Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components. Human osteoblasts were obtained from the acetabulum and femoral neck of seven patients undergoing total hip arthroplasty (THA) and from the femoral and tibial cuts of six patients undergoing total knee arthroplasty (TKA). Osteoblasts were extracted from the usually discarded bone via enzyme digestion, characterized by flow cytometry, and cultured to passage three before measurement of metabolic activity, collagen production, alkaline phosphatase (ALP) expression, and mineralization.Aims
Methods
The aim of this study was to evaluate the role of peripheral blood derived mononucleated cells (PBMC) in osteochondral repair. We compared the healing of a critical size osteochondral defect in the medial femoral condyle and lateral trochlear sulcus in an ovine model.
Massive rotator cuff repairs have up to 60% failure rate and repair of a chronic repair can have up to 40% failure rate. With this in mind, new methodologies are being to being developed to overcome this problem. The use of tendon augmentation grafts is one of them. Prior attempts have shown equivocal or poorer outcomes to control repairs. Aims and objectives: The specific aim of these expereiments was to test how well ovine tendon cells would take to a specific biological augmentation graft (Ligamimetic), and wheter tissue engineering techniques would enhance this. Tendon cells harvested from ovine tendons will be cultured, exposed to the tendon augmentation graft, and analysed to see how well it takes to the tendon cells. We have conducted a 21 day experiment, sampling at days 7, 14, and 21. The experiment will look in sheep tendon cells:1. Platelet rich plasma: A comparison of the effects of platelet rich plasma to cell adherence, cell proliferation, and collagen production. Mesenchymal stem cell: A comparison of the effects of mesenchymal stem cells to the material on cell adherence, cell proliferation, and collagen production.Introduction
Method
Rotator cuff tears remain a problem, with massive tears having a failure rate of repair reported of up to 60%, despite advances in surgical techniques. Tissue engineering techniques offers the possibility of regenerating damaged tendon tissue to a pre-injury state. We explore these techniques by implanting two novel tendon augmentation grafts with use of platelet rich plasma (PRP) in sheep. A total of 24 sheep were operated on, with the infraspinatus being surgically cut from its attachment to the humeral head. Each tendon was repaired using suture anchors and an interpositional implant according to 4 groups: (1) Empty control, (2) Novel collagen fibre implant with PRP (3) A novel collagen sponge implant (4) and the collagen sponge with PRP. The sheep were killed at 12 weeks and the implant site harvested and its histology evaluated.Introduction
Methods
The MITCH PCR is an anatomic, flexible, horse-shoe shaped acetabular component, with 2 polar fins. The rationale of the PCR cup design is to reproduce a near-physiological stress distribution in the bone adjacent to the prosthesis. The thin composite cup is designed to fuse and flex in harmony with the surrounding bony structure. Only the pathological acetabular cartilage and underlying subchondral bone of the horseshoe-shaped, load-bearing portion of the acetabular socket is replaced, thus preserving viable bone stock. The PCR is manufactured from injection moulded carbon fibre reinforced polyetheretherketone (PEEK), with a two layer outer surface comprising hydroxyapatite and plasma sprayed commercially pure titanium. It is implanted in conjunction with a large diameter low wear femoral head, producing a bearing that will generate minimal wear debris with relatively inert particles. Pre-clinical mechanical testing, finite element analysis and biocompatibility studies have been undertaken. FEA evaluation predicts preservation of host bone density in the load bearing segments. A pilot clinical study was completed on a proto-type version of the PCR cup (the “Cambridge” cup), achieving excellent 5 and 10 year results. We report the three-year results from a two-centre, prospective clinical evaluation study of the MITCH PCR cup. Patient outcome has been assessed using standardised clinical and radiological examinations and validated questionnaires. The change in physical level of activity and quality of life has been assessed using the Oxford Hip Score, Harris Hip score and the EuroQol-5D score, at scheduled time-points. Serial radiographs have been analysed to monitor the fixation and stability of the components.Introduction
Subjects and Methods
Mesenchymal stem cells (MSCs) have potential for therapeutic repair of cartilage and bone but still require optimization in terms of their capacity to deposit an appropriate extracellular matrix (ECM). Adult human cartilage has a limited capacity for repair and is unusual in that it is one of the few tissues where injury is not followed by an influx of monocytes. We are studying the effects of co-culturing primary monocytes with MSCs differentiating along chondrogenic lineage but in addition we needed to investigate the effects of the monocytes on the mature chondrocytes that will result from the MSCs and will also be present in the host tissue. Human articular cartilage chondrocytes were isolated from human donors undergoing knee replacement surgery for osteoarthritis (OA) with full ethical consent. Cultures were expanded and cells used below passage five for co-culture experiments. Monocytes were prepared from fresh heparinized human blood samples by Ficoll gradient. Co-cultures consisted of either chondrocyte micromasses overlaid with monocytes, or chondrocytes and monocytes seeded together within a collagen/glycosaminoglycan scaffold (Chondromimetic, Tigenix UK). Media, cell pellets and scaffolds were analysed for extracellular matrix (ECM) proteins and proteases by dot blot, western blot, zymography and immunohistochemistry. Human chondrocytes maintained stable micromasses and laid down an ECM for at least 40 days. Human monocytes eventually formed a proliferating cell population with a rounded morphology on top of the chondrocyte micromasses. These cells established an adherent population with a fibroblastic morphology when replated on plastic. Analysis of chondrocyte ECM proteins indicated that monocytes affected deposition of types I and II collagen, decorin and fibronectin and the overall amounts of gelatinases released. RTPCR demonstrated a decrease in type I collagen expression and a concomitant increase in MMP13 expression. The precise interaction between monocytes and and chondrocytes has yet to be established but is thought to involve a mixture of contact and paracrine factors. In this study co-culture of monocytes with chondrocytes resulted in phenotypic changes to the chondrocytes which may warrant the inclusion of monocytes in cartilage/bone repair and also provide information as to the responses of OA chondrocytes to external stimuli.
