The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats.

Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group.

Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function.

We reviewed the clinical and radiological results of 131 patients who underwent acetabular revision for aseptic loosening with impacted bone allograft and a cemented acetabular component. The mean follow-up was 51.7 months (24 to 156).

The mean post-operative Merle D’Aubigné and Postel scores were 5.7 points (4 to 6) for pain, 5.2 (3 to 6) for gait and 4.5 (2 to 6) for mobility. Radiological evaluation revealed migration greater than 5 mm in four acetabular components. Radiological failure matched clinical failure. Asymptomatic radiolucent lines were observed in 31 of 426 areas assessed (7%). Further revision was required in six patients (4.5%), this was due to infection in three and mechanical failure in three. The survival rate for the reconstruction was 95.8% (95% confidence interval 92.3 to 99.1) overall, and 98%, excluding revision due to sepsis.

Our study, from an independent centre, has reproduced the results of the originators of the method.

Post-traumatic arthritis is a frequent consequence of articular fracture. The mechanisms leading to its development after such injuries have not been clearly delineated. A potential contributing factor is decreased viability of the articular chondrocytes. The object of this study was to characterise the regional variation in the viability of chondrocytes following joint trauma. A total of 29 osteochondral fragments from traumatic injuries to joints that could not be used in articular reconstruction were analysed for cell viability using the fluorescence live/dead assay and for apoptosis employing the TUNEL assay, and compared with cadaver control fragments.

Chondrocyte death and apoptosis were significantly greater along the edge of the fracture and in the superficial zone of the osteochondral fragments. The middle and deep zones demonstrated significantly higher viability of the chondrocytes. These findings indicate the presence of both necrotic and apoptotic chondrocytes after joint injury and may provide further insight into the role of chondrocyte death in post-traumatic arthritis.

This prospective study evaluates the role of new laboratory markers in the diagnosis of deep implant infection in 78 patients (41 men and 37 women) with a revision total knee or hip replacement.

The mean age at the time of operation was 64.0 years (19 to 90). Intra-operative cultures showed that 21 patients had a septic and 57 an aseptic total joint replacement. The white blood cell count, the erythrocyte sedimentation rate and levels of C-reactive protein, interleukin-6, procalcitonin and tumour necrosis factor (TNF)-α were measured in blood samples before operation. The diagnostic cut-off values were determined by Received Operating Characteristic curve analysis.

C-reactive protein (> 3.2 md/dl) and interleukin-6 (> 12 pg/ml) have the highest sensitivity (0.95). Interleukin-6 is less specific than C-reactive protein (0.87 vs 0.96). Combining C-reactive protein and interleukin-6 identifies all patients with deep infection of the implant. Procalcitonin (> 0.3 ng/ml) and TNF-α (> 40 ng/ml) are very specific (0.98 vs 0.94) but have a low sensitivity (0.33 vs 0.43).

The combination of C-reactive protein and interleukin-6 measurement provide excellent screening tests for infection of a deep implant. A highly specific marker such as procalcitonin and pre-operative aspiration of the joint might be useful in identifying patients with true positive C-reactive protein and/or interleukin-6 levels.

The recent resurgence in the use of metal-on-metal bearings has led to fresh concerns over metal wear and elevated systemic levels of metal ions.

In order to establish if bearing diameter influences the release of metal ions, we compared the whole blood levels of cobalt and chromium (at one year) and the urinary cobalt and chromium output (at one to three and four to six years) following either a 50 mm or 54 mm Birmingham hip resurfacing or a 28 mm Metasul total hip replacement. The whole blood concentrations and daily output of cobalt and chromium in these time periods for both bearings were in the same range and without significant difference.

