Search

Several lines of research indicate that osteoarthritis (OA) is not only a joint disorder associated with mechanical stress and aging but also a 'metabolic syndrome' in which several risk factors work together to contribute to disease initiation and/or development. One such metabolic risk factor could be high cholesterol levels in the body. Even though high cholesterol level is a well-known risk factor for cardiovascular disorders, its possible role in musculoskeletal diseases, particularly OA, is not clear. The authors discuss the fundamental viewpoints on cholesterol involvement in the pathogenesis of OA, stressing the need for understanding the molecular mechanisms behind this association. This is the area of research needed to provide knowledge on how one should live to prevent OA development as well as to suggest new targets for drug therapy. [ABSTRACT FROM AUTHOR]

Sir James MacDonald of Knockrinsay is best known for his leadership of the 'Islay Rising' of 1615. Various strands of evidence are here brought together to reveal an individual of significance, controversy, and complexity. Sir James lived in relative comfort with King James VI at Edinburgh and London, but for eleven years he was imprisoned in the dungeon of Edinburgh Castle until he made his daring escape in 1615. Although possessed of a natural charisma, Sir James was not the most adept political operator, and his family life was always turbulent. His career is here set against a wider backdrop of upheaval and transition in the Highlands, as many clans struggled for survival. The ultimate failure of the 'Islay Rising' and Sir James's exile in the Spanish Netherlands can be seen as a symbolic end of an era for the clans of the West Highlands and Islands of Scotland. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic, incurable and destructive joint disease that is characterized by chondrocyte hypertrophy and cartilage degradation. Angiogenesis, mediated by the action of vascular endothelial growth factor (VEGF), is known to be a contributing factor in the pathogenesis of OA. In this study, we use a lentivirus-based approach to investigate whether VEGF knockdown would be beneficial to chondrogenesis and could prevent or slow down OA progression. We first profiled cytokines in human OA cartilage using cytokine antibody arrays. This revealed that as many as 21 angiogenesis-related cytokines were significantly upregulated in severe OA cartilage compared to mild OA samples. Next, we infected chondrocytes with VEGF small hairpin RNA (shRNA) lentivirus (LV-VEGF shRNA) and treated these cells with tumour necrosis factor alpha (TNF-α) to induce hypertrophy. The results showed that inhibition of VEGF not only enhanced chondrogenic differentiation, but also protected chondrocytes from TNF-α-induced hypertrophy. We also found that knockdown of VEGF suppressed TNF-α-induced phosphorylation of ERK1/2 in chondrocytes. Furthermore, using a surgically induced OA rat model, we showed that VEGF inhibition delayed OA progression in animals given intra-articular injection of LV-VEGF shRNA. In conclusion, in this study, we have shown that VEGF knockdown can enhance chondrogenesis and prevent OA progression, thus providing evidence that inhibition of VEGF may be a potential therapeutic approach for OA patients. Key messages: [ABSTRACT FROM AUTHOR]

Background: The treatment for deep surgical site infection (SSI) following primary total hip arthroplasty (THA) varies internationally and it is at present unclear which treatment approaches are used in Australia. The aim of this study is to identify current treatment approaches in Queensland, Australia, show success rates and quantify the costs of different treatments. Methods: Data for patients undergoing primary THA and treatment for infection between January 2006 and December 2009 in Queensland hospitals were extracted from routinely used hospital databases. Records were linked with pathology information to confirm positive organisms. Diagnosis and treatment of infection was determined using ICD-10-AM and ACHI codes, respectively. Treatment costs were estimated based on AR-DRG cost accounting codes assigned to each patient hospital episode. Results: A total of n=114 patients with deep surgical site infection were identified. The majority of patients (74%) were first treated with debridement, antibiotics and implant retention (DAIR), which was successful in eradicating the infection in 60.3% of patients with an average cost of $13,187. The remaining first treatments were 1-stage revision, successful in 89.7% with average costs of $27,006, and 2-stage revisions, successful in 92.9% of cases with average costs of $42,772. Multiple treatments following 'failed DAIR' cost on average $29,560, for failed 1-stage revision were $24,357, for failed 2-stage revision were $70,381 and were $23,805 for excision arthroplasty. Conclusions: As treatment costs in Australia are high primary prevention is important and the economics of competing treatment choices should be carefully considered. These currently vary greatly across international settings. [ABSTRACT FROM AUTHOR]

Abstract: The periosteum plays an indispensable role in both bone formation and bone defect healing. In this study we constructed an artificial in vitro periosteum by incorporating osteogenic differentiated bone marrow stromal cells (BMSCs) and cobalt chloride (CoCl2)-treated BMSCs. The engineered periostea were implanted both subcutaneously and into skull bone defects in SCID mice to investigate ectopic and orthotopic osteogenesis and vascularization. After two weeks in subcutaneous and four weeks in bone defect areas, the implanted constructs were assessed for ectopic and orthotopic osteogenesis and vascularization by micro-CT, histomorphometrical and immunohistochemical methods. The results showed that CoCl2 pre-treated BMSCs induced higher degree of vascularization and enhanced osteogenesis within the implants in both ectopic and orthotopic areas. This study provided a novel approach using BMSCs sourced from the same patient for both osteogenic and pro-angiogenic purposes in constructing tissue engineered periosteum to enhance vascularized osteogenesis. [Copyright &y& Elsevier]