Mesenchymal stem cells (MSC) are an attractive cell population for regeneration of mesenchymal tissue such as bone and cartilage. Various studies have demonstrated the repair capacity of MSCs and even their usefulness in treating critical size defects. Much of the work conducted on adult stem cells has focused on MSCs found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. The aim of the present study is to evaluate the differentiation capability of adipose-tissue derived stem cells (ASC) extracted from the infrapatellar fat pad. Human infrapatellar fat pad tissue was obtained from patients undergoing total joint replacement for osteoarthritis with full ethical consent. A multipotent progenitor cell population was derived after collagenase digestion from the adipose tissue. The ASCs were induced to differentiate towards adipogenic, chondrogenic, and osteogenic lineages for 21 days both in normoxic and hypoxic cell culture conditions. The differentiation and multilineage potential was assessed according to cell morphology and in vitro detection of tissue-specific differentiation molecules.Introduction
Materials and Methods
Porous collagen-glycosaminoglycan (Col/GAG) scaffolds have previously been used clinically as regeneration templates for peripheral nerves and skin[1]. For defects involving even minimal load-bearing applications however, these scaffolds do not possess the required stiffness. Calcium phosphates (CaPs) are often used as bone-graft substitutes due to their biocompatibility and direct bone-bonding ability. While CaPs have sufficient stiffness for bone-defect applications, unlike Col/GAG they lack elasticity and are very brittle. Combining these two materials produces a composite with enhanced material properties and chemical similarity to natural bone. The addition of CaP nanocrystallites into the Col/GAG matrix produces a 3-dimensional structure that maintains its structural integrity even when wet. In this study, the in vivo performance of mineralised Col/GAG composites was evaluated by implantation into a six-week ovine bone-defect model. Four different materials were implanted; Col/GAG alone, Col/GAG with octacalcium phosphate, Col/GAG with hydroxyapatite and Col/GAG with brushite. Implants with a diameter of 9mm and length of 9mm, were placed bilaterally into the distal femoral condyle of the hind legs of thirteen sheep. This site was selected due to the large volume of load-bearing cancellous bone. Cancellous autograft was harvested from the tibial tuberosity and placed in the defect sites of two sheep as a positive control. All animals were sacrificed after 6 weeks and tissue containing the implants was prepared for histological evaluation. Image analysis of Von Kossa stained sections showed that all mineralised Col/GAG implants had significantly more bone in the implant site than unmineralised Col/GAG but were not significantly different between CaPs. Interestingly, new bone formation often followed the structure of the porous material struts which acted as a template. The defect containing the autograft contained the greatest amount of new bone. The inclusion of mineral substantially improves the osteoconductivity of Col/GAG. No significant difference between the different calcium phosphates was seen. Whilst these materials did not stimulate bone formation to the same extent as autograft, many bone graft procedures are carried out with allograft which performs less favourably.Conclusions
Maintaining femoral neck cortical thickness may help prevent hip fracture. Fracture initiation probably starts superiorly at flaws, ie where the cortex is thinnest. Whole body computed tomography (QCT) is now being used to study cortical thickness but limited resolution (> 300 micrometers) makes in vivo estimates imprecise, whereas microscopy s resolution approaches 1 micrometer. We have therefore extended our microscopic studies on femoral neck biopsies to include men (14 cases, 26 controls) and women (50 cases, 23 controls), and here provide data on true cortical thickness in subjects with and without hip fracture. Whole femoral neck cross-sections obtained at hemiarthroplasty (or at post-mortem in controls) were embedded in methacrylate, cut, stained and imaged at medium power. Image-J was used to define cortical boundaries and to measure cortical thicknesses at 5 degree intervals of arc from the cross-sections centre of area. We confirmed that the mid-femoral neck (or narrow neck) site, defined as where the ratio of maximum to minimum neck diameter (max:min) is 1.4, shows great asymmetry, with the thick inferior cortical octant averaging over 3mm thickness (mean age 79 years inter-quartile range 74-85). In the superior 3 octants cortical thickness averaged 26% of that seen inferiorly. To assess statistical determinants of cortical thickness, the data were modelled with linear regression in octants after adjusting for subjects age, sex, max:min, and hip fracture status. To achieve normality of residuals the cortical thickness data were log-transformed. 95% of measured cortical thicknesses fell between 45% and 220% of the mean for octant. In the thinner, superior three octants, minimum thicknesses were just under 0.3 mm in the fracture cases ie close to 35% of the subjects mean for octant. Cases had about 17% thinner cortical thicknesses in all octants than controls, while female controls had cortical thicknesses that uniformly averaged 90% of male. In conclusion, compared to gender and age-matched controls, intra-capsular hip facture cases had generalized cortical thinning in all mid-neck octants. This disease effect contrasts markedly with the effect of normal ageing, which thins preferentially the mechanically under-loaded superior cortex and spares the infero-anterior cortex.
