The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries.

This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors.

We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged < 65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders.

Laboratory-defined T-cell lymphopenia was present in13 patients (15%) (CD8⁺ lymphopenia) and 11 patients (13%) (CD3⁺ lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8⁺ lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets.

The role of modular tibial implants in total knee replacement is not fully defined. We performed a prospective randomised controlled clinical trial using radiostereophotogrammetric analysis to compare the performance of an all-polyethylene tibia with a metal-backed cruciate-retaining condylar design, PFC-∑ total knee replacement for up to 24 months. There were 51 patients who were randomised into two treatment groups. There were 10 subsequent withdrawals, leaving 21 all-polyethylene and 20 metal-backed tibial implants. No patient was lost to follow-up. There were no significant demographic differences between the groups. At two years one metal-backed implant showed migration > 1 mm, but no polyethylene implant reached this level. There was a significant increase in the SF-12 and Oxford knee scores after operation in both groups.

In an uncomplicated primary total knee replacement the all-polyethylene PFC-∑ tibial prosthesis showed no statistical difference in migration from that of the metal-backed counterpart. There was no difference in the clinical results as assessed by the SF-12, the Oxford knee score, alignment or range of movement at 24 months, although these assessment measures were not statistically powered in this study.

Nanometre-sized particles of ultra-high molecular weight polyethylene have been identified in the lubricants retrieved from hip simulators. Tissue samples were taken from seven failed Charnley total hip replacements, digested using strong alkali and analysed using high-resolution field emission gun-scanning electron microscopy to determine whether nanometre-sized particles of polyethylene debris were generated in vivo. A randomised method of analysis was used to quantify and characterise all the polyethylene particles isolated.

We isolated nanometre-sized particles from the retrieved tissue samples. The smallest identified was 30 nm and the majority were in the 0.1 μm to 0.99 μm size range. Particles in the 1.0 μm to 9.99 μm size range represented the highest proportion of the wear volume of the tissue samples, with 35% to 98% of the total wear volume comprised of particles of this size. The number of nanometre-sized particles isolated from the tissues accounted for only a small proportion of the total wear volume. Further work is required to assess the biological response to nanometre-sized polyethylene particles.

We have undertaken a prospective study in patients with a fracture of the femoral shaft requiring intramedullary nailing to test the hypothesis that the femoral canal could be a potential source of the second hit phenomenon. We determined the local femoral intramedullary and peripheral release of interleukin-6 (IL-6) after fracture and subsequent intramedullary reaming.

In all patients, the fracture caused a significant increase in the local femoral concentrations of IL-6 compared to a femoral control group. The concentration of IL-6 in the local femoral environment was significantly higher than in the patients own matched blood samples from their peripheral circulation. The magnitude of the local femoral release of IL-6 after femoral fracture was independent of the injury severity score and whether the fracture was closed or open.

In patients who underwent intramedullary reaming of the femoral canal a further significant local release of IL-6 was demonstrated, providing evidence that intramedullary reaming can cause a significant local inflammatory reaction.

A modular layered acetabular component (metal-polyethylene-ceramic) was developed in Japan for use in alumina ceramic-on-ceramic total hip replacement. Between May 1999 and July 2000, we performed 35 alumina ceramic-on-ceramic total hip replacements in 30 consecutive patients, using this layered component and evaluated the clinical and radiological results over a mean follow-up of 5.8 years (5 to 6.5). A total of six hips underwent revision, one for infection, two for dislocation with loosening of the acetabular component, two for alumina liner fractures and one for component dissociation with pelvic osteolysis. There were no fractures of the ceramic heads, and no loosening of the femoral or acetabular component in the unrevised hips was seen at final follow-up. Osteolysis was not observed in any of the unrevised hips. The survivorship analysis at six years after surgery was 83%. The layered acetabular component in our experience, has poor durability because of unexpected mechanical failures including alumina liner fracture and component dissociation.

We present the histological findings of bone retrieved from beneath the femoral components of failed metal-on-metal hip resurfacing arthroplasties. Of a total of 377 patients who underwent resurfacing arthroplasty, 13 required revision; for fracture of the femoral neck in eight, loosening of a component in three and for other reasons in two. None of these cases had shown histological evidence of osteonecrosis in the femoral bone at the time of the initial implantation.

Bone from the remnant of the femoral head showed changes of osteonecrosis in all but one case at revision. In two cases of fracture which occurred within a week of implantation, the changes were compatible with early necrosis of the edge of the fracture. In the remaining six fractures, there were changes of established osteonecrosis. In all but one of the non-fracture cases, patchy osteonecrosis was seen.