Abstract: In both physiological and pathological processes, periosteum plays a determinant role in bone formation and fracture healing. However, no specific report is available so far focusing on the detailed structural and major cellular differences between the periostea covering different bone surface in relation to ageing. The aim of this study is to compare the structural and cellular differences in diaphyseal and metaphyseal periostea in different aged rats using histological and immunohistochemical methods. Four female Lewis rats from each group of juvenile (7 weeks old), mature (7 months old) and aged groups (2 years old) were sacrificed and the right femur of each rat was retrieved, fixed, decalcified and embedded. Five-micrometer thick serial sagittal sections were cut and stained with Hematoxylin and Eosin, Stro-1 (stem cell marker), F4/80 (macrophage marker), TRAP (osteoclast marker) and vWF (endothelial cell marker). One-millimeter lengths of middle diaphyseal and metaphyseal periosteum were selected for observation. The thickness, total cell number and positive cell number for each antibody were measured and compared in each periosteal area and different aged groups. The results were subjected to two-way ANOVA and SNK tests. The results showed that the thickness and cell number in diaphyseal periosteum decreased with age (p <0.001). In comparison with diaphyseal area, the thickness and cell number in metaphyseal periosteum were much higher (p <0.001). There were no significant differences between the juvenile and aged groups in the thickness and cell number in the cambial layer of metaphyseal periosteum (p >0.05). However, the juvenile rats had more Stro1+, F4/80+ cells and blood vessels and fewer TRAP+ cells in different periosteal areas compared with other groups (p <0.001). The aged rats showed much fewer Stro1+ cells, but more F4/80+, TRAP+ cells and blood vessels in the cambial layer of metaphyseal periosteum (p <0.001). In conclusion, structure and cell population of periosteum appear to be both age-related and site-specific. The metaphyseal periosteum of aged rats seems more destructive than diaphyseal part and other age groups. Macrophages in the periosteum may play a dual important role in osteogenesis and osteoclastogenesis. [Copyright &y& Elsevier]

Abstract: Background: Relative indentation characteristics are commonly used for distinguishing between normal healthy and degraded cartilage. The application of this parameter in surgical decision making and an appreciation of articular cartilage biomechanics has prompted us to hypothesise that it is difficult to define a reference stiffness to characterise normal articular cartilage. Methods: This hypothesis is tested for validity by carrying out biomechanical indentation of articular cartilage samples that are characterised as visually normal and degraded relative to proteoglycan depletion and collagen disruption. Compressive loading was applied at known strain rates to visually normal, artificially degraded and naturally osteoarthritic articular cartilage and observing the trends of their stress–strain and stiffness characteristics. Findings: While our results demonstrated a 25% depreciation in the stiffness of individual samples after proteoglycan depletion, they also showed that when compared to the stiffness of normal samples only 17% lie outside the range of the stress–strain behaviour of normal samples. Interpretation: We conclude that the extent of the variability in the properties of normal samples, and the degree of overlap (81%) of the biomechanical properties of normal and degraded matrices demonstrate that indentation data cannot form an accurate basis for distinguishing normal from abnormal articular cartilage samples with consequences for the application of this mechanical process in the clinical environment. [Copyright &y& Elsevier]

Background: Evidence has strongly indicated that surface-active phospholipid (SAPL), or surfactant, lines the surface of cartilage and serves as a lubricating agent. Previous clinical study showed that a saturated phosphatidylcholine (SPC), dipalmitoyl-phosphatidylcholine (DPPC), was effective in the treatment of osteoarthritis, however recent studies suggested that the dominant SAPL species at some sites outside the lung are not SPC, rather, are unsaturated phosphatidylcholine (USPC). Some of these USPC have been proven to be good boundary lubricants by our previous study, implicating their possible important physiological roles in joint if their existence can be confirmed. So far, no study has been conducted to identify the whole molecule species of different phosphatidylcholine (PC) classes on the surface of cartilage. In this study we identified the dominant PC molecule species on the surface of cartilage. We also confirmed that some of these PC species possess a property of semipermeability. Methods: HPLC was used to analyse the PC profile of bovine cartilage samples and comparisons of DPPC and USPC were carried out through semipermeability tests. Results: It was confirmed that USPC are the dominant SAPL species on the surface of cartilage. In particular, they are Dilinoleoyl-phosphatidylcholine (DLPC), Palmitoyl-linoleoylphosphatidylcholine, (PLPC), Palmitoyl-oleoyl-phosphatidylcholine (POPC) and Stearoyl-linoleoylphosphatidylcholine (SLPC). The relative content of DPPC (a SPC) was only 8%. Two USPC, PLPC and POPC, were capable of generating osmotic pressure that is equivalent to that by DPPC. Conclusion: The results from the current study confirm vigorously that USPC is the endogenous species inside the joint as against DPPC thereby confirming once again that USPC, and not SPC, characterizes the PC species distribution at non-lung sites of the body. USPC not only has better anti-friction and lubrication properties than DPPC, they also possess a level of semipermeability that is equivalent to DPPC. We therefore hypothesize that USPC can constitute a possible addition or alternative to the current commercially available viscosupplementation products for the prevention and treatment of osteoarthritis in the future. [ABSTRACT FROM AUTHOR]

A macrophage infiltrate is commonly found in enlarging subchondral cysts in osteoarthrosis (OA) and the surrounding bone. To determine whether osteoclast differentiation by these cells contributes to the increase in the number of osteoclasts and bone resorption that accompanies OA cyst enlargement, we isolated macrophages from the wall of OA cysts and co-cultured them with osteoblast-like UMR106 cells in the presence or absence of 1,25(OH)[sub 2]D[sub 3] and M-CSF. After 14 days of incubation, co-cultures of UMR106 cells and cyst-derived macrophages showed evidence of osteoclast differentiation by expression of TRAP, VNR and formation of numerous lacunar pits. We found that, unlike osteoclast precursors in monocyte and other tissue macrophage populations, the addition of M-CSF to medium is not required for osteoclast differentiation. Our findings suggest that macrophage-osteoclast differentiation is one means whereby the osteolysis associated with the enlargement of OA cysts could be effected. [ABSTRACT FROM AUTHOR]