Meniscal cartilage provides joint stabilisation, load distribution, impact absorption and decreased friction in joints that have a complex movement such as the knee. If the meniscal cartilage degrades or is surgically removed, there is a strong probability, over time, of damage to the articular surface. The ability to regenerate damaged meniscal cartilage with an implanted device that replaces the biological equivalent would allow for joint stabilisation, robust movement and reduce the risk of damage to the articular cartilage. An implant with many of the characteristics of meniscus and with the ability to integrate correctly and firmly with the surrounding tissue, would be advantageous. Inclusion of Platelet Rich Plasma (PRP) into the scaffolds to provide a concentrated source of matrix proteins and autologous growth factors may further enhance the regenerative repair process. To investigate the suitability of the collagen scaffolds, addition of meniscal chondrocytes and or PRP was examined in vitro. Human meniscal chondrocyte cells were isolated, via collagenase digestion, from meniscal cartilage recovered from total knee replacement surgery. Meniscal chondrocytes were cultured in vitro to expand cell numbers. PRP was produced from volunteer's blood using a centrifuge and density based platelet recovery system. Release of Platelet Derived Growth Factor type AB (PDGF-AB) was measured by ELISA as an indicator of the behaviour of the peptide growth factor component. Combinations of scaffold, meniscal chondrocytes and PRP were tested for interaction, suitability and viability. Experiments so far have shown good biocompatibility, in vitro, as meniscal chondrocytes were able to grow within the range of scaffolds produced. Cell retention could be enhanced by addition of PRP to the scaffolds. PDGF-AB was released over 5 days from the scaffold and PRP combination. Further studies are in progress to derive relevant scaffold modifications and combinations for practical, robust, treatment strategies.
The aseptic loss of bone after hip replacement is a serious problem leading to implant instability. Hydroxyapatite coating of joint replacement components produces a bond with bone and helps to reduce loosening. However, over time bone remodeling at the implant interface leads to loss of hydroxyapatite. One possible solution would be to develop a coating that reduces hydroxyapatite and bone loss. Hydroxyapatite can be chemically modified through the substitution of ions to alter the biological response. Zinc is an essential trace element that has been found to inhibit osteoclast-like cell formation and decrease bone resorption. It was hoped that by substituting zinc into the hydroxyapatite lattice, the resultant zinc-substituted hydroxyapatite (ZnHA) would inhibit ceramic resorption and the resorption of bone. The aim of this work was to investigate the effect of ZnHA on the number and activity of osteoclasts. Discs of phase pure hydroxyapatite (PPHA), 0.37wt% ZnHA and 0.58wt% ZnHA were produced, sintered at 1100 degrees Celsius and ground with 1200 grit silicon carbide paper. They were cultured in medium containing macrophage colony stimulating factor and receptor activator of nuclear factor kappa B ligand (RANKL) for 11 and 21 days. A control disc of PPHA cultured in medium containing no RANKL was also used. On the required dates the discs were removed and the cells stained for actin with phalloidin-TRITC and the cell nuclei with 4',6-Diamidino-2-phenylindole dihydrochloride. Cells with 3 or more nuclei were classed as osteoclasts and counted using ImageJ. On day 21 after the cells had been counted, the cells were removed and the discs coated in platinum before viewing with a scanning electron microscope. Resorption areas were then measured using ImageJ. The addition of zinc was observed to significantly decrease the number of differentiated osteoclasts after 21 days (p<0.005 for 0.58wt% ZnHA compared to PPHA and p<0.01 for 0.37wt% ZnHA compared to PPHA). The area of resorption was also significantly decreased with the addition of zinc (p<0.005 for the comparison of 0.58wt% ZnHA with PPHA) The work found that zinc substituted hydroxyapatite reduced the number and subsequent activity of osteoclasts.
Mechanical trauma to articular cartilage is a known risk factor for Osteoarthritis (OA). The application of single impact load (SIL) to equine articular cartilage is described as a model of early OA changes and shown to induce a damage/repair response. Recombinant Human Fibroblast Growth Factor-18 (rhFGF-18) has been previously shown to have anabolic effects on chondrocytes in vitro. The aim of this in vitro study was to ascertain the effect of rhFGF-18 on the repair response of mechanically damaged articular cartilage. Articular cartilage discs were harvested from healthy mature horses (n=4) and subjected to single impact load using a drop tower device. The impacted explants, together with unimpacted controls were cultured in modified DMEM +/− 200ng/ml rhFGF-18 for up to 30 days. Glycosaminoglycan (GAG) release into the media was measured using the dimethylmethylene blue (DMMB) assay, aggrecan neopepitope CS846 and Collagen Propeptide II (CPII) were measured by ELISA. Histological analysis, immunohistochemistry and TUNEL staining were used to assess proteoglycan content, type II and type VI collagen localisation, cell morphology, repair cell number and cell death.Background
Methods
There is increasing application of bone morphogenetic proteins
(BMPs) owing to their role in promoting fracture healing and bone
fusion. However, an optimal delivery system has yet to be identified.
