The course of secondary fracture healing typically consists of four major phases including inflammation, soft and hard callus formation, and bone remodeling. Callus formation is promoted by mechanical stimulation, yet little is known about the healing tissue response to strain stimuli over shorter timeframes on hourly and daily basis. The aim of this study was to explore the hourly, daily and weekly variations in bone healing progression and to analyze the short-term response of the repair tissue to well-controlled mechanical stimulation. A system for continuous monitoring of fracture healing was designed for implantation in sheep tibia. The experimental model was adapted from Tufekci et al. 2018 and consisted of 3 mm transverse osteotomy and 30 mm bone defect resulting in an intermediate mobile bone fragment in the tibial shaft. Whereas the distal and proximal parts of the tibia were fixed with external fixator, the mobile fragment was connected to the proximal part via a second, active fixator. A linear actuator embedded in the active fixator moved the mobile fragment axially, thus stimulating mechanically the tissue in the osteotomy gap via well-controlled displacement being independent from the sheep's functional weightbearing. A load sensor was integrated in the active fixation to measure the force acting in the osteotomy gap. During each stimulation cycle the displacement and force magnitudes were recorded to determine in vivo fracture stiffness. Following approval of the local ethics committee, experiments were conducted on four skeletally mature sheep. Starting from the first day after surgery, the daily stimulation protocols consisted of 1000 loading events equally distributed over 12 hours from 9:00 to 21:00 resulting in a single loading event every 44 seconds. No stimulation was performed overnight. One animal had to be excluded due to inconsistencies in the load sensor data. The onset of tissue stiffening was detected around the eleventh day post-op. However, on a daily basis, the stiffness was not steadily increasing, but instead, an abrupt drop was observed in the beginning of the daily stimulations. Following this initial drop, the stiffness increased until the last stimulation cycle of the day. The continuous measurements enabled resolving the tissue response to strain stimuli over hours and days. The presented data contributes to the understanding of the influence of patient activity on daily variations in tissue stiffness and can serve to optimize rehabilitation protocols post fractures

Mesenchymal stem cells (MSCs) have the potential to repair and regenerate damaged tissues in response to injury, such as fracture or other tissue injury. Bone marrow and adipose tissue are the major sources of MSCs. Previous studies suggested that the regenerative activity of stem cells can be enhanced by exposure to tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells-derived mesenchymal-like progenitors (hiPSCs-MPs) can enhance the regenerative potential of human bone marrow mesenchymal stromal cells (hBMSCs). ECM was engineered from hiPSC-MPs. ECM structure and composition were characterized before and after decellularization using immunofluorescence and biochemical assays. hBMSCs were cultured on the engineered ECM, and differentiated into osteogenic, chondrogenic and adipogenic lineages. Growth and differentiation responses were compared to tissue culture plastic controls. Decellularization of ECM resulted in efficient cell elimination, as observed in our previous studies. Cultivation hBMSCs on the ECM in osteogenic medium significantly increased hBMSC growth, collagen deposition and alkaline phosphatase activity. Furthermore, expression of osteogenic genes and matrix mineralization were significantly higher compared to plastic controls. Chondrogenic micromass culture on the ECM significantly increased cell growth and expression of chondrogenic markers, including glycosaminoglycans and collagen type II. Adipogenic differentiation of hBMSCs on the ECM resulted in significantly increased hBMSC growth, but significantly reduced lipid vacuole deposition compared to plastic controls. Together, our studies suggest that BMSCs differentiation into osteogenic and chondrogenic lineages can be enhanced, whereas adipogenic activity is decreased by the culture on engineered ECM. Contribution of specific matrix components and underlying mechanisms need to be further elucidated. Our studies suggest that the three-lineage differentiation of aged BMSCs can be modulated by culture on hiPSC-engineered ECM. Further studies are aimed at scaling-up to three-dimensional ECM constructs for osteochondral tissue regeneration

Introduction. We studied free (= local powder) tobramycin and doxycycline, and controlled release (= local lipid bilayer) doxycycline formulations in a rat model representing a generic joint infection. We . hypothesized. that evidence of infection (quantitative colony forming units (CFU), qualitative SEM, histopathology) (1a) would be reduced with local vs. systemic antibiotic, (1b) any antibiotic would be superior to control (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4-week euthanasia. Methods. Study groups. included infected and non-infected (1) control, (2) systemic ceftriaxone (daily), (3) local tobramycin, (4) local doxycycline and (5) controlled release doxycycline. With IACUC approval, (10 rats/group; power =0.8), 50-μl, 10×4 CFU Staphylococcus aureus, slowly injecting into distal femoral medullary canal, reliably created joint infection. Antibiotic formulation was introduced locally into cavity and joint, pin was inserted, and tissues closed. After 4-weeks, serum, pin, bone and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on surface of pin, histopathology identified tissue response, liquid chromatography/mass spectrometry measured plasma antibiotic. Kruskal-Wallis one-way ANOVA compared groups. Results. Groups receiving antibiotic reported lower CFU/ml in synovium compared with control (no treatment) group (1b), but there was no difference between systemic, free or controlled antibiotics (1a). Different results with different antibiotics were shown, with free tobramycin reducing CFU/ml to a greater extent than free doxycycline in the synovium (2) (p<0.05). Antibiotic in plasma was nondetectable all groups (3). SEM revealed some biofilm on pin in all groups. . Limitations. include inoculation method, single observation period, administration of only one bacterial and antibiotic dose, and not including pairing local and systemic antibiotic. Conclusion. There was no difference in infection reduction nor detectable antibiotic in serum for any antibiotic formulation, but CFU's in synovium differed based on antibiotic formulation. For any tables or figures, please contact the authors directly

Introduction. The combined incidence of anatomic (aTSA) and reverse total shoulder arthroplasties (rTSA) in the US is 90,000 per annum and rising. There has been little attention given to potential long-term complications due to periprosthetic tissue reactions to implant debris. The shoulder has been felt to be relatively immune to these complications due to lower acting loads compared to other joint arthroplasties. In this study, retrieved aTSAs and rTSAs were examined to determine the extent of implant damage and to characterize the nature of the corresponding periprosthetic tissue responses. Methods. TSA components and periprosthetic tissues were retrieved from 23 (eleven aTSA, twelve rTSA). Damage to the implants was characterized using light microscopy. Head/stem taper junction damage was graded 1–4 as minimal, mild, moderate or marked. Damage on polyethylene (PE) and metal bearing surfaces was graded 1–3 (mild, moderate, marked). H&E stained sections of periprosthetic soft tissues were evaluated for the extent and type of cellular response. A semi-quantitative system was used to score (1=rare to 4=marked) the overall number of particle-laden macrophages, foreign body giant cells, lymphocytes, plasma cells, eosinophils, and neutrophils. Implant damage and histopathological patterns were compared between the two TSA groups using the Mann-Whitney and Spearman tests. Results. The PE bearing surfaces of aTSAs were dominated by three-body wear and plastic deformation, whereas the rTSA PE components exhibited mainly polishing and scratching. Metal surface damage occurred in a few cases of both groups. Only one aTSA case exhibited marked taper corrosion. In both groups the primary nature of the inflammatory response was a moderate to marked macrophage response to wear particles (78% of cases). The particle-laden macrophages tended to occur in broad sheets and contained metal, PE, bone cement and suture debris. The extent of macrophage and foreign body giant cell responses was greater in the aTSA group (p≤0.001). Metal particles were seen in 63% of aTSAs and 83% of rTSAs. In the aTSA group, bone cement was seen in all cases and suture was observed in 9 cases, and their presence was larger compared to the rTSA group (p≤0.022). There was no difference in the number of other cell types between the groups. A mild lymphocyte response and chromium-phosphate debris was present within the tissue of the aTSA case with marked corrosion, which may be indicative of an early stage adverse local tissue reaction (ALTR) analog to total hip replacements with taper corrosion. Conclusion. Both groups exhibited a strong macrophage response to a combination of different types of implant debris—PE, metal, bone cement and suture. The prevalence of a marked macrophage response was larger in the aTSA group which may be explained by the larger overall presence of cement and suture within this group. PE particles may differ in size between groups due to different acting wear mechanisms which may also affect the extent of the macrophage response. Although corrosion within modular junctions was overall rare, the presence of one case with marked corrosion shows that taper corrosion and subsequent ALTRs are possible in TSAs. For any figures or tables, please contact authors directly

Objectives. Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. Methods. ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. Results. Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. Conclusion. The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of β-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices. Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266–274. DOI: 10.1302/2046-3758.86.BJR-2018-0224.R2

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

Aims

The aims of the study were to report for a cohort aged younger than 40 years: 1) indications for HRA; 2) patient-reported outcomes in terms of the modified Harris Hip Score (HHS); 3) dislocation rate; and 4) revision rate.

Aims

Taper corrosion has been widely reported to be problematic for modular total hip arthroplasty implants. A simple and systematic method to evaluate taper damage with sufficient resolution is needed. We introduce a semiquantitative grading system for modular femoral tapers to characterize taper corrosion damage.

Aims

Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Introduction. Little is known about the relationship between head-neck corrosion and its effect on periprosthetic tissues and distant organs in the majority of patients hosting apparently well-functioning devices. We studied the degree and type of taper damage and the histopathologic response in periprosthetic tissue and distant organs. Methods. A total of 50 contemporary THRs (34 primary, 16 revision) retrieved postmortem from 40 patients after 0.4–26 years were studied. Forty-three femoral stems were CoCrMo and 7 were Ti6Al4V. In every case, a CoCrMo-alloy head articulated against a cementless polyethylene cup (19 XLPE and 31 UHMWPE). H&E and IHC sections of the joint pseudocapsules and liver were graded 1–4 for the intensity of various inflammatory cell infiltrates and tissue necrosis. The nature of the tissue response in the joint capsule, liver, spleen, kidneys and lymph nodes was assessed. Wear and corrosion products in the tissues were identified using SEM and EDS. Taper surfaces were graded for corrosion damage using modified Goldberg scoring and examined by SEM to determine the acting corrosion mode. Correlations between damage scores and the histologic variables were generated using the Spearman test. Results. No correlation was seen between taper damage scores and the macrophage response in the joint pseudocapsule. The distribution of corrosion scores for heads and femoral trunnions is shown in Figure 1. Moderate or severe corrosion of the head and/or trunnion was present in 9 hips (8 CoCr/CoCr and 1 CoCr/TiAlV). One patient with bilateral hips had local ALVAL-like lymphocyte-dominated tissue reactions (Figure 2) and mild focal lymphocytic infiltrates in the liver and kidneys (Figure 3). This was associated with severe intergranular corrosion of the CoCrMo trunnion and column damage on the head taper. Particle-laden macrophages in pseudocapsules were significantly correlated with liver macrophages (r=.382, p=0.012) and liver lymphocytes (r=.367, p=0.013). Pseudocapsule macrophage responses to metallic and/or polyethylene wear particles ranged widely from minimal to marked. Focal tissue necrosis was related to high concentrations of particulate wear debris. A minimal number of metallic particle-laden macrophages were also detected in the liver and spleen; and macrophage granulomas were present in para-aortic lymph nodes, especially in revision cases. DISCUSSION. The generation of metal ions and particulates at corroded CoCrMo heads and CoCrMo or Ti6Al4V trunnions was a significant contributor to the presence of perivascular lymphocytes within the joint pseudocapsule, with 1 patient showing a histologic pattern consistent with ALVAL. Patient factors and the rate of corrosion are among variables influencing whether an ALVAL-type reaction will develop and whether or not it will become symptomatic. Macrophages in the joint pseudocapsules were positively correlated with inflammatory cells in the liver. In this study, the intensity of inflammatory infiltrates in distant organs was mild. However, several cases of organ dysfunction have been reported in association with catastrophic wear of CoCrMo components. It continues to be essential to minimize the generation of metal ions and particulates and to improve strategies for identifying and managing patients exposed to high levels of degradation products. For any figures or tables, please contact the authors directly

