Aim. Diagnosis of prosthetic joint infection are often complicated by the presence of biofilm, which hampers bacteria dislodging from the implants, thus affecting sensitivity of cultures. In the last 20 years several studies have evidenced the usefulness of implant sonication to improve microbial recovery from biofilm formed on inert substrates. More recently, treatment of prosthetic joints and tissues with Dithiothreitol, a sulphur compound already used in routine diagnostic workflow for fluidification of respiratory samples, has proved to be not inferior to sonication in microbiological diagnosis of prosthetic joint infections. This study aimed to evaluate if the combination of the two treatments could further improve microbial retrieval from biofilm in an in vitro model. Method. Three isolates of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Eschericha coli and Pseudomonas aeruginosa responsible of prosthetic joint infections were used. They were grown onto 3 titanium discs (20 mm diameter) and incubated in 3 sterile plastic containers with 15 mL of Triptyc Soy Broth. After overnight incubation, not adhered cells were removed and fresh broth was added to each sample. After 48 hours incubation, the exausted broth was removed and one sample was used for sonication, one for treatment with 0,1% (v:v) Dithiothreitol and one treated with Dithiothreitol followed by sonication. Treated fluids were plated on Muller Hinton Agar plates for colony count. One-way ANOVA analysis was performed to evidence statistical differences between treatments. Results. Similar colony counts were observed for the 3 treatments: 10.1± 0.77 log CFU/mL for Dithiothreitol, 10.0 ± 0.75 for sonication and 10.1 ±0.73 for dithiothreitol + sonication. No statistical differences between the 3 treatments were evidenced by ANOVA analysis. Conclusions. Results seems to confirm that treatment with dithiothreitol is equivalent to sonication in recovering bacteria from biofilm grown on inert surface. Combining dithiotreitol treatment with sonication does not significantly improve bacterial recovery in respect to each treatment alone

Wear and corrosion debris generated from total hip replacements (THR) can cause adverse local tissue reactions (ALTR) or osteolysis, often leading to premature implant failure. The tissue response can be best characterized by histopathological analysis, which accurately determines the presence of cell types, but is limited in the characterization of biochemical changes (e.g. protein conformation alteration). Fourier transform infrared micro-spectroscopy imaging (FTIRI) enables rapid analysis of the chemical structure of biological tissue with a high spatial resolution, and minimal additional sample preparation. The data provides the most information through multivariate method carried out by hierarchical clustering analysis (HCA). It is the goal of this study to demonstrate the beneficial use of this multivariate approach in providing pathologist with biochemical information from cellular and subcellular organization within joint capsule tissue retrieved from THR patients. Joint capsule tissue from 2 retrieved THRs was studied. Case 1: a metal-on-polyethylene THR, and Case 2: a dual modular metal-on-metal THR. Prior to FTIRI analysis, tissue samples were formalin-fixed paraffin-embedded and 5μm thick microtome sectioned samples were prepared and mounted on BaF. 2. discs and deparaffinized. FTIRI data were collected using high-definition transmission mode (pixel size: ∼1.1 μm. 2. ). Hyperspectral images were exported to CytoSpec V2.0.06 for processing and reconstruction into pseudo-color maps based on cluster assignments. Case 1 exhibited a strong presence of lymphocytes and macrophages (Fig. 1a). Since the process of taking second derivatives reduces the half width of the spectral peaks, it increases the sensitivity toward detecting shoulders or second peaks that may not be apparent in the raw spectra (Fig. 1b). Thus, areas occupied by lymphocytes and macrophages can be easily distinguished providing a fast tissue screening method. Here, HCA was able to distinguish macrophages and lymphocytes based on the infrared response, even in areas where both occurred intermixed. (Fig. 1c) The tissue in direct proximity to cells had a slightly altered collagenous structure. Case 1 also exhibited multiple glassy, green particles which can typically observed around THRs that underwent taper corrosion (Fig. 2a). HCA image was able to visualize and distinguish large CrPO. 4. particles, embedded within fibrin exudate rich areas, collagenous tissue without inflammatory cells, and a nearby area with a strong macrophage presence and some finer CrPO. 4. particles (Fig. 2d). Moreover, this method can not only locate macrophages, but distinguish particle-laden macrophages depending the type of particles within the cells. In Case 2 (Fig. 3a), clustering results (Fig. 3 b&c) are consistent with the fact that different particle types are associated with MoM bearing surface wear (Co rich particles), corrosion of the CoCrMo taper junctions (Cr-oxides and –phosphate), fretting of Ti-alloy dual modular tapers (Ti-oxides, Ti alloy particles), and even suture debris, which all occurred in this case. Although details of debris types are not available, specifications are possible by coupling other techniques. The results demonstrate that multivariate FTIRI based spectral histopathology is a powerful tool to characterize the chemical structure and foreign body response within periprosthetic tissue, thus providing insights into the biological impact of different types of implant debris. For any figures or tables, please contact the authors directly