The aims of this study were to synthesise bioactive BMP-2, combine
it with a novel α-tricalcium phosphate/poly(D,L-lactide-co-glycolide)
(α-TCP/PLGA) nanocomposite and study its release from the composite. BMP-2 was synthesised using an Objectives
Methods
In vitro femoral studies have demonstrated the addition of hydroxyapatite (HA), to morcellised bone graft (MBG) decreases femoral prosthesis subsidence. However, with an increased risk of femoral fracture during the impaction of a MBG:HA mixture, possibly due to greater force transmission to the femoral cortex via the HA. The aim was to compare the hoop strains and subsidence of a 1:1 mixture of MBG:HA with pure bone allograft during impaction and subsequent endurance testing in a revision hip arthroplasty model. Materials and methods Large Sawbone femurs were prepared to represent a femur with bone loss (Sawbones, Sweden). 12 uniaxial strain gauges were attached to each femur at 0, 90, 180 and 270 degrees, at distal, midshaft, proximal points to measure hoop strain. Impaction grafting was performed using X-Change 2 instruments and an Instron servohydaulic machine for 2 distal impactions and 4 proximal impactions for 60 impactions each. The study consisted of four experimental groups: 1)Pure MBG, force of 1.98 kN 2)Pure MBG, force 3.63kN. 3)1:1 mixture of MBG: porous HA (pHA), 4)1:1 mixture MBG: non porous HA (npHA). 6 samples of each group were performed. The potted femur was loaded in a manner representing the walking cycle (1.98kN) at 1 Hz for 50 000 cycles. The displacement of the femoral head during loading was measured by two displacement transducers (LVDT) were mounted on aluminum brackets to measure vertical displacement and rotation.Study groups
Endurance testing
The annual incidence of fractures in the UK is almost 4%. Bone grafting procedures and segmental bone transport have been employed for bone tissue regeneration. However, their limited availability, donor site morbidity and increased cost mean that there is still a large requirement for alternative methods and there is considerable research into regeneration using bone morphogenetic proteins (BMPs). The aims of this study are to synthesise and combine BMP-2 with a novel nanocomposite and study its release. BMP-2 was synthesised using an E. coli expression system and purified. C2C12 cells were used to test its bioactivity using an alkaline phosphatase (ALP) assay. The modified solution evaporation method was used to fabricate 30% a-TCP/PLGA nanocomposite and it was characterized using SEM, TEM, TGA, XRD, EDX and particle size analysis. The release pattern of adsorbed BMP-2 was studied using an ELISA assay.Introduction
Materials and Methods
Problems associated with allograft are well known. The addition of hydroxyapatite (HA) to allograft has various mechanical advantages, especially within revision arthroplasty. The mixing of bone and HA results in mechanical properties different from the individual parts. However, at present the changes in material properties the mix have not been fully investigated and the optimum mixing ratio not characterized. A compressive uniaxial chamber was used to investigate the change in mechanical properties occurring with the addition of HA in varying proportions to morcellised bone graft (MBG). MBG was prepared using femoral heads donated from patients undergoing total hip replacement surgery using a bone mill in a standard manner. Non porous HA (npHA) was prepared using a precipitation method of Calcium Carbonate and Orthophosphoric acid. The porous HA, (pHA) is a 60% macroporosity HA commercially prepared. The uniaxial compression chamber was a 30mm diameter, steel chamber. Holes were drilled to allow fluid drainage. Loads were applied using a 10 kN load cell. Specimens were prepared in the volumetric proportions pure HA, pure MBG, 2:1, 1:1, 1:2 ratio of MBG to HA. The samples were subjected to compressive forces of incrementally increasing loads of up to 2 KN for 60 cycles. The sample was then allowed to creep under a stress of 2 kN. MBG was also tested up to forces of 7 kN. The mechanical parameters that were examined were the stiffness of the sample at the 60th cycle, (Ec60), and creepMaterials and methods
Chamber
The purpose of this study was to investigate whether combining PRP or concentrated bone marrow aspirate (CBMA) with a biphasic collagen/glycosaminoglycan (CG) scaffold would improve the outcome of the treatment of full thickness osteochondral defects in sheep. Osteochondral defects (5.8×6mm) were created in the medial femoral condyle (MFC) and the lateral trochlea sulcus (LTS) of the stifle joints of 24 sheep. Defects were either left empty or filled with a 6×6mm CG scaffold, either on its own or in combination with PRP or CBMA (n=6). At 6 months the sheep were euthanised, and the repair tissue subjected to mechanical testing, gross morphological analysis, semi quantitative histological scoring and immunohistochemical staining including types I, II and VI collagen.Introduction
Materials and Methods
The HA coated implants remained asymptomatic. Three uncoated components required revision for migration. No evidence of accelerated UHMWPE wear was seen on retrievals or radiographs. Histological analysis of the retrieved HA coated specimens showed excellent bony fixation, uncoated cups showed predominantly fibrous tissue.