We conclude that histological evidence of osteonecrosis is a common finding in failed resurfaced hips. Given that osteonecrosis is extensive in resurfaced femoral heads which fail by fracture, it is likely to play a role in the causation of these fractures.

We compared the performance of uncemented trabecular metal tibial components in total knee replacement with that of cemented tibial components in patients younger than 60 years over two years using radiostereophotogrammetric analysis (RSA). A total of 22 consecutive patients (mean age 53 years, 33 to 59, 26 knees) received an uncemented NexGen trabecular metal cruciate-retaining monobloc tibial component and 19 (mean 53 years, 44 to 59, 21 knees) a cemented NexGen Option cruciate-retaining modular tibial component.

All the trabecular metal components migrated during the initial three months and then stabilised. The exception was external rotation, which did not stabilise until 12 months. Unlike conventional metal-backed implants which displayed a tilting migration comprising subsidence and lift-off from the tibial tray, most of the trabecular metal components showed subsidence only, probably due to the elasticity of the implant.

This pattern of subsidence is regarded as being beneficial for uncemented fixation.

We examined the mechanical properties of Vicryl (polyglactin 910) mesh in vitro and assessed its use in vivo as a novel biomaterial to attach tendon to a hydroxyapatite-coated metal implant, the interface of which was augmented with autogenous bone and marrow graft. This was compared with tendon re-attachment using a compressive clamp device in an identical animal model. Two- and four-ply sleeves of Vicryl mesh tested to failure under tension reached 5.13% and 28.35% of the normal ovine patellar tendon, respectively. Four-ply sleeves supported gait in an ovine model with 67.05% weight-bearing through the operated limb at 12 weeks, without evidence of mechanical failure.

Mesh fibres were visible at six weeks but had been completely resorbed by 12 weeks, with no evidence of chronic inflammation. The tendon-implant neoenthesis was predominantly an indirect type, with tendon attached to the bone-hydroxyapatite surface by perforating collagen fibres.

We report an independent prospective review of the first 230 Birmingham hip resurfacings in 212 patients at a mean follow-up of five years (4 to 6).

Two patients, one with a loose acetabular component and the other with suspected avascular necrosis of the femoral head, underwent revision. There were two deaths from unrelated causes and one patient was lost to follow-up. The survivorship with the worst-case scenario was 97.8% (95% confidence interval 95.8 to 99.5). The mean Harris hip score improved significantly (paired t-test, p < 0.05) from 62.54 (8 to 92) pre-operatively to 97.7 (61 to 100) at a mean of three years (2.1 to 4.3), then deteriorated slightly to a mean of 95.2 (47 to 100) at a mean of five years. The mean flexion improved from 91.5° (25° to 140°) to 110.4° (80° to 145°) at a mean of three years with no further improvement at five years (111.2°; 70° to 160°).

On radiological review at five years, one patient had a progressive lucent line around the acetabular component and six had progressive lucent lines around the femoral component. A total of 18 femoral components (8%) had migrated into varus and those with lucent lines present migrated a mean of 3.8° (1.02° to 6.54°) more than the rest. Superolateral notching of the femoral neck and reactive sclerosis at the tip of the peg of the femoral component were associated with the presence of lucent lines (chi-squared test, p < 0.05), but not with migration of the femoral component, and are of unknown significance.

Our results with the Birmingham hip resurfacing continue to be satisfactory at a mean follow-up of five years.

Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.

The subject of central nervous system damage includes a wide variety of problems, from the slow selective ‘picking off’ of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system.

In an attempt to increase the life of cementless prostheses, an hydroxyapatite-coated implant which releases a bisphosphonate has been suggested as a drug-delivery system. Our in vitro study was designed to determine the maximum dose to which osteoblasts could be safely exposed.

Our findings demonstrated that zoledronate did not impair the proliferation of human osteoblasts when used at concentrations below 1 μm. Murine cells can be exposed to concentrations as high as 10 μm.

A concentration of 0.01% of titanium particles did not impair the proliferation of either cell line. Zoledronate affected the alkaline phosphatase activity of murine osteoblasts through a chelation phenomenon. The presence of titanium particles strongly decreased the alkaline phosphatase activity of murine osteoblasts. We did not detect any synergic effect of zoledronate and titanium particles on the behaviour of both human and murine osteoblasts.

The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors.

Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes.

There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism.