Pro-osteogenic topographical cues promote early activation of osteoprogenitor differentiation via enhanced TGFß, Wnt, and Notch signaling.

OBJECTIVES: Titanium implant surfaces with modified topographies have improved osteogenic properties in vivo. However, the molecular mechanisms remain obscure. This study explored the signaling pathways responsible for the pro-osteogenic properties of micro-roughened (SLA) and chemically/nanostructurally (modSLA) modified titanium surfaces on human alveolar bone-derived osteoprogenitor cells (BCs) in vitro. MATERIALS AND METHODS: The activation of stem cell signaling pathways (TGFß/BMP, Wnt, FGF, Hedgehog, Notch) was investigated following early exposure (24 and 72 h) of BCs to SLA and modSLA surfaces in the absence of osteogenic cell culture supplements. RESULTS: Key regulatory genes from the TGFß/BMP (TGFBR2, BMPR2, BMPR1B, ACVR1B, SMAD1, SMAD5), Wnt (Wnt/ß-catenin and Wnt/Ca(2+) ) (FZD1, FZD3, FZD5, LRP5, NFATC1, NFATC2, NFATC4, PYGO2, LEF1) and Notch (NOTCH1, NOTCH2, NOTCH4, PSEN1, PSEN2, PSENEN) pathways were upregulated on the modified surfaces. These findings correlated with a higher expression of osteogenic markers bone sialoprotein (IBSP) and osteocalcin (BGLAP), and bone differentiation factors BMP2, BMP6, and GDF15, as observed on the modified surfaces. CONCLUSIONS: These findings demonstrate that the activation of the pro-osteogenic cell signaling pathways by modSLA and SLA surfaces leads to enhanced osteogenic differentiation as evidenced after 7 and 14 days culture in osteogenic media and provides a mechanistic insight into the superior osseointegration on the modified surfaces observed in vivo.

A population-based epidemiological and health economic analysis of fracture-related infection.

Aims: The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI). Methods: This is a retrospective cohort study of operatively managed orthopaedic trauma patients from 1 January 2007 to 31 December 2016, performed in Queensland, Australia. Record linkage was used to develop a person-centric, population-based dataset incorporating routinely collected administrative, clinical, and health economic information. The FRI group consisted of patients with International Classification of Disease 10th Revision diagnosis codes for deep infection associated with an implanted device within two years following surgery, while all others were deemed not infected. Demographic and clinical variables, as well as healthcare utilization costs, were compared. Results: There were 111,402 patients operatively managed for orthopaedic trauma, with 2,775 of these (2.5%) complicated by FRI. The development of FRI had a statistically significant association with older age, male sex, residing in rural/remote areas, Aboriginal or Torres Strait Islander background, lower socioeconomic status, road traffic accident, work-related injuries, open fractures, anatomical region (lower limb, spine, pelvis), high injury severity, requiring soft-tissue coverage, and medical comorbidities (univariate analysis). Patients with FRI had an eight-times longer median inpatient length of stay (24 days vs 3 days), and a 2.8-times higher mean estimated inpatient hospitalization cost (AU$56,565 vs AU$19,773) compared with uninfected patients. The total estimated inpatient cost of the FRI cohort to the healthcare system was AU$156.9 million over the ten-year period. Conclusion: The results of this study advocate for improvements in trauma care and infection management, address social determinants of health, and highlight the upside potential to improve prevention and treatment strategies.

Downsizing and minimising medialisation of the acetabular component: Novel technique to preserve bone in THA.

Standard practice for acetabular component placement in total hip arthroplasty (THA) is to medialise the acetabular component. Bone preservation techniques during primary THA are beneficial for possible future revisions. The goal of this study is to examine the effect of downsizing and minimising medialisation of the acetabular component on bone resection volume. The volume of bone resected during acetabular preparation for different sizes of components was calculated and the volume of bone preserved by downsizing the cup was determined. Minimising medialisation of the acetabular component by 1-3 mm from the true floor was calculated. Absolute values and percentage of bone volume preserved when acetabular components are downsized or less medialised is presented. Downsizing the acetabular component by one size (2 mm) preserves between 2.6 cm3 (size 40 vs 42) and 8.4 cm3 (size 72 vs 74) of bone volume and consistently reduces resected bone volume by at least 35% (range 35.2%-37.5%). Similarly, reducing medialisation of a 56 mm acetabular cup (as an example of a commonly implanted component) by 3 mm reduces bone loss by 5.9 cm3- 44% less bone volume resection. Downsizing and minimising medialisation of the cup in THA substantially preserves bone which may benefit future revision surgeries. Surgeons could consider implanting the smallest acceptable acetabular shell to preserve bone without compromising on head size.

Objective Measures of Gaze Behaviors and the Visual Environment during Near-Work Tasks in Young Adult Myopes and Emmetropes.

Purpose: To objectively quantify near-work gaze behaviors and the visual environment during reading tasks performed on a smartphone and on paper in both indoor and outdoor environments in myopes and emmetropes. Methods: A novel wearable gaze and viewing distance tracking device was used to quantify near-work gaze behaviors (focusing demand) and the visual environment (20° peripheral scene relative defocus) during a series of reading tasks. Data from nine myopes (mean age, 21 ± 1.4 years) and 10 emmetropes (21 ± 0.8 years) were analyzed. Five-minute reading tasks (matched for font type and size) were performed under four conditions: reading from a smartphone indoors, paper indoors, smartphone outdoors, and paper outdoors. Results: A significantly greater focusing demand (closer viewing distance) was found with smartphone-based reading (mean, 3.15 ± 0.74 D) compared to paper-based reading (2.67 ± 0.48 D) (P < 0.001), with the differences being greatest for myopic participants (P = 0.04). Smartphone reading was also associated with greater peripheral scene relative myopic defocus (P < 0.001). Although near-work behaviors were similar between environments, significantly more relative myopic defocus was found at the start of the paper-based task when performed outdoors compared to indoors (P = 0.02). Conclusions: Significant differences in focusing demand and scene relative defocus within a 20° field were found to be associated with reading tasks performed on a smartphone and paper in indoor and outdoor environments. Translational Relevance: These findings highlight the complex interaction between near-work behaviors and the visual environment and demonstrate that factors of potential importance to myopia development vary between paper-based and smartphone-based near tasks.

The effects of gender, age, and videogame experience on performance and experiences with a surgical robotic arm: an exploratory study with general public.

Robotic surgery is increasing in prevalence, thanks to its potential benefits for patients (e.g., reduced blood loss) and surgeons (e.g., ergonomics). It is important to know what inherent characteristics of potential surgeons may facilitate robotic surgery training and performance. Findings from previous studies indicate videogames can be inexpensive tools that help improve hand-eye coordination, coordination of 3-D movements with 2-D images, and spatial orientation. In the context of robotic-assisted knee arthroscopy using a MAKO robotic arm, this study explored performance and subjective experiences of novices (N = 104) with a fake bone shaving task at a public event. Participants' performance was measured based on how much of the bone they successfully shaved. Findings showed that duration of videogame play per week was negatively related to performance with the robotic arm. Male and female participants performed similarly on the bone shaving task, and reported similar difficulty with and enjoyment of the task. However, female participants who played videogames performed better than those who did not play videogames. Participants who were younger than 11 had the worst performance and the most difficulty with the robotic arm. Overall, the findings indicate that the effect of videogame experience on the performance with the robotic arm may differ based on gender and age. This has implications on the length of training for surgeons of different gender using videogames and other emerging technologies.

Visual Localisation for Knee Arthroscopy.

PURPOSE  : Navigation in visually complex endoscopic environments requires an accurate and robust localisation system. This paper presents the single image deep learning based camera localisation method for orthopedic surgery. METHODS  : The approach combines image information, deep learning techniques and bone-tracking data to estimate camera poses relative to the bone-markers. We have collected one arthroscopic video sequence for four knee flexion angles, per synthetic phantom knee model and a cadaveric knee-joint. RESULTS  : Experimental results are shown for both a synthetic knee model and a cadaveric knee-joint with mean localisation errors of 9.66mm/0.85[Formula: see text] and 9.94mm/1.13[Formula: see text] achieved respectively. We have found no correlation between localisation errors achieved on synthetic and cadaveric images, and hence we predict that arthroscopic image artifacts play a minor role in camera pose estimation compared to constraints introduced by the presented setup. We have discovered that the images acquired for 90°and 0°knee flexion angles are respectively most and least informative for visual localisation. CONCLUSION  : The performed study shows deep learning performs well in visually challenging, feature-poor, knee arthroscopy environments, which suggests such techniques can bring further improvements to localisation in Minimally Invasive Surgery.

Single-stage revision of MRSA orthopedic device-related infection in sheep with an antibiotic-loaded hydrogel.

Local antimicrobial therapy is an integral aspect of treating orthopedic device-related infection (ODRI), which is conventionally administered via polymethyl-methacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibiotic-loaded hydrogel in a single-stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture-negative. Antibiotic delivery via hydrogel resulted in 10-100 times greater local concentrations for the first 2-3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.

The influence of biomechanical stability on bone healing and fracture-related infection: the legacy of Stephan Perren.

Bone healing is a complicated process of tissue regeneration that is influenced by multiple biological and biomechanical processes. In a minority of cases, these physiological processes are complicated by issues such as nonunion and/or fracture-related infection (FRI). Based on a select few in vivo experimental animal studies, construct stability is considered an important factor influencing both prevention and treatment of FRI. Stephan Perren played a pivotal role in the evolution of our current understanding of the critical relationship between biomechanics, fracture healing and infection. Furthermore, his concept of strain theory and the process of fracture healing is familiar to several generations of surgeons and has influenced implant development and design for the past 50 years. In this review we describe the role of biomechanical stability on fracture healing, and provide a detailed analysis of the preclinical studies addressing this in the context of FRI. Furthermore, we demonstrate how Perren's concepts of stability are still applied to current surgical techniques to aid in the prevention and treatment of FRI. Finally, we highlight the key knowledge gaps in the underlying basic research literature that need to be addressed as we continue to optimize patient care.

Fracture-related infection: current methods for prevention and treatment.

Introduction: Fracture-related infection (FRI) is a serious complication related to orthopedic trauma, both from an infectious disease and a surgical point of view. The lack of scientific data with respect to diagnostic criteria and treatment principles of this entity has hampered efforts for an evidence-based approach and, as such, practices to prevent and treat FRI are often extrapolated from peri-prosthetic joint infection (PJI) literature. Recently, consensus guidelines were developed with respect to prevention, diagnosis and treatment of FRI.Areas covered: This review will define FRI and approaches to prevent and treat this complication will be discussed, with an emphasis on antimicrobial and surgical considerations. Guidelines focusing on FRI will be highlighted and aspects of pre-clinical research with imminent translational potential described.Expert opinion: New strategies are currently under investigation to improve the outcome of this sometimes-devastating complication. Local delivery of antimicrobials seems to be a promising approach; however, further high-quality clinical research is necessary to demonstrate efficacy. Delivery mechanisms for local antimicrobials include polymethyl methacrylate, implant coatings, collagen fleece, hydrogels and ceramics. The reintroduction of antimicrobials such as bacteriophage therapy has demonstrated promise in the management of drug-resistant organisms.

Bacterial Profile, Multi-Drug Resistance and Seasonality Following Lower Limb Orthopaedic Surgery in Tropical and Subtropical Australian Hospitals: An Epidemiological Cohort Study.

We aimed to describe the epidemiology, multi-drug resistance and seasonal distribution of bacteria cultured within 12 months following lower limb orthopaedic surgery in tropical and subtropical Australian hospitals between 2010 and 2017. We collected data from four tropical and two subtropical hospitals. Categorical variables were examined using the Pearson Chi-squared test or Fisher's Exact test, and continuous variables with the Student t-test or Mann-Whitney U test. A Poisson regression model was used to examine the relationship between season, weather and the incidence of Staphylococcus and nonfermentative species. We found that at tropical sites, nonfermenters (Pseudomonas aeruginosa and Acinetobacter baumannii) were more common (28.7% vs. 21.6%, p = 0.018), and patients were more likely to culture multi-drug-resistant (MDR) nonfermenters (11.4% vs. 1.3%, p = 0.009) and MDR Staphylococcus aureus (35.9% vs. 24.6%, p = 0.006). At tropical sites, patients were more likely to be younger (65.9 years vs. 72.0, p = < 0.001), male (57.7% vs. 47.8%, p = 0.005), having knee surgery (45.3% vs. 34.5%, p = 0.002) and undergoing primary procedures (85.0% vs. 73.0%, p = < 0.001). Species were similar between seasons in both tropical and subtropical hospitals. Overall, we found that following lower limb orthopaedic surgery in tropical compared with subtropical Australia, patients were more likely to culture nonfermenters and some MDR species.

Deep Learning for US Image Quality Assessment Based on Femoral Cartilage Boundary Detection in Autonomous Knee Arthroscopy.

Knee arthroscopy is a complex minimally invasive surgery that can cause unintended injuries to femoral cartilage or postoperative complications, or both. Autonomous robotic systems using real-time volumetric ultrasound (US) imaging guidance hold potential for reducing significantly these issues and for improving patient outcomes. To enable the robotic system to navigate autonomously in the knee joint, the imaging system should provide the robot with a real-time comprehensive map of the surgical site. To this end, the first step is automatic image quality assessment, to ensure that the boundaries of the relevant knee structures are defined well enough to be detected, outlined, and then tracked. In this article, a recently developed one-class classifier deep learning algorithm was used to discriminate among the US images acquired in a simulated surgical scenario on which the femoral cartilage either could or could not be outlined. A total of 38 656 2-D US images were extracted from 151 3-D US volumes, collected from six volunteers, and were labeled as "1" or as "0" when an expert was or was not able to outline the cartilage on the image, respectively. The algorithm was evaluated using the expert labels as ground truth with a fivefold cross validation, where each fold was trained and tested on average with 15 640 and 6246 labeled images, respectively. The algorithm reached a mean accuracy of 78.4% ± 5.0, mean specificity of 72.5% ± 9.4, mean sensitivity of 82.8% ± 5.8, and mean area under the curve of 85% ± 4.4. In addition, interobserver and intraobserver tests involving two experts were performed on an image subset of 1536 2-D US images. Percent agreement values of 0.89 and 0.93 were achieved between two experts (i.e., interobserver) and by each expert (i.e., intraobserver), respectively. These results show the feasibility of the first essential step in the development of automatic US image acquisition and interpretation systems for autonomous robotic knee arthroscopy.

Ultrasound guidance in minimally invasive robotic procedures.

In the past decade, medical robotics has gained significant traction within the surgical field. While the introduction of fully autonomous robotic systems for surgical procedures still remains a challenge, robotic assisted interventions have become increasingly more interesting for the scientific and clinical community. This happens especially when difficulties associated with complex surgical manoeuvres under reduced field of view are involved, as encountered in minimally invasive surgeries. Various imaging modalities can be used to support these procedures, by re-creating a virtual, enhanced view of the intervention site. Among them, ultrasound imaging showed several advantages, such as cost effectiveness, non-invasiveness and real-time volumetric imaging. In this review we comprehensively report about the interventional applications where ultrasound imaging has been used to provide guidance for the intervention tools, allowing the surgeon to visualize intra-operatively the soft tissue configuration in real-time and to compensate for possible anatomical changes. Future directions are also discussed, in particular how the recent developments in 3D/4D ultrasound imaging and the introduction of advanced imaging capabilities (such as elastography) in commercially available systems may fulfil the unmet needs towards fully autonomous robotic interventions.

A mixed-methods retrospective study: 10 years of diabetic retinopathy screening in urban Aboriginal and Torres Strait Islander primary care.

This research applies a mixed-method approach to retrospectively study the history of diabetic retinopathy (DR) screening in an urban Aboriginal and Torres Strait Islander general practice. Data from administrative practice software and publications were extracted and presented as a timeline data visualisation to staff, in six focus groups. Eighteen key staff from the Southern Queensland Centre of Excellence in Aboriginal and Torres Strait Islander Primary Health Care (CoE) were purposively recruited. The main outcome measures were retrospective administrative practice data, publications and staff interpretations regarding DR screening at the CoE. The CoE DR screening initially increased screening rates to 93%. Participants reported that CoE DR screening provides eye care from screening to treatment; all annual care is provided in one appointment; and in a client-focussed environment. From 2012 to 2016, the number of regular CoE clients with diabetes increased by 46%. Consequently, DR screening rates dropped from 44% to 22%. Participants' recognised the service could reach its full potential if it implements continuous quality improvement focussed on client experience, using rigorous data and supported by engaged staff. Initial investment in setting-up DR screening is not enough, instead ongoing quality improvement is integral to a sustainable, successful service long-term.

Association between higher ambient temperature and orthopaedic infection rates: a systematic review and meta-analysis.

INTRODUCTION: Many infectious diseases display seasonal variation corresponding with particular conditions. In orthopaedics a growing body of evidence has identified surges in post-operative infection rates during higher temperature periods. The aim of this research was to collate and synthesize the current literature on this topic. METHODS: A systematic review and meta-analysis was performed using five databases (PubMed, Embase, CINAHL, Web of Science and Central (Cochrane)). Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. Odds ratios (ORs) were calculated from monthly infection rates and a pooled OR was generated using the DerSimonian and Lairds method. A protocol for this review was registered with the National Institute for Health Research International Prospective Register of Systematic Reviews (CRD42017081871). RESULTS: Eighteen studies analysing over 19 000 cases of orthopaedic related infection met inclusion criteria. Data on 6620 cases and 9035 controls from 12 studies were included for meta-analysis. The pooled OR indicated an overall increased odds of post-operative infection for patients undergoing orthopaedic procedures during warmer periods of the year (pooled OR 1.16, 95% confidence interval 1.04-1.30). CONCLUSION: A small but significantly increased odds of post-operative infection may exist for orthopaedic patients who undergo procedures during higher temperature periods. It is hypothesized that this effect is geographically dependent and confounded by meteorological factors, local cultural variables and hospital staffing cycles.

Unlocking the Value of Literature in Health Co-Design: Transforming Patient Experience Publications into a Creative and Accessible Card Tool.

BACKGROUND: A wealth of peer-reviewed data exists regarding people's health experience, yet practical ways of using the data to understand patients' experiences and to inform health co-design are needed. OBJECTIVE: This study aims to develop an applied and pragmatic method for using patient experience literature in co-design by transforming it into an accessible and creative co-design tool. METHOD: A scoping literature review of the CINAHL, MEDLINE, PsycINFO and PubMed electronic databases was conducted from January 2011 through August 2016. Qualitative publications regarding the experience of living with diabetes in Australia were selected. The Results section of each paper was extracted and affinity analysis was applied to identify insights into the health experience. These insights were developed into a card tool for use in health co-design activities. RESULTS: Thirteen relevant papers were identified from the review, and affinity analysis of the Results sections of these papers lead to the identification of 85 insights, from 'Shock of diagnosis' (Insight 1), to 'Delay seeking care' (Insight 9), to 'Assess the quality of care' (Insight 28), to 'Avoid or adapt habits' (Insight 78). Each insight was developed into an individual card, which included a high-level theme, insight, quote and a link back to the literature, together making up the Health Experience Insight Cards, Living with Diabetes Edition. CONCLUSIONS: This was the first study to develop a method for transforming existing patient experience literature into a creative tool for health improvement. The Health Experience Insight Cards collate the diverse experiences of over 300 people living with diabetes in Australia, from 13 studies. Health improvement teams can use the 'Living with Diabetes Edition' cards or they can follow this pragmatic method to create their own cards focused on other health experiences to facilitate person-focused health improvements.

Glare-free retinal imaging using a portable light field fundus camera.

We present the retinal plenoptoscope, a novel light field retinal imaging device designed to overcome many of the problems that limit the use of portable non-mydriatic fundus cameras, including image quality and lack of stereopsis. The design and prototype construction of this device is detailed and the ideal relationship between the eye pupil, system aperture stop and micro-image separation is investigated. A comparison of the theoretical entrance pupil size, multi-view baseline and depth resolution indicates that a higher degree of stereopsis is possible than with stereo fundus cameras. We also show that the effects of corneal backscatter on image quality can be removed through a novel method of glare identification and selective image rendering. This method is then extended to produce glare-free depth maps from densely estimated depth fields, creating representations of retinal topography from a single exposure. These methods are demonstrated on physical models and live human eyes using a prototype device based on a Lytro Illum consumer light field camera. The Retinal Plenoptoscope offers a viable, robust modality for non-mydriatic color and 3-D retinal imaging.

Orthopaedic surgeon attitudes towards current limitations and the potential for robotic and technological innovation in arthroscopic surgery.