Aims

Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

A challenging problem in ultrasound based orthopaedic surgery is the identification and interpretation of bone surfaces. Recently we have proposed a new fully automatic ultrasound bone surface enhancement filter in the context of spine interventions. The method is based on the use of a Gradient Energy Tensor filter to construct a new feature enhancement metric, which we call the Local Phase Tensor. The goal of this study is to provide further improvements to the proposed filtering method by incorporating a-priori knowledge about the physics of ultrasound imaging and salient grouping of enhanced bone features. Typical ultrasound scan of the spine, there is a large soft tissue interface present close to the transducer surface with high intensity values similar to those of the bone anatomy response. Typical ultrasound image segmentation or enhancement methods will be affected by this thick soft tissue response. In order to weaken this soft tissue interface we calculate a new transmission map where features deeper in the ultrasound image have higher transmission values and shallow features have lower transmission values. The calculation of this new US transmission/attenuation map allows the proposed image enhancement method to mask out erroneous regions, such as the soft tissue interface, and improve the accuracy and robustness of the spine surface enhancement. The masked US images were used as an input to the LPT image enhancement method. In order to provide a more compact spine surface representation and further reduce the typical US imaging artifacts and soft tissue interfaces we calculate saliency Local Phase Tensor features. The saliency images are computed using Difference of Gaussian filters. Qualitative results, obtained from in vivo clinical scans, show a strong correspondence between enhanced features and the actual bone surfaces present in the ultrasound scans. Future work will include the extension of the proposed method to 3D and validation of the method in the context of intra-operative ultrasound image registration in CAOS applications

Introduction. Recent advances in nano-surface modification technologies are improving osseointegration response between implant materials and surrounding tissue. Living cells have been shown to sense and respond to cues on the nanoscale which in turn direct stem cell differentiation. One commercially practical surface treatment technique of particular promise is the modification of titanium implant surfaces via electrochemical anodization to form arrays of vertically aligned, laterally spaced titanium oxide (TiO2) nanotubes on areas of implants where enhanced implant–to-bone fixation is desired. Foundational work has demonstrated that the TiO2 nanotube surface architecture significantly accelerates osteoblast cell growth, improves bone-forming functionality, and even directs mesenchymal stem cell fate. The initial in vitro osteoblast cell response to such TiO2 nanotube surface treatments and corresponding in vivo rabbit tissue response are evaluated. Methods. Arrays of 30, 50, 70, 100nm diameter TiO2 nanotubes formed onto titanium surfaces were compared to grit blasted titanium controls in vitro (Figure 1). SEM micrographs of bovine cartilage chondrocytes (BCCs) on the nanotube surfaces were evaluated after 2 hours, 24 hours, and 5 days of culture. Additionally 20 samples each of various nanotube diameters and the non-nanotube treated titanium controls were evaluated after exposure to human mesenchymal stem cell (hMSC) after 2 hours and 24 hours. The left tibia and right tibia of four rabbits were implanted with disk shaped titanium implants (5.0 mm dia. × 1.5 mm) with and without TiO2 nanotubes. The front side of each implant faced the rabbit tibia bone and the back side of the implant had screw holes for post-in vivo tensile testing. After 4 weeks, the bones with implants were retrieved for mechanical testing and histology analysis. Comparative osteogenic behavior on metal oxide nanotube surfaces applied to other implant material surface chemistries including ZrO2, Ta, and Ta2O5 were also evaluated along with TiO2 nanotubes formed on a thin films of titanium on the surface of zirconia and CoCr alloy orthopedic implants. Results. A striking difference in ECM fibril formation and cell clustering on the nanotube substrates is evident in larger diameter nanotubes compared to non-treated titanium as shown by the arrows in Figure 2. The average fracture strength was significantly higher for TiO2 nanotube implants (10.8 N) compared to the grit blasted titanium control implants (1.2 N). The histology at week 4 shown in Figure 3 confirms direct bonded growth of new bone onto the nanotubes with a significantly less trapped amorphous tissue at the implant-bone interface compared to the control. Conclusions. The TiO2 nanotubes significantly enhanced the adhesion and growth of osteoblast cells (in vitro) by 300 to 400% as compared to non-nanostructure surfaces. In vivo implant tests indicate enhanced osseointegration of new bone cells on the TiO2 nanotube implant surface, with a 600% improvement in adhesion strength compared to conventional sand-blasted titanium surfaces. Discussion. Both in vitro and in vivo analysis indicates that TiO2 nanotubes enhance the speed and proliferation of osseointegration. This surface treatment technique can be applied to non-porous or porous surfaces on implants where optimized bone fixation is desired