Articular cartilage function depends on the temporal and zonal distribution of coordinated metabolic regulation in chondrocytes. Emerging evidence shows the importance of cellular metabolism in the molecular control of the cartilage and its dysregulation in degenerative diseases like osteoarthritis (OA). Compared to most other tissues, chondrocytes are sparsely located in the extracellular matrix, lacking the typical proximity of neural, vascular, and lymphatic tissue. Making up under 5% of the total tissue weight of cartilage, chondrocytes have a relative deficiency of access to nutrients and oxygen, as well as limited pathways for metabolite removal. This makes cartilage a unique tissue with hypocellularity, prolonged metabolic rate, and tissue turnover. Studies in the past decade have shown that several pathways of central carbon metabolism are essential for cartilage homeostasis. Here, we summarised the literature findings on the role of cellular metabolism in determining the chondrocyte function and how this metabolic dysregulation led to cartilage aging in OA and provided an outlook on how the field may evolve in the coming years. Although the various energy metabolism pathways are inextricably linked with one another, for the purpose of this review, we initially endeavoured to examine them individually and in relative isolation. Subsequently, we comment on what is known regarding the integration and linked signalling pathways between these systems and the therapeutic opportunities for targeting OA metabolism. [ABSTRACT FROM AUTHOR]

Altered subchondral bone and articular cartilage interactions have been implicated in the pathogenesis of osteoarthritis (OA); however, the mechanisms remain unknown. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication. Herein, we investigated if OA subchondral bone derived exosomes alter transcriptional and bioenergetic signatures of chondrocytes. Exosomes were isolated and purified from osteoblasts of nonsclerotic or sclerotic zones of human OA subchondral bone and their role on the articular cartilage chondrocytes was evaluated by measuring the extent of extracellular matrix production, cellular bioenergetics, and the expression of chondrocyte activity associated marker genes. Exosomal microRNAs were analyzed using RNA sequencing and validated by quantitative real-time PCR and loss-of-function. In coculture studies, chondrocytes internalized OA sclerotic subchondral bone osteoblast derived exosomes and triggered catabolic gene expression and reduced chondrocyte-specific marker expression a phenomenon that is often observed in OA cartilage. RNA sequencing and miRNA profiling have identified miR-210-5p, which is highly enriched in OA sclerotic subchondral bone osteoblast exosomes, triggered the catabolic gene expression in articular cartilage chondrocytes. Importantly, we demonstrate that miR-210-5p suppresses the oxygen consumption rate of chondrocytes, altering their bioenergetic state that is often observed in OA conditions. These effects were markedly inhibited by the addition of a miR-210-5p inhibitor. Our study indicates that exosomes released by OA sclerotic subchondral bone osteoblasts plays a critical role in progression of cartilage degeneration and might be a potential target for therapeutic intervention in OA. [ABSTRACT FROM AUTHOR]

Investigates the influence of surface finish on fluid flow along the stem-cement interface of cemented femoral components in an in vitro model. Bone cement pressurization; Contribution of capillary flow to fluid movement; Electrostatic interaction between the metal and bone cement.

[Display omitted] Treatment of large bone defects, particularly bone non-union, remains a clinical challenge. The gold-standard bone substitute continues to be an autologous bone graft, which is difficult to be replaced with synthetic biomaterials. Considering these aspects, strategies should be formulated to develop advanced materials for functional bone regeneration. Recent studies have revealed that hematoma (the first tissue structure formed at the bone injury site) plays an essential role in bone healing. Hematoma consists of a fibrin clot, infiltrated immune cells, and tissue progenitor cells. It bridges the bone defect and provides a microenvironment for the interplay between hemostasis and the immune systems. Moreover, an ideal fibrin structure with appropriate fiber thickness and density could facilitate bone regeneration, and biomaterial implantation could affect fibrin structure. Meanwhile, immunoregulation plays an essential role in bone healing. In particular, materials inducing a shift from inflammatory to anti-inflammatory phenotypes in immune cells show enhanced osteoinductivity. More importantly, the interaction between hemostasis and the immune system should play a vital part in bone regeneration by determining both fibrin structure and bone healing microenvironment. Coagulants-triggered inflammation could, in turn, facilitate coagulation cascades, which form positive feedback to amplify both processes. Meanwhile, anti-coagulants neutralize coagulation and inhibit inflammation and thereby control the coagulation and inflammation to prevent thrombosis. The balance between coagulation–inflammation and anti-coagulation–anti-inflammation plays a determinant role in the fibrin structure and fibrinolysis process. The inflammation could be "quenched" gradually during this process, whereby a highly effective microenvironment for bone regeneration can be generated. Presently, there are limited biomaterial studies targeting the bone-healing hematoma, particularly the hemostasis–immune interplay. Considering this, this review summarizes the current materials for hemostasis and immunomodulation, and the critical role of the hemostasis–immune interaction in bone regeneration. It also proposes potential strategies to develop materials with the capacity to generate a highly effective bone healing hematoma, by modulating the hemostasis–immune interplay to maintain the balance between coagulation–inflammation and anti-coagulation–anti-inflammation. [ABSTRACT FROM AUTHOR]

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects. [ABSTRACT FROM AUTHOR]

Discusses the influence of the proximal femur anatomy on the formation of incomplete cement mantles in the sagittal femoral plane. Radiography of the proximal femur; Incidence of femoral osteolysis; Femoral neck retention.

Chondrogenic induction of bone-marrow-derived stromal cells (BMSCs) is typically accomplished with medium supplemented with growth factors (GF) from the transforming growth factor-beta (TGF-β)/bone morphogenetic factor (BMP) superfamily. In a previous study, we demonstrated that brief (1–3 days) stimulation with TGF-β1 was sufficient to drive chondrogenesis and hypertrophy using small-diameter microtissues generated from 5000 BMSC each. This biology is obfuscated in typical large-diameter pellet cultures, which suffer radial heterogeneity. Here, we investigated if brief stimulation (2 days) of BMSC microtissues with BMP-2 (100 ng/mL) or growth/differentiation factor (GDF-5, 100 ng/mL) was also sufficient to induce chondrogenic differentiation, in a manner comparable to TGF-β1 (10 ng/mL). Like TGF-β1, BMP-2 and GDF-5 are reported to stimulate chondrogenic differentiation of BMSCs, but the effects of transient or brief use in culture have not been explored. Hypertrophy is an unwanted outcome in BMSC chondrogenic differentiation that renders engineered tissues unsuitable for use in clinical cartilage repair. Using three BMSC donors, we observed that all GFs facilitated chondrogenesis, although the efficiency and the necessary duration of stimulation differed. Microtissues treated with 2 days or 14 days of TGF-β1 were both superior at producing extracellular matrix and expression of chondrogenic gene markers compared to BMP-2 and GDF-5 with the same exposure times. Hypertrophic markers increased proportionally with chondrogenic differentiation, suggesting that these processes are intertwined for all three GFs. The rapid action, or "temporal potency", of these GFs to induce BMSC chondrogenesis was found to be as follows: TGF-β1 > BMP-2 > GDF-5. Whether briefly or continuously supplied in culture, TGF-β1 was the most potent GF for inducing chondrogenesis in BMSCs. [ABSTRACT FROM AUTHOR]

BACKGROUND The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. METHODS In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. RESULTS A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical- site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P=0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83). CONCLUSIONS The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. [ABSTRACT FROM AUTHOR]

The article presents a study which found deterioration in the quality of the bone cement interface with time and encourages orthopedic surgeons to use mantle with minimum thickness of three millimeters in total knee replacement surgery. It puts emphasis on the need of studying the quality of the trabecular bone around both cemented and uncemented implants in order to understand the role of stress shielding, load transfer, and implant fixation techniques.

The article discusses the short-term outcomes and complications in obese patients undergoing hip and knee replacements. Complications for patients undergoing total joint replacement (TJR) will be difficult to determine if obesity is a risk factor for the conditions. Meanwhile, one of the problems in assessing outcomes after TJR is the improvement in pain and function from the index operation.

The financial viability of a cell and tissue-engineered therapy may depend on the compatibility of the therapy with mass production and cryopreservation. Herein, we developed a method for the mass production and cryopreservation of 3D cartilage microtissues. Cartilage microtissues were assembled from either 5000 human bone marrow-derived stromal cells (BMSC) or 5000 human articular chondrocytes (ACh) each using a customized microwell platform (the Microwell-mesh). Microtissues rapidly accumulate homogenous cartilage-like extracellular matrix (ECM), making them potentially useful building blocks for cartilage defect repair. Cartilage microtissues were cultured for 5 or 10 days and then cryopreserved in 90% serum plus 10% dimethylsulfoxide (DMSO) or commercial serum-free cryopreservation media. Cell viability was maximized during thawing by incremental dilution of serum to reduce oncotic shock, followed by washing and further culture in serum-free medium. When assessed with live/dead viability dyes, thawed microtissues demonstrated high viability but reduced immediate metabolic activity relative to unfrozen control microtissues. To further assess the functionality of the freeze-thawed microtissues, their capacity to amalgamate into a continuous tissue was assess over a 14 day culture. The amalgamation of microtissues cultured for 5 days was superior to those that had been cultured for 10 days. Critically, the capacity of cryopreserved microtissues to amalgamate into a continuous tissue in a subsequent 14-day culture was not compromised, suggesting that cryopreserved microtissues could amalgamate within a cartilage defect site. The quality ECM was superior when amalgamation was performed in a 2% O2 atmosphere than a 20% O2 atmosphere, suggesting that this process may benefit from the limited oxygen microenvironment within a joint. In summary, cryopreservation of cartilage microtissues is a viable option, and this manipulation can be performed without compromising tissue function. [ABSTRACT FROM AUTHOR]

For bone marrow stromal cells (BMSC) to be useful in cartilage repair their propensity for hypertrophic differentiation must be overcome. A single day of TGF-β1 stimulation activates intrinsic signaling cascades in BMSCs which subsequently drives both chondrogenic and hypertrophic differentiation. TGF-β1 stimulation upregulates SP7, a transcription factor known to contribute to hypertrophic differentiation, and SP7 remains upregulated even if TGF-β1 is subsequently withdrawn from the chondrogenic induction medium. Herein, we stably transduced BMSCs to express an shRNA designed to silence SP7, and assess the capacity of SP7 silencing to mitigate hypertrophy. SP7 silencing dampened both hypertrophic and chondrogenic differentiation processes, resulting in diminished microtissue size, impaired glycosaminoglycan production and reduced chondrogenic and hypertrophic gene expression. Thus, while hypertrophic features were dampened by SP7 silencing, chondrogenic differentation was also compromised. We further investigated the role of SP7 in monolayer osteogenic and adipogenic cultures, finding that SP7 silencing dampened characteristic mineralization and lipid vacuole formation, respectively. Overall, SP7 silencing affects the trilineage differentiation of BMSCs, but is insufficient to decouple BMSC hypertrophy from chondrogenesis. These data highlight the challenge of promoting BMSC chondrogenesis whilst simultaneously reducing hypertrophy in cartilage tissue engineering strategies. [ABSTRACT FROM AUTHOR]

Osteoarthritis is the most prevalent degenerative joint disease and one of the leading causes of physical impairment in the world's aging population. The human lifespan has significantly increased as a result of scientific and technological advancements. According to estimates, the world's elderly population will increase by 20% by 2050. Aging and age-related changes are discussed in this review in relation to the development of OA. We specifically discussed the cellular and molecular changes that occur in the chondrocytes during aging and how these changes may make synovial joints more susceptible to OA development. These changes include chondrocyte senescence, mitochondrial dysfunction, epigenetic modifications, and decreased growth factor response. The age-associated changes occur not only in the chondrocytes but also in the matrix, subchondral bone, and synovium. This review aims to provide an overview of the interplay between chondrocytes and matrix and how age-related changes affect the normal function of cartilage and contribute to OA development. Understanding the alterations that affect the function of chondrocytes will emerge new possibilities for prospective therapeutic options for the treatment of OA. [ABSTRACT FROM AUTHOR]