The aim of this study was to show the efficacy of Chondromimetic in repairing a surgically created osteochondral defect in a caprine model.
The aim of this study was to ascertain whether the addition of thrombin is required to achieve platelet activation and sustained growth factor release in-vitro, when PRP is applied to a collagen based osteochondral scaffold.
The influence of the timing of surgery for closed ankle fractures on complications is unclear. Previous studies have failed to demonstrate any associations with clear statistical support. This is a retrospective review of 221 patients presenting with closed ankle fractures treated with open reduction and internal fixation. The patients were similar in respect to age, gender, fracture type, surgeon grade, American Society of Anaesthesiologists grade, grade of anaesthetist and tourniquet time. Power analysis was performed for sample size. Patients were followed up until fracture union. The mean duration of inpatient care was greater in the delayed group (
There has been renewed interest in metal-on-metal bearings as hip resurfacing components for treatment in young, active patients. This study examines the effects of fixation (cemented or uncemented heads) and bone-implant interface conditions (stem-bone and head-bone) on the biomechanics of the Birmingham hip resurfacing (BHR) arthroplasty, using high resolution, 3-d computational models of the bilateral pelvis from a 45-year-old donor. Femoral bone stress and strain in the natural and BHR hips were compared. Bone remodelling stimuli were also determined for the BHR hips using changes in strain energy. Proximal femoral bone stress and strain were non-physiological when the BHR femoral component was fixed to bone. The reduction of strain energy within the femoral head was of sufficient magnitude to invoke early bone resorption. Less reduction of stress was demonstrated when the BHR femoral component was completely debonded from bone. Bone apposition around the distal stem was predicted based on the stress and strain transfer through the stem. Femoral stress or strain patterns were not affected by the type of fixation medium used (cemented vs. Uncemented). Analysis of proximal stress and strain shielding in the BHR arthroplasty provides a plausible mechanism for overall structural weakening due to loss of bony support. It is postulated that the proximal bone resorption and distal bone formation may progress to neck thinning as increasing stress and strain transfer occurs through the stem. This may be further exacerbated by additional proximal bone loss through avascular necrosis. Medium term retrieval specimens have shown bone remodelling that is consistent with our results. It is unclear if the clinical consequences of neck thinning will become more evident in longer-term follow-ups of the BHR.
One potential limitation with uncemented, hemispherical metal-backed acetabular components is stress shielding of bony structures due to the mismatch in elastic modulus between the metal backing and the peri-prosthetic bone. A proposed substitute is a horseshoe-shaped acetabular component, which replicates the bony anatomy. One such device, the Cambridge cup, has shown successful clinical and radiological outcomes at five years follow-up (Brooks 2004, Field 2005). We conducted a study of the Cambridge cup from a biomechanical perspective, using validated, high-resolution computational models of the bilateral hip. Peri-prosthetic stress and strain fields associated with the Cambridge cup were compared to those for the natural hip and a reconstructed hip with a conventional metal-backed hemispherical cup during peak gait loading. We found that the hemispherical cup caused an unphysiologic distribution of bone stresses in the superior roof and unphysiologic strain transfer around the acetabular fossa. These stress distributions are consistent with bone remodelling. In contrast, the peri-acetabular stresses and strains produced by the Cambridge cup differed from the natural hip but were more physiologic than the conventional hemispherical design. With the Cambridge cup, stresses in the superior acetabular roof, directly underneath the central bearing region, were greater than with the conventional design. Despite the thin bearing, the peak liner stresses in the Cambridge cup (max. tensile stress: 1.2 MPa; yield stress: 4.5 MPa) were much lower than the reported material strengths. Fossa loading by the hemispherical cup has been suggested as a possible mechanism for decreased implant stability (Widmer 2002). Conversely, the Cambridge cup produced semi-lunar peri-prosthetic stress fields, consistent with contact regions measured in natural hips (Widmer 2002). These analyses provide a better understanding of the biomechanics of the reconstructed acetabulum and suggest that a change in component geometry may promote long-term fixation in the pelvis.
Prior studies have compared the bacterial load observed in laminar flow operating theatres (LFOTs) and standard operating theatres (STOTs) by wound culture and air sampling during surgery. However many organisms responsible for low grade infection after THR are not readily identified on routine culture and may be detectable only by more sensitive techniques such as the poly-merase chain reaction (PCR). This study assessed the wound contamination rate during THRs and compared the results in STOT with that in LFOTs using PCR. We recruited patients undergoing primary THR for osteoarthritis. Surgery was performed in either STOTs or LFOTs, using identical skin preparation solutions, surgical drapes and operating attire. Specimens of the deep tissue, taken at the beginning and end of surgery, were each immediately separated into two sterile containers, one sent for culture (aerobic, anaerobic and enriched meat broth) and the other frozen at minus 80 degrees Celsius for PCR at a later date. In each theatre type, 40 specimens from 20 THRs were analysed by both PCR and culture. Using PCR, bacterial DNA was identified on 12 of 40 specimens (30%) from STOTs, of which 3 were taken at the start of surgery and 9 at the end of the surgery, giving a 45% wound contamination rate (9 of 20). Two specimens (5%), both taken at the end of surgery, were positive on enriched culture. In LFOTs, bacterial DNA was identified by PCR on 8 of 40 specimens (20%), of which 2 were taken at the start of surgery and 6 at the end of surgery, giving a 30% wound contamination rate (6 of 20). No specimens were positive on enriched culture. Wound contamination of primary THR occurs frequently in both STOTs and LFOTs. Although STOTs showed evidence of more frequent wound contamination than LFOTs, with the numbers available, no significant difference was detected. These data remind us the importance of aseptic surgical technique as significant wound contamination can occur despite the use of ultra clean air operating theatres.