The suture properties associated with a successful tendon repair are: high tensile strength, little tissue response, good handling characteristics and minimal plastic deformation. Plastic deformation contributes to gap formation at a tendon repair site. Gaps greater than 4mm are prone to failing. This study investigates whether the plastic deformation demonstrated by two commonly used suture materials can be reduced by manual pre-tensioning. Twenty sutures of both Prolene 3/0 (Ethicon, UK) and Ethibond 3/0 (Excel, Johnson and Johnson, UK) were tested. Half of the sutures in each group were manually pre-tensioned prior to knot tying and half were knotted without pre-tensioning. All knots were standard surgical knots with six throws. The suture lengths were measured before and after a standardised cyclical loading regime on an Instron tensile tester. The regime was designed to represent the finger flexion forces produced in a typical rehabilitation programme. All sutures were subsequently tested to their ultimate tensile strength. After cyclical loading the pre-tensioned sutures demonstrated a mean increase in suture length of 0.7% (range 0.1-1.9%). The sutures not pre-tensioned showed a mean increase of 5.4% (range 3.3-7%). This equates to 87% less plastic deformation (p <0.05 Students' T-test) upon pre-tensioning. There were no differences with Ethibond. Pre-tensioning had no effect on ultimate tensile strength for either group. Manual pre-tensioning reduces plastic deformation in Prolene 3/0 sutures without affecting the ultimate tensile strength. This simple technique could theoretically diminish gap formation at the site of a tendon repair

No, not my mother, but metal-on-metal (MoM) hips! My involvement in the DEFENSE side of MoM hips has allowed me the luxury of reflection and continued study on the basic and clinical science of this particular wear couple. Much of what I have learned is relevant to other articular couples, and might help you in your next THR. No amount of in vitro laboratory testing can replicate or predict in vivo behavior of a particular wear couple. (Mother Nature always has something new to teach us!) Although MoM implants went through complete pre-market evaluation and approval in both the US and EU, the process is inadequate and does not assure safety or success of new designs and materials. Two year results obtained in pre-market (IDE) studies are of insufficient follow-up for accurate evaluation of new materials or designs. Be conservative! Be neither the first, nor the last, to embrace new technology!. Clinical experience and retrieval analysis of MoM devices has revealed factors that are not as apparent for other wear couples such as metal-on-polyethylene (MoP), or ceramic-on-ceramic (CoC). For instance:. All THR's are at risk of micro-lateralization, or displacement of the femoral head from the acetabular wear couple during swing phase, resulting in edge loading. In addition, impingement or displacement related to component malposition or failure to balance the soft tissues about the hip can produce subluxation, producing edge loading and accelerated wear. In the case of MoM implants, the tribology and wear properties of MoM produce identifiable wear scars; all MoM designs appear to be subject to these phenomena. However, evidence now exists that both MoP and CoC wear couples are at similar risk for accelerated wear, although at different rates than MoM. Hard-on-hard wear couples (ceramic, metal) are less tolerant of edge loading than hard-on-soft (e.g., MoP or CoP) wear couples, and therefore require a higher degree of surgical precision in implant placement and reconstruction of the soft tissue balance of the hip. One of the previously unrecognised factors that can change relative implant position (and therefore, the risk of subluxation or edge loading) is the effect of the lumbar spine on apparent acetabular component position (e.g., changes between sitting, standing, or lying prone). This is largely due to the effect of lumbar spine flexibility, as shown in both orthogonal x-ray (“EOSr”) studies, and dynamic CAT scan studies. There is currently no validated algorithm or technique to assess these factors; however, surgeon awareness and at least clinical assessment preoperatively may result in better positioning of implants. Femoral component position can also have a major effect of the risk of impingement or subluxation of the femoral head; the combined anteversion concept of Dorr et al. should be rigorously adhered during THR. Other issues such as fretting corrosion associated with large diameter femoral heads and tissue response to wear debris may not be anticipated until a very large cohort population is available for examination and analysis. No matter how extensive in vitro testing may be, only clinical experience and retrieval analysis can provide the ultimate reassurance as to the success of a new design or material