Minimally invasive surgery (MIS) offers several advantages to patients including minimum blood loss and quick recovery time. However, lack of tactile or haptic feedback and poor visualization of the surgical site often result in some unintentional tissue damage. Visualization aspects further limits the collection of imaged frame contextual details, therefore the utility of computational methods such as tracking of tissue and tools, scene segmentation, and depth estimation are of paramount interest. Here, we discuss an online preprocessing framework that overcomes routinely encountered visualization challenges associated with the MIS. We resolve three pivotal surgical scene reconstruction tasks in a single step; namely, (i) denoise, (ii) deblur, and (iii) color correction. Our proposed method provides a latent clean and sharp image in the standard RGB color space from its noisy, blurred, and raw inputs in a single preprocessing step (end-to-end in one step). The proposed approach is compared against current state-of-the-art methods that perform each of the image restoration tasks separately. Results from knee arthroscopy show that our method outperforms existing solutions in tackling high-level vision tasks at a significantly reduced computation time. [ABSTRACT FROM AUTHOR]

Background: The treatment for deep surgical site infection (SSI) following primary total hip arthroplasty (THA) varies internationally and it is at present unclear which treatment approaches are used in Australia. The aim of this study is to identify current treatment approaches in Queensland, Australia, show success rates and quantify the costs of different treatments.Methods: Data for patients undergoing primary THA and treatment for infection between January 2006 and December 2009 in Queensland hospitals were extracted from routinely used hospital databases. Records were linked with pathology information to confirm positive organisms. Diagnosis and treatment of infection was determined using ICD-10-AM and ACHI codes, respectively. Treatment costs were estimated based on AR-DRG cost accounting codes assigned to each patient hospital episode.Results: A total of n=114 patients with deep surgical site infection were identified. The majority of patients (74%) were first treated with debridement, antibiotics and implant retention (DAIR), which was successful in eradicating the infection in 60.3% of patients with an average cost of $13,187. The remaining first treatments were 1-stage revision, successful in 89.7% with average costs of $27,006, and 2-stage revisions, successful in 92.9% of cases with average costs of $42,772. Multiple treatments following 'failed DAIR' cost on average $29,560, for failed 1-stage revision were $24,357, for failed 2-stage revision were $70,381 and were $23,805 for excision arthroplasty.Conclusions: As treatment costs in Australia are high primary prevention is important and the economics of competing treatment choices should be carefully considered. These currently vary greatly across international settings. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence and predictors of physical activity, sedentary behaviour and fatigue five years after total knee replacement surgery. Design: A longitudinal cohort study. Setting: Community-dwelling adults who had previously undergone total knee replacement. Methods: Five-year follow-up questionnaire data were obtained from participants previously enrolled in a randomised controlled trial examining rehabilitation after total knee replacement. Main study outcomes at one year did not differ between randomisation groups, hence data were pooled for the present longitudinal analysis. Before and one and five years after surgery, participants completed questionnaires (Active Australia Survey, WOMAC, SF12 v2, demographics and fatigue). Results: 272/422 community-dwelling adults (45–74 years) completed the questionnaires at five years. Excessive sedentary behaviour was evident in 91% of the cohort, predicted by excessive sedentary behaviour and lack of energy at one year. Inadequate physical activity at five years was evident for 59% of the cohort, predicted by higher fatigue and comorbidity scores pre-surgery and inadequate physical activity at one year. Just under half (47%) of the cohort experienced clinically-important fatigue at five years, predicted by clinically-important fatigue before and one year after surgery, lack of sleep before surgery and physical activity one year after surgery. Conclusion: Documenting physical activity, sedentary behaviour and fatigue before and one year after knee replacement is important to identify those at risk of longer-term inadequate physical activity, excessive sedentary behaviour and clinically-important fatigue. Interventions to maintain activity and reduce sedentary behaviour are needed to reap the potential health benefits of total knee replacement surgery. [ABSTRACT FROM AUTHOR]

The anatomy of the osteochondral junction is complex because several tissue components exist as a unit, including uncalcified cartilage (with superficial, middle, and deep layers), calcified cartilage, and subchondral bone. Furthermore, it is difficult to study because this region is made up of a variety of cell types and extracellular matrix compositions. Using X-ray fluorescence microscopy, we present a protocol for simultaneous elemental detection on fresh frozen samples. We transferred the osteochondral sample using a tape-assisted system and successfully tested it in synchrotron X-ray fluorescence. This protocol elucidates the distinct distribution of elements at the human knee's osteochondral junction, making it a useful tool for analyzing the co-distribution of various elements in both healthy and diseased states. [ABSTRACT FROM AUTHOR]

Objective: Reconstruction of acetabular defects has been extremely challenging in both primary and revision total hip arthroplasty (THA). Impaction bone grafting (IBG) can restore the acetabulum bone mass and anatomically reconstruct the acetabulum. Our study aimed to report the short and medium‐term clinical and radiographic outcomes of IBG for acetabular reconstruction in the cemented THA in the Chinese population. Methods: This was a single‐center retrospective review enrolling 57 patients between May 2013 and July 2019. The patients with acetabular defects were treated with IBG, using low dose irradiated freeze‐dried allograft bone with or without autograft bone, in the cemented THA performed by one senior surgeon. Harris hip score (HHS), standard pelvis anterior–posterior radiograph and lateral hip radiograph were obtained before operation and at 1 week, 3 months, 12 months, and yearly. Graft osteointegration was evaluated by Oswestry's criteria, and complication was documented at the last follow‐up. Independent sample ANOVA test and Pearson chi‐square tests are used for statistical analysis. Results: There were 61 hips in 57 patients. The average follow‐up time was 35.59 months (5–77 months). According to AAOS classification, a total of 18 hips were identified as segmental bone deficiency (type I), with 21 and 22 hips for cavitary bone deficiency (type II) and the combined bone deficiency (type III), respectively. The average HHS was improved from 44.49 (range: 32–58) preoperatively to 86.98 (range: 78–93) postoperatively. Graft osteointegration was satisfactory (Oswestry score ≥2) in all patients. No dislocation occurred in the 57 patients (61 hips) during follow‐up. Although one cup migrated, no revision, re‐revision, radiographic loosening, graft bone lysis, or postoperative complications were detected at the final follow‐up. Conclusions: IBG with low‐dose irradiated freeze‐dried allograft bone in acetabular bone defect reconstruction is a reliable technique for restoring acetabular bone defects in THA. [ABSTRACT FROM AUTHOR]