PURPOSE: To determine the perceptions of surgeons at both consultant and resident level to the difficulties of performing knee arthroscopy and to determine their willingness to adopt robotic technology. METHODS: A questionnaire was designed to discern the attitude of orthopaedic consultants and residents to the technical challenges of performing knee arthroscopy and the possible role of robotically enhanced surgery. The questionnaire included 31 questions across five key domains. RESULTS: Iatrogenic damage to articular cartilage was thought to occur in at least 1 in 10 cases by 50% of respondents with 15% believing that it occurred in every case. One hundred or more procedures were thought to be necessary to overcome the learning curve by 40% of respondents and 77.5% believed that 50 procedures or above were necessary. Ninety-nine per cent of respondents agreed that higher technical skills would decrease unintended damage. Despite such difficulties with the procedure and no prior experience with robotic surgery, 47% of respondents see a role for semiautonomous arthroscopic systems in the future. CONCLUSIONS: Surgeons believe that knee arthroscopy is a difficult procedure with a long learning curve and a high incidence of iatrogenic cartilage damage. Many find it ergonomically challenging and have frustration with current tools and technology. CLINICAL RELEVANCE: This is the first study that highlights surgeons' difficulties performing knee arthroscopy despite the commonly held attitudes that it is a straightforward procedure. Systems that are able to decrease these problems should improve patients' outcomes and decrease the risk of harm.

A stimulatory effect of Ca3ZrSi2O9 bioceramics on cementogenic/osteogenic differentiation of periodontal ligament cells.

The regeneration of periodontal tissues to cure periodontitis remains a medical challenge. Therefore, it is of great importance to develop a novel biomaterial that could induce cementogenesis and osteogenesis in periodontal tissue engineering. Calcium silicate (Ca-Si) based ceramics have been found to be potential bioactive materials due to their osteostimulatory effect. Recently, it is reported that zirconium modified calcium-silicate-based (Ca3ZrSi2O9) ceramics stimulate cell proliferation and osteogenic differentiation of osteoblasts. However, it is unknown whether Ca3ZrSi2O9 ceramics possess specific cementogenic stimulation for human periodontal ligament cells (hPDLCs) in periodontal tissue regeneration in vitro. The purpose of this study was to investigate whether Ca3ZrSi2O9 ceramic disks and their ionic extracts could stimulate cell growth and cementogenic/osteogenic differentiation of hPDLCs; the possible molecular mechanism involved in this process was also explored by investigating the Wnt/ß-catenin signalling pathway of hPDLCs. Our results showed that Ca3ZrSi2O9 ceramic disks supported cell adhesion, proliferation and significantly up-regulated relative alkaline phosphatase (ALP) activity, cementogenic/osteogenic gene expression (CEMP1, CAP, ALP and OPN) and Wnt/ß-catenin signalling pathway-related genes (AXIN2 and CTNNB) for hPDLCs, compared to that of ß-tricalcium phosphate (ß-TCP) bioceramic disks and blank controls. The ionic extracts from Ca3ZrSi2O9 powders also significantly enhanced relative ALP activity, cementogenic/osteogenic and Wnt/ß-catenin-related gene expression of hPDLCs. The present results demonstrate that Ca3ZrSi2O9 ceramics are capable of stimulating cementogenic/osteogenic differentiation of hPDLCs possibly via activation of the Wnt/ß-catenin signalling pathway, suggesting that Ca3ZrSi2O9 ceramics have the potential to be used for periodontal tissue regeneration.

Phenotypic characterization of osteoarthritic osteocytes from the sclerotic zones: a possible pathological role in subchondral bone sclerosis.

Subchondral bone sclerosis is a well-recognised manifestation of osteoarthritis (OA). The osteocyte cell network is now considered to be central to the regulation of bone homeostasis; however, it is not known whether the integrity of the osteocyte cell network is altered in OA patients. The aim of this study was to investigate OA osteocyte phenotypic changes and its potential role in OA subchondral bone pathogenesis. The morphological and phenotypic changes of osteocytes in OA samples were investigated by micro-CT, SEM, histology, immunohistochemistry, TRAP staining, apoptosis assay and real-time PCR studies. We demonstrated that in OA subchondral bone, the osteocyte morphology was altered showing rough and rounded cell body with fewer and disorganized dendrites compared with the osteocytes in control samples. OA osteocyte also showed dysregulated expression of osteocyte markers, apoptosis, and degradative enzymes, indicating that the phenotypical changes in OA osteocytes were accompanied with OA subchondral bone remodelling (increased osteoblast and osteoclast activity) and increased bone volume with altered mineral content. Significant alteration of osteocytes identified in OA samples indicates a potential regulatory role of osteocytes in subchondral bone remodelling and mineral metabolism during OA pathogenesis.