This study examines the effect of injecting an inert synthetic lubricant, perfluoroalkylether (PFAE16350), as a mechanical joint lubricant to prevent the development of osteoarthritis in a surgically induced model of osteoarthritis in the adult guinea pig.
After wound closure, the animals were randomly assigned to 1 of 2 groups: (1) Single intra-articular injection of 1ml synthetic, sterile lubricant (PFAE16350) or (2) Control group with single intra-articular injection of 1ml 0.9% sterile saline. At 9 weeks after surgery, after sacrifice, knee arthrotomy was performed, the presence of synthetic lubricant noted and the articular cartilages examined for macroscopic evidence of osteoarthritis. These cartilages were then fixed, embedded, sectioned, stained and graded histologically for osteoarthritis according to a modified Mankin scoring system. Immunohistochemical studies were performed to assess for any inflammatory or cytotoxic effect by the lubricant.
Subjective macroscopic assessment of the medial tibial plateau osteophyte was noted to be larger and the articular surface more roughened in the control cases compared to the lubricated cases. Synthetic lubricant was noted at arthrotomy in all cases where it was injected. Guinea-pig joints treated with the synthetic lubricant showed a mean modified Mankin score of 3.0 points compared with the guinea-pig joints treated with saline where the median modified Mankin score was 8.5 points (p<
0.001). There was no evidence of an inflammatory or cytotoxic response by immunohistochemical studies.
Using PCR, bacterial DNA was identified on 12 of 40 specimens (30%) from STOTs. Of these 12, three were taken at the start of surgery and nine at the end of the surgery, equivalent to a 45% wound contamination rate (9 of 20). Only two specimens (5%), both taken at the end of surgery, were positive on enriched culture. In LFOTs, bacterial DNA was identified by PCR on eight of 40 specimens (20%). Of these eight, two were taken at the start of surgery and six at the end of surgery, equivalent to a 30% wound contamination rate (6 of 20). None of the specimens were positive on enriched culture.
Research is the quest for information. It is not an excuse for attending meetings in exotic places, nor is it an escape from clinical work that has become uninteresting. The early orthopaedic joumals contained reports of patients who have been treated by individual surgeons in specific, often novel, ways. There was little scientific structure, but nevertheless these papers were valuable as they disseminated knowledge to other Surgeons and also stimulated enquiry. Orthopaedic research has developed dramatically over the last two or three decades. Patient related research has been advanced as a result of the availability of new techniques for example electron microscopy, DNA sequencing and the Genome, together with the discovery of the fine details of the cytokine control of cellular processes. This has gone hand in hand with the development of surgical sophistication allowing more adventurous interventions. Joint replacement and internal fixation have led to close associations between orthopaedic surgeons and scientists from other disciplines, notably engineers and material scientists. This multi-disciplinary involvement is typical of orthopaedic surgeons and results in each discipline benefiting from the specialist knowledge of the others. The natural tendeney for orthopaedic surgeons to be interested in mechanical items is clear from a study of the distribution of interesting cars in the hospital car park! The efficacy of different treatment methods should be challenged and this has resulted in the need for careful audit and epidemiological review. In some instances this has resulted in the conclusion that often used treatments are not effective. The assiduous application of the Cochrane principles is often very revealing, not least in that it indicates the lack of properly conducted orthopaedic trials. Academic orthopaedics is in danger. In many countries the speciality is under pressure, normally as a result of economic measures that restrict the avallability of salarles and grants. In spite of these restrictions, it is surprising that there is a steady supply of excellent papers. How much better it could be with more funding. The purpose of publícation is to share information. It should be the aim of every research worker to make a contribution to the understanding of the subject and to share his findings with his colleagues. Curiously many researchers feeI that their commitment to their project is complete as soon as they finish the trial and have the results. The preparafion of their work for dissemination through publication is often a very weak link and in some instances is absent. This is a dangerous tendency as their information may not be broadcast, wasting the scientific endeavour and endangering the status of the fundíng organisation, whose charitable status often depends on sharing the fruitg of research. The incentive to publish is very variable. In some institutions the very existenee of a research department depends on a ‘paper score’ which is normally calculated from the product of the number of papers and the impact factor of the j ournal in which they are published. The calculation used to determine the impact factor of ajournal does not favour orthopaedic journals, as most orthopaedic papers are not quoted prolifically within the first year of publication. In contrast orthopaedic papers tend to have a much longer and more valuable lifetime and to some this is the more important and relevant feature. Unfortunately, the long-term value of the papers is not part of the calculation of impact factor. In order to achieve a high impact factor the publication must be in a rapidly changing field and contain at least a tiny element of special originality, which leads to it being quoted by most of the workers in that field. In the publishing world there is an ongoing discussion conceming an index that is more relevant than the impact factor. For some, the competition for publication is so intense that there is ‘salami slicing’. Salami slicing is a process of publishing very small morsels of information in short papers instead of producing the complete study. It is done intentionally to increase the number of papers