Background: It is well-known that both macrophages and osteocytes are critical regulators of osteogenesis and osteoclastogenesis, yet there is limited understanding of the macrophage-osteocyte interaction, and how their crosstalk could affect bone homeostasis and mineralization. This research therefore aims to investigate the effects of macrophage polarization on osteocyte maturation and mineralization process. Methods: A macrophage-derived conditioned medium based osteocyte culture was set up to investigate the impact of macrophages on osteocyte maturation and terminal mineralization. Surgically induced osteoarthritis (OA) rat model was used to further investigate the macrophage-osteocyte interaction in inflammatory bone remodeling, as well as the involvement of the Notch signaling pathway in the mineralization process. Results: Our results identified that osteocytes were confined in an immature stage after the M1 macrophage stimulation, showing a more rounded morphology, higher expression of early osteocyte marker E11, and significantly lower expression of mature osteocyte marker DMP1. Immature osteocytes were also found in inflammatory bone remodeling areas, showing altered morphology and mineralized structures similar to those observed under the stimulation of M1 macrophages in vitro, suggesting that M1 macrophages negatively affect osteocyte maturation, leading to abnormal mineralization. The Notch signaling pathway was found to be down regulated in M1 macrophage-stimulated osteocytes as well as osteocytes in inflammatory bone. Overexpression of the Notch signaling pathway in osteocytes showed a significant circumvention on the negative effects from M1 macrophage. Conclusion: Taken together, our findings provide valuable insights into the mechanisms involved in abnormal bone mineralization under inflammatory conditions. [ABSTRACT FROM AUTHOR]

Osteoblast lineage cells are direct effectors of osteogenesis and are, therefore, commonly used to evaluate the in vitro osteogenic capacity of bone substitute materials. This method has served its purposes when testing novel bone biomaterials; however, inconsistent results between in vitro and in vivo studies suggest the mechanisms that govern a material's capacity to mediate osteogenesis are not well understood. The emerging field of osteoimmunology and immunomodulation has informed a paradigm shift in our view of bone biomaterials–from one of an inert to an osteoimmunomodulatory material–highlighting the importance of immune cells in materials-mediated osteogenesis. Neglecting the importance of the immune response during this process is a major shortcoming of the current evaluation protocol. In this study we evaluated a potential angiogenic bone substitute material cobalt incorporated with β-tricalcium phosphate (CCP), comparing the traditional “one cell type” approach with a “multiple cell types” approach to assess osteogenesis, the latter including the use of immune cells. We found that CCP extract by itself was sufficient to enhance osteogenic differentiation of bone marrow stem cells (BMSCs), whereas this effect was cancelled out when macrophages were involved. In response to CCP, the macrophage phenotype switched to the M1 extreme, releasing pro-inflammatory cytokines and bone catabolic factors. When the CCP materials were implanted into a rat femur condyle defect model, there was a significant increase of inflammatory markers and bone destruction, coupled with fibrous encapsulation rather than new bone formation. These findings demonstrated that the inclusion of immune cells (macrophages) in the in vitro assessment matched the in vivo tissue response, and that this method provides a more accurate indication of the essential role of immune cells when assessing materials-stimulated osteogenesis in vitro . [ABSTRACT FROM AUTHOR]

The calcified cartilage zone (CCZ) is a thin interlayer between the hyaline articular cartilage and the subchondral bone and plays an important role in maintaining the joint homeostasis by providing biological and mechanical support from unmineralized cartilage to the underlying mineralized subchondral bone. The hallmark of CCZ characteristics in osteoarthritis (OA) is less well known. The aim of our study is to evaluate the structural, molecular, and biochemical composition of CCZ in tissues affected by primary knee OA and its relationship with disease severity. We collected osteochondral tissue samples stratified according to disease severity, from 16 knee OA patients who underwent knee replacement surgery. We also used meniscectomy‐induced rat samples to confirm the pathophysiologic changes of human samples. We defined the characteristics of the calcified cartilage layer using a combination of morphological, biochemical, proteomic analyses on laser micro‐dissected tissue. Our results demonstrated that the Calcium/Phosphate ratio is unchanged during the OA progression, but the calcium‐binding protein and cadherin binding protein, as well as carbohydrate metabolism‐related proteins, undergo significant changes. These changes were further accompanied by thinning of the CCZ, loss of collagen and proteoglycan content, the occurrence of the endochondral ossification, neovasculature, loss of the elastic module, loss of the collagen direction, and increase of the tortuosity indicating an altered structural and mechanical properties of the CCZ in OA. In conclusion, our results suggest that the calcified cartilage changes can reflect the disease progression. [ABSTRACT FROM AUTHOR]

Background Magnetic resonance imaging ( MRI) is being increasingly utilized to define pathology and guide treatment in patients presenting with wrist pain. The clinical relevance of MRI identified or confirmed pathology has not been established, and the prevalence of asymptomatic MRI pathology is not known. Methods Twenty volunteers with no previous wrist injury or symptoms underwent bilateral MRI wrist studies in this exploratory diagnostic study. The scans were reported by an experienced musculoskeletal radiologist and an experienced wrist surgeon, with a consensus reached on each report. Results There were 3.15 positive MRI findings per wrist. There were 126 positive findings (range 1-6 per wrist). Sixty-eight ganglia were identified. Eleven ligament tears or perforations were also identified. Increased joint fluid was seen at many sites, most frequently adjacent to the piso-triquetral joint. Conclusion The accuracy of MRI in identifying triangular fibrocartilage complex tears, intercarpal ligament tears and carpal bone osteonecrosis is rapidly being refined. Positive MRI findings are common and may be coincidental in patients with wrist pain. MRI findings need to be correlated closely with clinical examination and history. [ABSTRACT FROM AUTHOR]

When repairing cartilage defects a major challenge is achieving high-quality integration between the repair tissue and adjacent native cartilage. Matrix-rich cartilage is not easily remodeled, motivating several studies to trial enzyme treatment of the tissue interface to facilitate remodeling and integration. Studying and optimizing such processes is tedious, as well as potentially expensive, and thus simpler models are needed to evaluate the merits of enzyme treatment on cartilage tissue integration. Herein, we used engineered cartilage microtissues formed from bone marrow-derived stromal cells (BMSC) or expanded articular chondrocytes (ACh) to study the impact of enzyme treatment on cartilage tissue integration and matrix remodeling. A 5-min treatment with collagenase appeared to improve cartilage microtissue integration, while up to 48 h treatment with hyaluronidase did not. Alcian blue and anti-collagen II staining suggested that collagenase treatment did facilitate near seamless integration of cartilage microtissues. Microtissue sections were stained with Picrosirius red and characterized using polarized light microscopy, revealing that individual microtissues contained a collagen network organized in concentric shells. While collagenase treatment appeared to improve tissue integration, assessment of the collagen fibers with polarized light indicated that enzymatically damaged networks were not remodeled nor restored during subsequent culture. This model and these data paradoxically suggest that collagen network disruption is required to improve cartilage tissue integration, but that the disrupted collagen networks are unlikely to subsequently be restored. Future studies should attempt to limit collagen network disruption to the surface of the cartilage, and we recommend using Picrosirius red staining and polarized light to assess the quality of matrix remodeling and integration. [ABSTRACT FROM AUTHOR]

When repairing cartilage defects a major challenge is achieving high-quality integration between the repair tissue and adjacent native cartilage. Matrix-rich cartilage is not easily remodeled, motivating several studies to trial enzyme treatment of the tissue interface to facilitate remodeling and integration. Studying and optimizing such processes is tedious, as well as potentially expensive, and thus simpler models are needed to evaluate the merits of enzyme treatment on cartilage tissue integration. Herein, we used engineered cartilage microtissues formed from bone marrowderived stromal cells (BMSC) or expanded articular chondrocytes (ACh) to study the impact of enzyme treatment on cartilage tissue integration and matrix remodeling. A 5-min treatment with collagenase appeared to improve cartilage microtissue integration, while up to 48 h treatment with hyaluronidase did not. Alcian blue and anti-collagen II staining suggested that collagenase treatment did facilitate near seamless integration of cartilage microtissues. Microtissue sections were stained with Picrosirius red and characterized using polarized light microscopy, revealing that individual microtissues contained a collagen network organized in concentric shells. While collagenase treatment appeared to improve tissue integration, assessment of the collagen fibers with polarized light indicated that enzymatically damaged networks were not remodeled nor restored during subsequent culture. This model and these data paradoxically suggest that collagen network disruption is required to improve cartilage tissue integration, but that the disrupted collagen networks are unlikely to subsequently be restored. Future studies should attempt to limit collagen network disruption to the surface of the cartilage, and we recommend using Picrosirius red staining and polarized light to assess the quality of matrix remodeling and integration. [ABSTRACT FROM AUTHOR]

Abstract: Determining the properties and integrity of subchondral bone in the developmental stages of osteoarthritis, especially in a form that can facilitate real-time characterization for diagnostic and decision-making purposes, is still a matter for research and development. This paper presents relationships between near infrared absorption spectra and properties of subchondral bone obtained from 3 models of osteoarthritic degeneration induced in laboratory rats via: (i) menisectomy (MSX); (ii) anterior cruciate ligament transaction (ACL); and (iii) intra-articular injection of mono-ido-acetate (1mg) (MIA), in the right knee joint, with 12 rats per model group (N=36). After 8weeks, the animals were sacrificed and knee joints were collected. A custom-made diffuse reflectance NIR probe of diameter 5mm was placed on the tibial surface and spectral data were acquired from each specimen in the wavenumber range 4000–12500cm−1. After spectral acquisition, micro computed tomography (micro-CT) was performed on the samples and subchondral bone parameters namely: bone volume (BV) and bone mineral density (BMD) were extracted from the micro-CT data. Statistical correlation was then conducted between these parameters and regions of the near infrared spectra using multivariate techniques including principal component analysis (PCA), discriminant analysis (DA), and partial least squares (PLS) regression. Statistically significant linear correlations were found between the near infrared absorption spectra and subchondral bone BMD (R2 =98.84%) and BV (R2 =97.87%). In conclusion, near infrared spectroscopic probing can be used to detect, qualify and quantify changes in the composition of the subchondral bone, and could potentially assist in distinguishing healthy from OA bone as demonstrated with our laboratory rat models. [Copyright &y& Elsevier]

Regenerative medicine-based approaches for the repair of damaged cartilage rely on the ability to propagate cells while promoting their chondrogenic potential. Thus, conditions for cell expansion should be optimized through careful environmental control. Appropriate oxygen tension and cell expansion substrates and controllable bioreactor systems are probably critical for expansion and subsequent tissue formation during chondrogenic differentiation. We therefore evaluated the effects of oxygen and microcarrier culture on the expansion and subsequent differentiation of human osteoarthritic chondrocytes. Freshly isolated chondrocytes were expanded on tissue culture plastic or CultiSpher-G microcarriers under hypoxic or normoxic conditions (5% or 20% oxygen partial pressure, respectively) followed by cell phenotype analysis with flow cytometry. Cells were redifferentiated in micromass pellet cultures over 4 weeks, under either hypoxia or normoxia. Chondrocytes cultured on tissue culture plastic proliferated faster, expressed higher levels of cell surface markers CD44 and CD105 and demonstrated stronger staining for proteoglycans and collagen type II in pellet cultures compared with microcarrier-cultivated cells. Pellet wet weight, glycosaminoglycan content and expression of chondrogenic genes were significantly increased in cells differentiated under hypoxia. Hypoxia-inducible factor-3α mRNA was up-regulated in these cultures in response to low oxygen tension. These data confirm the beneficial influence of reduced oxygen on ex vivo chondrogenesis. However, hypoxia during cell expansion and microcarrier bioreactor culture does not enhance intrinsic chondrogenic potential. Further improvements in cell culture conditions are therefore required before chondrocytes from osteoarthritic and aged patients can become a useful cell source for cartilage regeneration. [ABSTRACT FROM AUTHOR]