Critical size defects in ovine tibiae, stabilised with intramedullary interlocking nails, were used to assess whether the addition of carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant would affect the implant’s efficacy for bone regeneration. The biomaterial carriers were a ‘putty’ carrier of carboxymethylcellulose and bovine-derived type-I collagen (OPP) or the standard with collagen alone (OPC). These two treatments were also compared to “ungrafted” negative controls. Efficacy of regeneration was determined using radiological, biomechanical and histological evaluations after four months of healing. The defects, filled with OPP and OPC, demonstrated radiodense material spanning the defect after one month of healing, with radiographic evidence of recorticalisation and remodelling by two months. The OPP and OPC treatment groups had equivalent structural and material properties that were significantly greater than those in the ungrafted controls. The structural properties of the OPP- and OPC-treated limbs were equivalent to those of the contralateral untreated limb (p > 0.05), yet material properties were inferior (p < 0.05). Histopathology revealed no residual inflammatory response to the biomaterial carriers or OP-1. The OPP- and OPC-treated animals had 60% to 85% lamellar bone within the defect, and less than 25% of the regenerate was composed of fibrous tissue. The defects in the untreated control animals contained less than 40% lamellar bone and more than 60% was fibrous tissue, creating full cortical thickness defects. In our studies carboxymethylcellulose did not adversely affect the capacity of the standard OP-1 implant for regenerating bone.

We reviewed 142 consecutive primary total hip replacements implanted into 123 patients between 1988 and 1993 using the Exeter Universal femoral stem. A total of 74 patients (88 hips) had survived for ten years or more and were reviewed at a mean of 12.7 years (10 to 17). There was no loss to follow-up.

The rate of revision of the femoral component for aseptic loosening and osteolysis was 1.1% (1 stem), that for revision for any cause was 2.2% (2 stems), and for re-operation for any cause was 21.6% (19 hips). Re-operation was because of failure of the acetabular component in all but two hips.

All but one femoral component subsided within the cement mantle to a mean of 1.52 mm (0 to 8.3) at the final follow-up. One further stem had subsided excessively (8 mm) and had lucent lines at the cement-stem and cement-bone interfaces. This was classified as a radiological failure and is awaiting revision. One stem was revised for deep infection and one for excessive peri-articular osteolysis. Defects of the cement mantle (Barrack grade C and D) were found in 28% of stems (25 hips), associated with increased subsidence (p = 0.01), but were not associated with endosteal lysis or failure.

Peri-articular osteolysis was significantly related to the degree of polyethylene wear (p < 0.001), which was in turn associated with a younger age (p = 0.01) and male gender (p < 0.001).

The use of the Exeter metal-backed acetabular component was a notable failure with 12 of 32 hips (37.5%) revised for loosening. The Harris-Galante components failed with excessive wear, osteolysis and dislocation with 15% revised (5 of 33 hips). Only one of 23 hips with a cemented Elite component (4%) was revised for loosening and osteolysis.

Our findings show that the Exeter Universal stem implanted outside the originating centre has excellent medium-term results.

We have investigated the role of the penetration of saline on the shear strength of the cement-stem interface for stems inserted at room temperature and those preheated to 37°C using a variety of commercial bone cements. Immersion in saline for two weeks at 37°C reduced interfacial strength by 56% to 88% after insertion at room temperature and by 28% to 49% after preheating of the stem. The reduction in porosity as a result of preheating ranged from 71% to 100%. Increased porosity correlated with a reduction in shear strength after immersion in saline (r = 0.839, p < 0.01) indicating that interfacial porosity may act as a fluid conduit.

Peri-prosthetic bone loss caused by stress shielding may be associated with aseptic loosening of femoral components. In order to increase primary stability and to reduce stress shielding, a three-dimensional, cementless individual femoral (Evolution K) component was manufactured using pre-operative CT scans. Using dual energy x-ray absorptiometry, peri-prosthetic bone density was measured in 43 patients, three months, six months, 3.6 and 4.6 years after surgery. At final follow-up there was a significant reduction in mean bone density in the proximal Gruen zones of −30.3% (zone 7) and −22.8% (zone 1). The density in the other zones declined by a mean of between −4% and −16%. We conclude that the manufacture of a three-dimensional, custom-made femoral component could not prevent a reduction in peri-prosthetic bone density.

We carried out a clinical and radiological review of 103 cementless primary hip arthroplasties with a tapered rectangular grit-blasted titanium press-fit femoral component and a threaded conical titanium acetabular component at a mean follow-up of 14.4 years (10.2 to 17.1).

The mean Harris hip score at the last follow-up was 89.2 (32 to 100). No early loosening and no fracture of the implant were found. One patient needed revision surgery because of a late deep infection. In 11 hips (10.7%), the reason for revision was progressive wear of the polyethylene liner. Exchange of the acetabular component because of aseptic loosening without detectable liner wear was carried out in three hips (2.9%).

After 15 years the survivorship with aseptic loosening as the definition for failure was 95.6% for the acetabular component and 100% for the femoral component.

Metal-on-metal hip bearings are being implanted into younger patients. The consequence of elevated levels of potentially carcinogenic metal ions is therefore a cause for concern. We have determined the levels of cobalt (Co), chromium (Cr), titanium (Ti) and vanadium (Va) in the urine and whole blood of patients who had had metal-on-metal and metal-on-polyethylene articulations in situ for more than 30 years. We compared these with each other and with the levels for a control group of subjects.

We found significantly elevated levels of whole blood Ti, Va and urinary Cr in all arthroplasty groups. The whole blood and urine levels of Co were grossly elevated, by a factor of 50 and 300 times respectively in patients with loose metal-on-metal articulations when compared with the control group. Stable metal-on-metal articulations showed much lower levels. Elevated levels of whole blood or urinary Co may be useful in identifying metal-on-metal articulations which are loose.

We compared the five- to seven-year clinical and radiological results of the metal-on-metal Birmingham hip resurfacing with a hybrid total hip arthroplasty in two groups of 54 hips, matched for gender, age, body mass index and activity level.

Function was excellent in both groups, as measured by the Oxford hip score, but the Birmingham hip resurfacings had higher University of California at Los Angeles activity scores and better EuroQol quality of life scores. The total hip arthroplasties had a revision or intention-to-revise rate of 8%, and the Birmingham hip resurfacings of 6%. Both groups demonstrated impending failure on surrogate end-points. Of the total hip arthroplasties, 12% had polyethylene wear and osteolysis under observation, and 8% of Birmingham hip resurfacings showed migration of the femoral component. Polyethylene wear was present in 48% of the hybrid hips without osteolysis. Of the femoral components in the Birmingham hip resurfacing group which had not migrated, 66% had radiological changes of unknown significance.

Bovine and human articular chondrocytes were seeded in 2% alginate constructs and cultured for up to 19 days in a rotating-wall-vessel (RWV) and under static conditions. Culture within the RWV enhanced DNA levels for bovine chondrocyte-seeded constructs when compared with static conditions but did not produce enhancement for human cells. There was a significant enhancement of glycosaminoglycans and hydroxyproline synthesis for both bovine and human chondrocytes. In all cases, histological analysis revealed enhanced Safranin-O staining in the peripheral regions of the constructs compared with the central region. There was an overall increase in staining intensity after culture within the RWV compared with static conditions. Type-II collagen was produced by both bovine and human chondrocytes in the peripheral and central regions of the constructs and the staining intensity was enhanced by culture within the RWV. A capsule of flattened cells containing type-I collagen developed around the constructs maintained under static conditions when seeded with either bovine or human chondrocytes, but not when cultured within the RWV bioreactor.

Clinical experience of impaction bone grafting for revision knee arthroplasty is limited, with initial stability of the tibial tray emerging as a major concern. The length of the stem and its diameter have been altered to improve stability. Our aim was to investigate the effect of the type of stem, support of the rim and graft impaction on early stability of the tray.

We developed a system for impaction grafting of trays which we used with morsellised bone in artificial tibiae. Trays with short, long thick or long thin stems were implanted, with or without support of the rim. They were cyclically loaded while measuring relative movement.

Long-stemmed trays migrated 4.5 times less than short-stemmed trays, regardless of diameter. Those with support migrated 2.8 times less than those without. The migration of short-stemmed trays correlated inversely with the density of the impacted groups. That of impaction-grafted tibial trays was in the range reported for uncemented primary trays. Movements of short-stemmed trays without cortical support were largest and sensitive to the degree of compaction of the graft. If support of the rim was sufficient or a long stem was used, impacted morsellised bone graft achieved adequate initial stability.

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model.

A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 × 10⁷ AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 10⁷ naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated.

Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months.

Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model.

The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.