Background. Systemically administered vancomycin may provide insufficient target-site concentrations. Intraosseous vancomycin administration has the potential to overcome this concern by providing high target-site concentrations. Aim. To evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model. Method. Eight female pigs were assigned to receive 500 mg diluted vancomycin (50 mg/mL) through an intraosseous cannula into the proximal tibial cancellous bone. Microdialysis was applied for sampling of vancomycin concentrations in tibial cancellous bone adjacent to the intraosseous cannula, in cortical bone, in the intramedullary canal of the diaphysis, in the synovial fluid of the knee joint, and in the subcutaneous tissue. Plasma samples were obtained. Samples were collected for 12 hours. Results. High vancomycin concentrations were found in the tibial cancellous bone with a mean peak drug concentration of 1,236 (range 28–5,295) µg/mL, which remained high throughout the sampling period with a mean end concentration of 278 (range 2.7–1,362.7) µg/mL after 690 min. The mean (standard derivation (SD)) peak drug concentration in plasma was 19 (2) µg/mL, which was obtained immediately after administration. For the intramedullary canal, in the synovial fluid of the knee joint, and subcutaneous tissue, comparable mean peak drug concentration and mean time to peak drug concentration were found in the range of 7.5–8.2 µg/mL and 45–70 min, respectively. Conclusions. Tibial intraosseous administration of vancomycin provided high mean concentrations in tibial cancellous bone throughout a 12-hour period, but with an immediate and high systemic absorption. The concentrations in cancellous bone had an unpredictable and wide range of peak concentration. Low mean concentrations were found in all the remaining compartments. Our findings suggest that intraosseous vancomycin administration in proximal tibial cancellous bone only is relevant as treatment in cases requiring high local concentrations nearby the intraosseous cannula

Aims

Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation.

Aim. Low-grade infections cannot be easily distinguished from aseptic complications frequently leading to false negative diagnoses and late onset of anti-bacterial therapy. Therefore, there is a great need to establish biomarkers for early detection of low-grade infections. Method. In this study, we focused on the investigation of anti-α-defensin, anti-C3, anti-C5 and anti-C9 as potential biomarkers for infection in a cohort of hip and knee septic revision cases, taking patient characteristics and comorbidities into account. Here we included 78 patients with septic (35) and aseptic (43) (woman:37, men:42, age 50 – 93 years) revision surgeries of hip and knee. CRP serum levels and leucocyte blood values were evaluated. Patient characteristics, including age, number of prior revision surgeries and comorbidities were recorded. Periprosthetic tissue was stained histologically with Hematoxylin/Eosin and immunohistologically with different antibodies. Results. The CRP values were significantly increased in the septic cohort, but no changes were observed in leucocyte count. Interestingly, we found a strong increase in the terminal complement system component C9 (septic: 0.1% ± 0.2% aseptic: 0.01% ± 0.05%, p= 0.0004) in the septic periprosthetic tissue. The predictive value of α-defensin staining was not statistically significant (septic: 0.5% ± 0.7% aseptic: 0.1% ± 0.6%, p= 0.09). Analyzing the synovial fluid of aseptic and septic patients, the presence of C9 in the septic group (1.8 ± 0.4) was not significantly higher compared to the aseptic (1.9 ± 0.7) group. The next step was to investigate the specificity C9 detection using different joint related diseases such as chondrocalcinosis (CC), rheumatoid arthritis (RA) and metallosis. The median of C9 staining in the CC group (0 ± 0.0001) was significant lower than the infection group. Similar results have been observed in RA (0.0003 ± 0.2) and the metallosis group (0.0002 ± 0.01). Conclusions. We found a strong predictive value of anti-C9 staining for tissue infection, suggesting that C9 deposition could be a novel biomarker for the identification of periprosthetic joint infections using tissue biopsies