Introduction. Successful tendon repairs are reliant on the suture material having high tensile strength, no or little tissue response, good handling characteristics and little elastic/plastic deformation. Plastic deformation contributes to gap formation at a tendon repair site. Previous research has shown a gap greater than 4mm is likely to fail. Pre-tensioning is a commonly used method to improve the handling properties of sutures. This study investigates whether the plastic deformation demonstrated by two suture materials used in flexor tendon repair is affected by manual pre-tensioning. Material/Methods. Twenty lengths of 3/0 Prolene (Ethicon, UK) and 3/0 Ethibond Excel (Ethicon, UK) were selected. Half of the sutures in each group were manually pre-tensioned (longitudinal stretch of 15N for 3s) prior to knot tying (standard surgical knot with six throws) and half were knotted without pre-tensioning. The suture lengths were measured before and after a standardised cyclical loading regime on a tensile tester. The regime was designed to represent the finger flexion forces produced in an active rehabilitation programme after tendon repair. All sutures were subsequently tested to their ultimate tensile strength. Results. After cyclical loading the Prolene sutures not pre-tensioned showed a mean increase in suture length of 5.4% (range 3.3-7%). The pre-tensioned Prolene sutures demonstrated a mean increase of 0.7% (range 0.1-1.9%). This equates to 87% less plastic deformation (p < 0.05 Students' T-test) with pre-tensioning. There were no differences with Ethibond. Pre-tensioning had no effect on ultimate tensile strength for either group. Conclusion. Manual pre-tensioning reduces plastic deformation in Prolene 3/0 sutures without affecting the ultimate tensile strength. This simple technique could theoretically diminish gap formation at the site of a tendon repair

Introduction: The suture properties associated with a successful tendon repair are: high tensile strength, little tissue response, good handling characteristics and minimal plastic deformation. Plastic deformation contributes to gap formation at a tendon repair site. Gaps greater than 4mm are likely to fail. This study investigates whether the plastic deformation demonstrated by two commonly used suture materials can be reduced by manual pre-tensioning. Methods: Twenty sutures of both Prolene 3/0 (Ethicon, UK) and Ethibond 3/0 (Excel, Johnson and Johnson, UK) were tested. Half of the sutures in each group were manually pre-tensioned prior to knot tying and half were knotted without pre-tensioning. All knots were standard surgical knots with six throws. The suture lengths were measured before and after a standardised cyclical loading regime on an Instron tensile tester. The regime was designed to represent the finger flexion forces produced in a typical rehabilitation programme. All sutures were subsequently tested to their ultimate tensile strength. Results: After cyclical loading the pre-tensioned sutures demonstrated a mean increase in suture length of 0.7% (range 0.1–1.9%). The sutures not pre-tensioned showed a mean increase of 5.4% (range 3.3–7%). This equates to 87% less plastic deformation (p < 0.05 Students’ T-test) upon pre-tensioning. There were no differences with Ethibond. Pre-tensioning had no effect on ultimate tensile strength for either group. Conclusions: Manual pre-tensioning reduces plastic deformation in Prolene 3/0 sutures without affecting the ultimate tensile strength. This simple technique could theoretically diminish gap formation at the site of a tendon repair

Metal and their alloys have been widely used as implantable materials and prostheses in orthopaedic surgery. However, concerns exist as the metal nanoparticles released from wear of the prostheses cause clinical complications and in some cases result in catastrophic host tissue responses. The mechanism of nanotoxicity and cellular responses to wear metal nanoparticles are largely unknown. The aim of this study was to characterise macrophage phagocytosed cobalt/chromium metal nanoparticles both in vitro and in vivo, and investigate the consequent cytotoxicity. Two types of macrophage cell lines, murine RAW246.7 and human THP-1s were used for in vitro study, and tissues retrieved from pseudotumour patients caused by metal-on-metal hip resurfacing (MoMHR) were used for ex vivo observation. Transmission electron microscopy (TEM), scanning electron microscopy (SEM) in combination with backscatter, energy-disperse X-ray spectrometer (EDS), focused ion beam (FIB) were employed to characterise phagocytosed metal nanoparticles. Alamar blue assay, cell viability assays in addition to confocal microscopy in combination with imaging analysis were employed to study the cytotoxiticy in vitro. The results showed that macrophages phagocytosed cobalt and chromium nanoparticles in vitro and the phagocytosed metal particles were confirmed by backscatter SEM+EDS and FIB+EDS. these particles were toxic to macrophages at a dose dependent manner. The analysis of retrieved tissue from revision of MoMHR showed that cobalt/chromium metal nanoparticles were observed exclusively in living macrophages and fragments of dead macrophages, but they were not seen within either live or dead fibroblasts. Dead fibroblasts were associated with dead and disintegrated macrophages and were not directly in contact with metal particles; chromium but not cobalt was the predominant component remaining in tissue. We conclude that as an important type of innate immune cells and phagocytes, macrophages play a key role in metal nanoparticles related cytotoxicity. Metal nanoparticles are taken up mainly by macrophages. They corrode in an acidic environment of the phagosomes. Cobalt that is more soluble than chromium may release inside macrophages to cause death of individual nanoparticle-overloaded macrophages. It is then released into the local environment and results in death of fibroblasts and is subsequently leached from the tissue

