is porous, dermal and epithelial integration occurs creating a seal and preventing infection. In two clinical veterinary cases an ITAP implant has been successfully used in trans-radial canine amputees. A human trans-humeral amputee who previously could not wear their exo-prosthesis has been treated with ITAP. The surgery was single stage procedure and involved the insertion of an uncemented intramedullary stem into the residual humerus. A porous flange structure positioned adjacent to the dermal tissue which had most of the hypodermis removed was used to promote soft tissue ingrowth. At two years' post-operation the skin seal has been maintained, there has been no incidence of infection, the patient wears their exo-prostheses for over 8 hours a day and has an almost complete range of shoulder motion. The use of ITAP device in selected cases may revolutionise the way amputees are surgically treated, lead to increased activity levels and more normal life styles in these patients.
Autologous chondrocyte implantation (ACI) and mosaicplasty (MP) are two methods of repair of symptomatic articular cartilage defects in the adult knee. This study represents the only long-term comparative clinical trial of the two methods. A prospective, randomised comparison of the two modalities involving 100 patients with symptomatic articular cartilage lesions was undertaken. Patients were followed for ten years. Pain and function were assessed using the modified Cincinnati score, Bentley Stanmore Functional rating system and visual analogue scores. ‘Failure’ was determined by pain, a poor outcome score and arthroscopic evidence of graft disintegration.Background
Methods
Autologous chondrocyte implantation is now a recognised treatment for patients with knee pain secondary to articular cartilage defects. The initial technique involving periosteum as the cover for the implanted cells (ACI-P) has been modified to the use of a type I/III collagen membrane (ACI-C). Matrix-induced Autologous Chondrocyte Implantation (MACI) is a technique in which autologous donor chondrocytes are implanted onto the collagen membrane and then fixed into the defect with fibrin glue. We performed a prospective randomised comparison of 247 patients (126 ACI and 121 MACI). Patients' pain and function were assessed with mean follow-up of 42 months. Function was measured using the Modified Cincinnati and Stanmore Scoring systems. Arthroscopic assessment was by the ICRS classification. The influence of the size and site of the lesion, sex, age and previous knee surgery on the results was analysed. The Modified Cincinnati score showed a mean 17.5 point rise from pre-operative scores in the ACI group and 19.6 point rise in the MACI group. Pain, measured using the Visual Analogue Score, showed an improvement in both arms of the trial. Both chondrocyte implantation methods showed improvement in 86% of patients clinically and arthroscopically, with excellent and good results in 50% and fair results in 30% of patients. 20% of patients showed no improvement in function but none were worse. There were no serious complications. Limited histological analysis showed hyaline cartilage in a higher but non-significant proportion of ACI-C cases. With over 11 years' experience in the use of both forms of cartilage implantation we have established more precisely the indications for chondrocyte implantation. Although MACI is technically a more attractive option in most cases, because of ease and speed of the procedure, longer term follow-up is required to assess the longevity of ACI-C and MACI and the effect on prevention of ‘early-onset’ Osteoarthritis.
Orthopaedic cobalt chromium particles and ions can induce indirect DNA damage and chromosome aberrations in human cells on the other side of a cellular barrier in tissue culture. This occurs by intercellular signalling across the barrier. We now show that the threshold for this effect depends on the metal form and the particle composition. Ionic cobalt and chromium induced single strand breaks at concentrations equivalent to those found in the blood of patients with well functioning metal on metal hip prostheses. However, they only caused double strand breaks if the chromium was present as chromium (VI), and did not induce chromosome aberrations. Nanoparticles of cobalt chromium alloy caused DNA double strand breaks and chromosome aberrations, of which the majority were tetraploidy. Ceramic nanoparticles induced only single strand breaks and/or alkaline labile sites when indirectly exposed to human fibroblasts. The assessment of reproductive risk from maternal exposure to biomaterials, especially those liberated by orthopaedic implants, is not yet possible with epidemiology. Whilst the barrier model used here differs from the in vivo situation in several respects, it may be useful as a framework to evaluate biomaterial induced damage across physiological barriers.
The articulating surfaces of a new metal-on-metal (MoM) hip prosthesis system were modified with the ceramic Titanium-Niobium-Nitride (TiNbN) by Physical Vapor Deposition (PVD). The purpose of the study was to investigate whether the elevation of the ion levels of chromium and cobalt, normally seen in the blood of patients after MoM hip arthroplasty, can be prevented by ceramic engineering of the articulating metal surfaces. the ACCIS components (manufactured by Implantcast GmbH, Buxtehude, Germany from casted hi-carbon Co-Cr-Mo alloy) are heat treated, polished and micro-surface finished. Then TiNbN ceramic is integrated into the metal surfaces by PVD. 200 ACCIS resurfacing hip prostheses were implanted in three centres: Morriston Hospital, Swansea and Neville Hall Hospital, Abergavenny in the UK and Arthro Clinic, Hamburg, Germany. Blood samples of 60 randomly selected patients were analysed before surgery and at intervals of 3, 6, 12 and 24 months after surgery. Independent trace metal measurements were performed at the Universitätsklinikum Carl Gustav Carus Dresden, Germany.Introduction
Materials and methods