This in-vitro study finds which hip joint soft tissues act as primary and secondary passive internal and external rotation restraints so that informed decisions can be made about which soft tissues should be preserved or repaired during hip surgery. The capsular ligaments provide primary hip rotation restraint through a complete hip range of motion protecting the labrum from impingement. The labrum and ligamentum teres only provided secondary stability in a limited number of positions. Within the capsule, the iliofemoral lateral arm and ischiofemoral ligaments were primary restraints in two-thirds of the positions tested and so preservation/repair of these tissues should be a priority to prevent excessive hip rotation and subsequent impingement/instability for both the native hip and after hip arthroplasty

Introduction. Osteoarthritis (OA), a painful, debilitating joint disease, often caused by excessive joint stress, is a leading cause of disability (World Health Organisation, 2003) and increases with age and obesity. A 5° varus malalignment increases loading in the medial knee compartment from 70% to 90% (Tetsworth and Paley, 1994). Internal unloading implants, placed subcutaneously upon the medial aspect of the knee joint, are designed to offload the medial compartment of the knee without violating natural joint tissues. The aim of this study is to investigate the effect of an unloading implant, such as the Atlas™ knee system, on stress within the tibiofemoral joint with different grades of cartilage defects. Methods. To simulate surgical treatment of medial knee OA, a three-dimensional computer-aided design of an Atlas™ knee system was virtually fixed to the medial aspect of a validated finite element knee model (Mootanah, 2014), using CATIA v5 software (Dassault Systèmes, Velizy Villacoublay, France). The construct was meshed and assigned material properties and boundary conditions, using Abaqus finite element software (Dassault Systèmes, Velizy Villacoublay, France). A cartilage defect was simulated by removing elements corresponding to 4.7 mm. 2. The international cartilage repair society (ICRS) Grade II and III damage were simulated by normalized defect depth of 33% and 67%, respectively. The femur was mechanically grounded and the tibia was subjected to loading conditions corresponding to the stance phase of walking of a healthy 50-year-old 68-Kg male with anthropometrics that matched those of the cadaver. Finite element analyses were run for peak shear and von Mises stress in the medial and lateral tibiofemoral compartments. Results. Von Mises stress distribution in the tibial cartilage, with ICRS Grade II and III defects, without the unloading implant, at the end of weight acceptance (15% of the gait cycle) were analysed. The internal unloading implant reduces peak von Mises stress by 40% and 43% for Grade II and Grade III cartilage defects, respectively. The corresponding reductions in shear stress are 36% and 40%. Consistent reduction in peak von Mises stress values in the medial cartilage-cartilage and cartilage-meniscus contact areas were predicted throughout the stance phase of the gait cycle for ICRS Grade II defect. Similar results were obtained for Grade III defect and for peak shear stress values. There were no overall increases in peak von Mises stress values in the lateral tibial cartilage. Discussion and Conclusions. The internal unloading implant is capable of reducing von Mises and shear stress values in the medial tibial cartilage with ICRS Grade II and III defects at the cartilage-cartilage and cartilage-meniscus interfaces throughout the stance phase of the gait cycle. This did not result in increased stress values in the lateral tibial cartilage. Our model did not account for the viscoelastic effects of the cartilage and meniscus. Results of this study are based on only one knee specimen. The internal unloading implant may protect the cartilage in individuals with medial knee osteoarthritis, thereby delaying the need for knee replacements