published and is frowned upon by scientific editors. Even worse there are cases of plagiarism and fraud, sadly occurring more commonly in surgical publication, than in other disciplines. It may be time to ask fundamental questions about the need for research, articularly the need for every doctor in training to improve or embellish his or her Curriculum Vitae by decorating it with published works. There ís a tendeney for the more wealthy and better respected grant awarding bodies to fund successful rescarch teams, rather than to risk their limited resources on a spectacular project from an unknown team. Funding is avallable from commercial sources. The role of this type of rescarch may require special assessment. There are issues of intellectual property rights and instances of commercial organisations delaymg or preventing publication if the findings of the study are not favourable. Many cynical readers give no weight to papers that are sponsored by commercial sources. It is essential that rescarch in orthopaedics continues and that every possible step is taken in order to facilitate high quality research. There may be strength in numbers and it could be that the newly revitalised European Orthopaedic Research Society could help in supporting the endeavours of rescarch workers, particularly when it comes to European funding.
Radiographic results showed no evidence of loosening of HA coated cups, in contrast to non HA coated cups which migrated significantly in 80% of cases. Four patients with loose non HA coated cups underwent revision surgery.
The novel horseshoe shaped cup was designed by the senior authors to minimise the resection of healthy bone in total hip arthroplasty. It replaces the cartilage and underlying sub-chondral bone of the acetabulum socket with a cup that is designed to flex in harmony with the surrounding bony structure. Fifty female patients with a displaced, subcapital, femoral neck fractures were chosen for the study. In half of the group of patients, the composite support shell was coated with HA, with the other half remaining uncoated. Clinical and radiological assessments were undertaken regularly for five years. To date 20 patients have died and 13 have withdrawn from the study due to poor medical health unrelated to the study. Charnley modified Merle d’Aubigne score at five years was as good as the preoperative score with 80% of patients having full range of movement, no pain and walking unaided. Radiographic results showed no evidence of loosening of HA coated cups, in contrast to non HA coated cups which migrated significantly in 80% of cases. Four patients with loose non HA coated cups underwent revision surgery. This trial has demonstrated success at 5 years with the HA coated Cambridge Acetabular Cup. Cups from which HA coating has been removed have migrated significantly in 80% of cases. There is an advantage of the HA fixation which will be taken into account before wider clinical usage is advocated.
Radio-pacifiers in bone cements are an accepted part of every-day practice. They have, however, been shown to be a potential cause of an increase in third body wear and to excite bone resorption We reviewed the results of 228 consecutive Stanmore Total Hip Replacements performed between 1981 and 1985 in 211 patients. All were inserted with radiolucent bone cement. Information regarding whether the prosthesis had been revised was available for all patients. 73 patients (83 hips) were still alive and 41 patients (44 hips) were sufficiently healthy to attend clinic. Information regarding pain level was obtained from the remaining 32 patients. When revision of the implant was taken as the end-point, there was 95% ten-year survival, 91% fifteen-year survival and 75% eighteen-year survival. These long-term results of Stanmore THRs, performed in a district general hospital, with radiolucent bone cement, compare favourably with the other published series for this implant. We did not find the inability to see the bone cement a particular disadvantage when reviewing x-rays for signs of loosening.
Differentiating cases of aseptic loosening of total hip arthroplasty (THA) from loosening due to low-grade infection can often be difficult. It is possible that some cases of ‘aseptic’ loosening may be related to unidentified bacterial infection. Using Polymerase Chain Reaction (PCR), this study attempted to identify the frequency with which bacterial DNA could be observed at revision arthroplasty for what was considered ‘aseptic’ loosening. All revision cases had to fulfil strict criteria to be considered aseptically loose In all cases operative specimens from the synovial fluid, synovium, femoral and acetabular membranes where possible were sent for analysis by histology, bacteriology and by PCR to identify the presence of the 16S bacterial ribosomal fraction, an indicator of bacterial DNA. Ten bacteria per millilitre of tissue/fluid were the threshold for detection. As a control for environmental contamination, specimens from primary THA were also sent for analysis in the same manner as revisions. The identification of bacterial DNA in at least one sample from a patient was considered a positive case result. 45 revision THA were identified over a 3-year period (1998–2001). From those 45 revision cases, 163 specimens were sent for analysis by PCR. These specimens were compared to the control group of 34 primary THA from which 91 specimens were sent for analysis by PCR. When analysed by specimens positive by PCR, bacterial DNA was identified in 55 of 163 specimens sent from the 45 revision THA. This compared with 21 of 91 specimens positive by PCR sent from the 34 primary THA (p=0. 07). When analysed by cases positive by PCR, bacterial DNA was identified in 29 of 45 revision THA and in 8 of 34 primary THA (p<
0. 001). PCR is a sensitive test for detecting infection in revision THA. Results from the primary THA cases would suggest there is at least a 23% false positive rate even with negative bacterial culture. The increased frequency with which bacterial DNA has been identified in ‘aseptically’ loose revision THAs, however, is unlikely to be due solely to environmental contamination. These results may have relevance for our interpretation and understanding of aseptic loosening as well for the diagnosis of prosthetic infection.