During the last decades numerous studies have reported the critical impact of physical activity on bone repair. While most studies have evaluated the tissue response to the local mechanical environment within the fracture gap, there is a lack of information on the systemic role of physical activity during fracture healing. Therefore, the aim of this study was to standardize the mechanical environment in the fracture gap by developing a rotationally and axially stable murine fracture model, and thereby to analyze the systemic influence of physical activity on early bone repair. After stable fixation of a closed femoral fracture, mice (n=18) were housed in cages supplied with running wheels (running distance > 500m/d). At 2 weeks animals were sacrificed and bones were prepared for histomorphometric (n=7), biomechanical (n=7), and protein biochemical analyses (n=4). Additional mice (n=22), which were housed in standard cages, served as controls. Histomorphometric evaluation showed no influence of increased physical activity on bone repair in terms of callus size and tissue composition. Accordingly, also biomechanical testing of the callus revealed no differences between both groups in rotational stiffness, peak rotation angle, and load at failure. Western blot analyses demonstrated no alterations in callus expression of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) after daily running when compared to controls. We conclude that increased physical activity under standardized mechanical conditions in the fracture gap does not affect early bone repair in mice

Metal-on-metal (MOM) hip resurfacings release chromium and cobalt wear debris into the surrounding joint. The hip tissue taken from failed MOM hips shows specific histological features including a subsurface band-like infiltrate of macrophages with particulate inclusions, perivascular lymphocytic infiltrate and fibrin exudation. This tissue response has been called Aseptic Lymphocytic Vasculitis Associated Lesion (ALVAL). There is a recognised carcinogenic potential associated with hexavalent chromium and epidemiological data from first generation MOM arthroplasties may suggest an increased incidence of haematological malignancy. The ALVAL type reaction includes a marked proliferation of lymphocytes in the perivascular space and thorough investigation of this lymphocytic response is warranted. This study aims to further characterise the lymphocytic infiltrate using immunohistochemistry and to test clonality using polymerase chain reaction (PCR). Tissues from revised all cause failed MOM hip arthroplasties (n=77) were collected and analysed initially using routine H&E staining. Those that met the diagnostic criteria of ALVAL described above (n=34) were further stained with a panel of immunohistochemical markers (CD3, CD4, CD8 (T-cell markers) and CD20 (B-cell marker)). 10 representative ALVAL cases were selected and sent for gene rearrangement studies using PCR to determine whether the lymphocytes were polyclonal or monoclonal in nature. The analysis of the lymphocytic aggregates in ALVAL, showed a mixed population of B and T cells. Within the aggregates, there was a predominance of B cells (CD20) over T cells (CD3). Of the 10 cases which were analysed by PCR, 7 were suitable for interpretation. None of these cases showed evidence of monoclonal lymphocyte proliferation. The carcinogenic potential of wear debris from MOM hips, particularly affecting the haematopoietic system should be investigated. This study has shown a predominantly B-lymphocyte response in tissues surrounding MOM hips which is polyclonal. Although the numbers are small, the study suggests an immune mediated response in MOM hip tissue and excludes a neoplastic proliferation. However, long term follow up of patients with MOM hips may be prudent