Periprosthetic joint infection (PJI) is one of the most feared complications following total knee arthroplasty (TKA). Despite improved peri-operative antibiotic management and local antibiotic-loaded bone cement PJI is reported in about 0.5–1.9 % of primary knee replacement. In case of revision knee arthroplasty the infection rate even occurs at about 8–10 %. Depending on an acute or late PJI several surgical methods are used to treat the infection. However, suffering of a late PJI, the only surgical procedure remains the exchange of the TKA in combination with a radical debridement and removal of all foreign material. In order to achieve complete debridement of the joint, the soft tissue must be radically excised. Frequently, the debridement of the posterior capsule causes severe difficulties, therefore it might be necessary to resect the collateral ligaments to be able to reach the posterior parts of the capsule. But this necessitates the use of a higher level of constraint such as a rotating or total hinge and fully cemented long stemmed revision implants. Furthermore, due to the cemented stems, a sufficient amount of antibiotic-loaded cement may be delivered to the bone as topical therapy. Up to now, several studies have shown excellent functional long-term results for hinge knee prostheses after PJI and a very good infection control rate. Advantages of the hinge knee prosthesis in cases of PJI are the opportunity for a complete debridement especially while addressing the posterior capsule after resection of the collateral ligaments and for delivering antibiotic-loaded bone cement at the stems of the prosthesis for topic therapy. Disadvantages are the need for a higher level of constraint and a possible higher blood loss due to the radical debridement

To evaluate the proportion of microbial associations causing PJI, diversity of their strains and impact on treatment failure after the removal of the hip implant and insertion of a spacer. Spectrum of pathogens in 189 cases of PJI was studied retrospectively. Strains were isolated from the joint aspirates, tissue samples and removed orthopedic devices. The cohort comprised 144 cases of PJI after primary THA and 45 cases after the hip replacement revision surgery. All patients underwent first stage of two-stage revision procedure which involves the removal of a hip implant, debridement of infected periprosthetic tissues and subsequent insertion of a bone cement spacer. There were 92 males and 97 females (median age of 57 yrs). Statistical analysis of the results was performed with GraphPad Prism 6.0 (California, USA). Microbial associations were detected in 28.6% (n=54) of PJI cases. Gram-positive bacteria prevailed in both groups with mono- and polymicrobial etiology. There were 52.5% of S. aureus isolates in monomicrobial group and 25% isolates in polymicrobial group (p=0.0002). This also included 8.4 and 20.6% isolates of MRSA, respectively (p<0.0001). CNS were detected in 20.1% of mono- and 27.9% of polymicrobial infection isolates, including about 40% of MRSE in both groups. Gram-negative pathogens accounted for 25.7% of isolates in polymicrobial group and 14.1% in monomicrobial group (p=0.022). Non-fermenting bacteria prevailed among Gram-negative strains presented in associations. Acinetobacter sp. and P. aeruginosa were identified in 7.4% (p=0.043) and 5.1% (p=0.56) of polymicrobial isolates. The percentage of treatment failure after the removal of the hip implant and insertion of a spacer was considerably higher (p<0.0001) in patients with polymicrobial than monomicrobial infection: 72.2 vs 25.2%, respectively. The proportion of isolates in microbial associations involving Gram-negative pathogens was 61.5% in patients with infection recurrence and 26.7% in patients with a successful outcome of the surgery (p=0.033). Microbial associations were found in 28.6% of PJI cases after hip arthroplasty. They posed a significant risk for treatment failure after removal of the hip implant and insertion of a spacer. The multidrug-resistant strains (MRSA, Acinetobacter sp. and P. aeruginosa) were often isolated in microbial associations. Our results suggest that further study of the risk factors for polymicrobial infection is necessary in patients with PJI. Identification of a patient group at high risk for developing polymicrobial PJI will allow prescription of empiric antimicrobial therapy in time, taking into account possible multi-resistant pathogens

Expectations for ceramic-on-metal (COM) bearings included (i) optimal lubrication due to smoother ceramic heads (ii), reduction of metal ions due to elimination of CoCr heads, and (iii) ‘differential hardness’ reducing adhesive wear and squeaking (Firkins 2001, Williams 2007). Additional benefits included (iv) use of heads larger than for ceramic-on-ceramic (COC), (v) reduction in taper corrosion and (vi) simulator studies clearly demonstrated metal ions and wear both reduced compared to MOM (Firkins 2001, Williams 2007, Ishida 2007). However, contemporary ‘3rd body wear’ paradigms focused only on metal debris size range 0.025–0.035um (Firkins 2001). Thus, neglected was the effect of hip impingement, provoking release of large metal particles sized 20–200um (Clarke 2013). In this study, we compared COM retrievals using hypotheses that adverse COM cases would demonstrate a combination of (a) steeply inclined cups, (b) liner “edge-loading”, (c) Ti6Al4V contamination on ceramic, and (d) evidence of 3rd-body CoCr wear by large particles. As a case example, this 51-year old female had her metal-polyethylene (MPE) bearing revised to COM in June 2011. She reported no symptoms 1-year post-op, but scans revealed a palpable mass in the inguinal region of left hip. By March 2013 the patient reported mild pain in her hip, which progressed to severe by April 2014. Scans showed a solid and cystic iliopsoas bursitis while cup position had changed from 43o to 73o inclination. Revision was performed in June 2014, her joint tissues were found extensively stained due to metal contamination, and histology described formation of a large pseudotumor. Analysis of retrieved components was by interferometry, SEM and EDS. Detailed maps were made of wear areas in heads and cups and volumetric wear was determined by CMM techniques. This adverse COM example revealed large diametral mismatch (595um) compared to COM controls (75–115um). The ceramic head had a broad polar stripe of CoCr contamination, roughness 0.1–0.3um high. Equatorial ceramic areas showed arrays of thin metal smears that demonstrated elemental Ti and Al. The CoCr liner revealed wear area into cup rim, as “edge loading”, and also featured a focal rim-defect over 18o circumferential arc. Liner scratches were 20um wide and larger, and wear-rate of CoCr liner averaged approximately 50mm3 per year. In contrast, ceramic head had minimal wear. Our study highlights the underappreciated risk of impingement by metallic prosthetic components. Prior studies of ceramic heads showed black metallic smears. With COM we can anticipate that the broad polar smear will be CoCr alloy (wear of liner on head). However, Ti6Al4V smearing on ceramic heads is a notable signpost indicating impingement by the Ti6Al4V acetabular shell. The femoral neck (Ti6Al4V: CoCr), may also be damaged. Release of large metal particles, 1500-times larger than prior predictions, provoke a particularly adverse ‘3rd body wear’ (Halim, 2015). Such cases confirm our four hypotheses, that COM bearings will then fail in a way similar to MOM. In contrast, COC bearings are immune to such impingement and 3rd-body metal damage

Introduction. About 2% of primary total joint replacement arthroplasty (TJA) procedures become infected. Periprosthetic joint infection (PJI) is currently one of the main reasons requiring costly TJA revisions, posing a burden on patients, physicians and insurance companies. 1. Currently used drug-eluting polymers such as bone cements offer limited drug release profiles, sometimes unable to completely clear out bacterial microorganisms within the joint space. For this study we determined the safety and efficacy of an antibiotic-eluting UHMWPE articular surface that delivered local antibiotics at optimal concentrations to treat PJI in a rabbit model. Materials and Methods. Skeletally mature adult male New Zealand White rabbits received either two non-antibiotic eluting UHMWPE (CONTROL, n=5) or vancomycin-eluting UHMWPE (TEST, n=5) (3 mm in diameter and 6 mm length) in the patellofemoral groove (Fig. 1). All rabbits received a beaded titanium rod in the tibial canal (4 mm diameter and 12 mm length). Both groups received two doses of 5 × 10. 7. cfu of bioluminescent S. aureus (Xen 29, PerkinElmer 119240) in 50 µL 0.9 % saline in the following sites: (1) distal tibial canal prior to insertion of the rod; (2) articular space after closure of the joint capsule (Fig. 1). None of the animals received any intravenous antibiotics for this study. Bioluminescence signal (photons/second) was measured when the rabbits expired, or at the study endpoint (day 21). The metal rods were stained with BacLight. ®. Bacterial Live-Dead Stain and imaged using two-photon microscopy to detect live bacteria. Hardware, polyethylene implants and joint tissues were sonicated to further quantify live bacteria via plate seeding. Results. All control rabbits expired within 7 days (Fig. 2a). One rabbit in the test group expired at day 7 and another at day 15. All control rabbits had positive bioluminescence (live bacteria), while none of the test rabbits did (Fig 2b). Kidney (creatinine and BUN) and liver functions (ALT and ALP) remained normal for all rabbits. All control rabbits showed positive bacterial culture after sonication, while all test rabbits were negative. Two-photon imaging showed 75±10 % viability for bacteria adhered to the metal rods in the control and no viability in the test group. Discussion. This rabbit model showed that vancomycin eluted from UHMWPE is sufficient to eradicate S. aureus in joint space and in between the bone-implant interface of tibial canal. One limitation of this study is the lack of intravenous antibiotic treatment, which is standard clinical practice. In addition, joint infections are often associated with already formed biofilms, which were not tested in this study. However, safety data (normal kidney and liver functions) and complete eradication of S. aureus is an encouraging finding. Conclusion. Vancomycin-eluting UHMWPE effectively eliminated bacteria in a rabbit model of acute peri-prosthetic joint infection. This material is promising as a replacement liner to treat joint infections in revision surgery. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Unicompartmental knee replacements offer improved function with more rapid recovery compared to TKR. There is no published experience with introducing this procedure as a day case in the UK. We report on our experience with a new protocol allowing the patient to be discharged on the day of surgery. A new combination of anaesthetic and surgical techniques are employed. Paracetamol, ibuprofen and pregabalin are given pre-operatively. Patients receive a GA and a subsartorial saphenous nerve block is administered under ultrasound control. The surgery is performed using a routine minimally invasive technique. The joint and surrounding tissues are infiltrated with a combination of LA and adrenaline. Wound closure is with subcutaeneous suture and tissue glue. Patients are mobilised on the day of surgery and if comfortable discharged on paracetamol, codeine, ibuprofen, tramadol P.R.N and buprenorphine patch. Length of stay, pain scores, presence of nausea/vomiting, dizziness, drowsiness, post-operative bleeding and patient satisfaction are all recorded. 18 out of 19 patients have been discharged on the day of surgery. All record high satisfaction. Patients can be safely discharged on the day of surgery after UKR with high levels of satisfaction. We believe we are the first unit in the UK to achieve this

INTRODUCTION:. To avoid the early onset of osteoarthritis after partial meniscectomy an effective replacement of injured meniscal tissue would be desirable. The present study investigates the behaviour of a new silk derived scaffold supplied by Orthox Ltd. (Abingdon, UK) in an in vivo sheep model. METHODS:. The scaffolds where derived from silk fibres by processing into an open porous matrix. Nine sheep (4 ± 1 years) underwent partial meniscectomy at the anterior horn of the medial meniscus followed by implantation of a scaffold. The unoperated contralateral stifle joint served as control. After six months the animals were sacrificed and the joints inspected for inflammation. The Young's modulus of the tibial cartilage, meniscus and scaffold was determined by indentation or confined compression tests. All tissues were fixed in formaldehyde for histology. The data were analysed by a Wilcoxon and Mann-Whitney-U-test. RESULTS:. The sheep were free of lameness 4 days p.o. The macroscopic analysis of the genual region and of the synovial membrane showed no signs of inflammation. This was confirmed by histological sections of synovial membrane, meniscus and scaffold. In histology, amorphous material, some fibroblast-like cell clusters and connective tissue formation was visible inside the pores of the scaffold. There were no statistically significant differences between the Young's moduli of the three measuring points in the operated and unoperated stifle joints. The meniscal tissue showed a higher modulus than the scaffolds. The scaffold's modulus significantly increased after three months implantation. DISCUSSION & CONCLUSIONS:. The presented silk scaffold withstood the loads occurring during the six months implantation period. It showed promising properties concerning biocompatibility and cartilage protection and its mechanical properties started to approach those of meniscal tissue

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities.

Cite this article: Bone Joint Res 2015;4:105–116

Bactericidal levels of antibiotics are difficult to achieve in infected total joint arthroplasty when intravenous antibiotics or antibiotic-loaded cement spacers are used, but intra-articular (IA) delivery of antibiotics has been effective in several studies. This paper describes a protocol for IA delivery of antibiotics in infected knee arthroplasty, and summarises the results of a pharmacokinetic study and two clinical follow-up studies of especially difficult groups: methicillin-resistant Staphylococcus aureus and failed two-stage revision. In the pharmacokinetic study, the mean synovial vancomycin peak level was 9242 (3956 to 32 150; sd 7608 μg/mL) among the 11 patients studied. Serum trough level ranged from 4.2 to 25.2 μg/mL (mean, 12.3 μg/mL; average of 9.6% of the joint trough value), which exceeded minimal inhibitory concentration. The success rate exceeded 95% in the two clinical groups. IA delivery of antibiotics is shown to be safe and effective, and is now the first option for treatment of infected total joint arthroplasty in our institution.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):31–6.