The use of musculo-skeletal MRI is increasing at spectacular rate, however there have been few rigorous evaluations of its’ clinical effectiveness. This study was conducted to assess the impact of MRI of the wrist on clinical diagnosis and patient management. A controlled observational study was performed, in which referring clinicians completed questionnaires on diagnosis and intended management before and after wrist MRI. We analysed 118 consecutive patients referred for MRI of the wrist, to the magnetic resonance imaging units at a regional teaching hospital and a large district general hospital. We assessed: changes in clinicians’ leading and subsidiary diagnoses after MRI; their certainty of these diagnoses; and changes in intended patient management. Five patients had incorrectly completed requests, ten cancelled their appointments and two could not tolerate the MR examination. Complete follow up data is available for 98/101 patients with correctly completed request forms who were examined. The clinical diagnosis changed in 55 of 98 patients (56%). Diagnostic certainty increased in 23 of the remaining 43 patients (53%). Clinicians reported that MRI had substantially improved their understanding of the patients’ disease in 67/98 (68%) patients. There was a change in management in 46/98 (47%) patients, with a shift away from operative treatment. 28 out of 98 (29%) patients were discharged without further investigation. MRI was similarly effective in a regional teaching centre and a district general hospital. Magnetic resonance imaging of the wrist influences clinicians’ diagnoses and management plans. These results demonstrate the clinical effectiveness of MRI of the wrist in both a regional teaching centre and a district general hospital.
This study investigated the effects of wear particles, produced from a number of implant materials, at the bone-implant interface using a small animal model. Particles were prepared from metal, ceramic and polymer replacement joint components or implant grade stock by grinding the materials against a diamond embedded grinding pad. The mean diameter of the particles ranged from 1.5mm to 3.2mm. Sterilised particles were suspended in sterile saline containing 2% v/v male Sprague-Dawley serum at a concentration of 109 particles per ml. Seventy-two male Sprague-Dawley rats were assigned to twelve groups of six animals. A ceramic pin was inserted into the right tibia of each animal. Six groups were assigned a particle type with one group acting as vehicle control. 100ml of particle suspension or vehicle was injected into each knee joint at 8, 10 and 12 weeks following implantation and the animals were killed 2 weeks later. Of the remaining five groups, four were assigned a particle type and one was the vehicle control. These animals were injected with 100ml of particle suspension or vehicle at 20, 22 and 24 weeks following pin implantation and were killed 2 weeks later. The tibia and femora were removed, disarticulated and processed for histology. The total gap between pin and bone, including fibrous tissue, was measured. Specimens showed no signs of infection either clinically or in the histopathology. All materials tested produced lesions at the bone-implant interface. A significant difference was seen between metal injected vs. vehicle control animals and aluminium oxide injected vs. vehicle controls. Particles of stainless steel produced the greatest response and this finding may have implications for the use of metal on metal articulations aimed at eliminating polyethylene wear.
This study investigated the relationship between histological, clinical and radiological features of aseptically loose total joint replacements (TJRs) and synovial fluid levels of interleukin (IL)-1b, IL-6, IL-8 and IL-10. Tissue and synovial fluid samples were retrieved from patients undergoing primary (hip; n=15: knee; n=13), or revision of aseptically loose TJRs (hip; n=14: knee; n=9). The presence of inflammatory cells, blood vessels and wear debris in the tissue were assessed on a relative scale. Revision TJRs were assessed for sepsis, migration of the implant, gross loosening and the degree of radiolucency. Cytokine levels in the synovial fluid samples were determined by ELISA. All cytokines were increased in synovial fluid from revision TJRs compared to primary replacements, as were the degree of macrophage and giant cell infiltration (p<
0.01). There was a significant positive correlation between the presence of macrophages and giant cells with the levels of IL-1b, IL-8 and IL-10 (p<
0.05) but not IL-6. The amount of wear debris was related to the presence of macrophages and giant cells (p<
0.01) but not to any of the cytokines. There were no relationships between any of the clinical parameters and the presence of wear debris or the levels of any cytokine with the exception of IL-6 and gross loosening (p<
0.01). Similarly there were no differences between hips and knees for any of the parameters except IL-6, for which higher levels were found in hips (p<
0.05). The results suggest that macrophages and giant cells are responsible for the majority of IL-1b, IL-8 and IL-10 production but another cell type is contributing to IL-6 production. Furthermore, IL-6 does not fit the pattern of the other cytokines as it is upregulated in hip joints compared to knees and correlates with the presence of gross loosening. This may suggest a unique role for IL-6 that requires further investigation.