This article investigates in vitro the hypothesis that the frequency profile of ultrasound reflections may be used to characterize degradation and osteoarthritic progression in articular cartilage, irrespective of the effects of transducer orientation. To this end, ultrasound echoes were taken in the time domain from the articular surface and osteochondral junction of normal, collagen meshwork-disrupted, proteoglycan-depleted, and osteoarthritic samples, converted to the frequency domain by fast Fourier transform and analyzed. Our results show the significant effects of specific enzymatic degradation programs on the ultrasound frequency profile of reflections from the cartilage surface and osteochondral junction, and their manifestation in the tissue surrounding a focal osteoarthritic defect. Collagen meshwork disruption was most apparent in the profile of reflections from the articular surface, while proteoglycan depletion was most clearly observed in the reflections from the osteochondral junction. The reflected signals from the osteochondral junction may further contain information about the subchondral bone. From these results we proposed that the analysis of specific frequencies of reflected ultrasound signals has the potential to differentiate normal from degraded articular cartilage-on-bone, when the angle of incidence can be controlled within a ±1.2° limit. This encourages further research into the effects of progressive artificial degradation of the cartilage matrix and subchondral bone on the spectral profile to quantify the relationship between the frequency profile and the level of specific degradation in naturally degraded joints. [ABSTRACT FROM AUTHOR]

In view of the controversy of the clinical use of hyperbaric oxygen (HBO) treatment to stimulate fracture healing and bone regeneration, we have analyzed the effects of daily exposure to HBO on the proliferation and differentiation of human osteoblasts in vitro. HBO stimulated proliferation when osteoblasts were cultured in 10% fetal calf serum (FCS), whereas an inhibitory effect of HBO was observed when cultures were supplemented with 2% FCS. On the other hand, HBO enhanced biomineralization with an increase in bone nodule formation, calcium deposition, and alkaline phosphatase activity, whereas no cytotoxic effect was detected using a lactate dehydrogenase activity assay. The data suggest that the exposure of osteoblasts to HBO enhances differentiation toward the osteogenic phenotype, providing cellular evidence of the potential application of HBO in fracture healing and bone regeneration. [ABSTRACT FROM AUTHOR]

Should mechanical VTE prophylaxis be indicated in all Asian patients who are contraindica... Recommendation Yes, mechanical VTE prophylaxis is the most appropriate VTE prevention in Asian patients who are contraindicated for pharmacological prophylaxis. This study, on 454 patients who underwent hip fracture surgery with mechanical prophylaxis in all cases, showed an overall DVT incidence of 6.4% (29 patients) and a PE incidence of 1.3% (6 patients) [[24]]. Should a mechanical device for VTE prophylaxis be routinely applied in Asian patients unde... Recommendation Yes, a mechanical device for VTE prophylaxis should routinely be applied in all Asian patients undergoing knee and hip arthroplasty and hip fracture surgery. The subgroup analysis found that 19 (0.8%) proximal DVTs and 83 (3.8%) distal DVTs developed in the patients without chemoprophylaxis, and 4 (0.7%) proximal DVTs and 28 (5.2%) distal DVTs developed in the patients with chemoprophylaxis [[18]]. [Extracted from the article]

Literature can be useful in co-designing healthcare when transformed into a accessible and creative format. This study explores how a card tool developed from literature (Health Experience Insight Cards) can be used in healthcare co-design. The card tool was used in a pilot co-design workshop with six participants (Male=3, Female=3). Group A included people with only professional experience and Group B included people with a combination of personal and professional experience with diabetes. Both groups used the cards, in a storytelling activity to explore the patient experience. Interaction analysis identified three types of interaction that resulted from the storytelling activity: (a) applying the insight from the card to the character/story, (b) discussing real life and (c) discussing experiences. Differences in interactions were found between the two groups. An empathetic dialogue between stakeholders was developed by the group with only professional experience. Experience sharing was triggered between the group with professional and personal experience. The Health Experience Insight Cards offer a useful way to communicate insights from existing literature for use in co-designing health experiences. In our pilot study, the cards triggered discussion, enabled participants in the co-design workshop to discuss the health experience literature, related real-life issues and people's experiences. [ABSTRACT FROM AUTHOR]

Bone, a mineralized tissue, continuously undergoes remodeling. It is a process that engages the mineralization and demineralization of the bone matrix, orchestrated by the interactions among cells and cell-secreted biomolecules under the bone ionic microenvironment (BIE). The osteoinductive properties of the demineralized organic bone matrix and many biological factors have been well-investigated. However, the impact of the bone ionic environment on cell differentiation and osteogenesis remains largely unknown. In this study, we extracted and isolated inorganic bone components (bone-derived monetite, BM) using a low-temperature method and, for the first time, investigated whether the BIE could actively affect cell differentiation and regulate osteoimmune reactions. It was evidenced that the BIE could foster the osteogenesis of human bone marrow stromal cells (hBMSCs) and promote hBMSCs mineralization without using osteogenic inductive agents. Interestingly, it was noted that BIE resulted in intracellular mineralization, evidenced by intracellular accumulation of carbonate hydroxyapatite similar to that oberved in osteoblasts cultured in osteoinductive media. Additionally, BIE was found to enhance osteogenesis by generating a favorable osteoimmune environment. In a rat calvarial bone defect model, the osteogenic capacity of BIE was evaluated using a collagen type I-impregnated BM (Col-BM) composite. It showed that Col-BM significantly promoted new bone formation in the critical-size bone defect areas. Taken together, this is the first study that investigated the influence of the BIE on osteogenesis, osteoimmunology, and in situ bone tissue engineering. The innate osteoinductive potential of inorganic bone components, both in vitro and in vivo , not only expands the understanding of the BIE on osteogenesis but also benefits future biomaterials engineering for bone tissue regeneration. [Display omitted] • A biomimetic ionic environment is generated from bone monetite for the first time. • The bone ionic environment (BIE) promotes osteogenic differentiation. • A favorable osteoimmunomodulatory role of BIE is identified for osteogenesis. • Regenerative capacity of BIE brings new insights in bone biomaterials design. [ABSTRACT FROM AUTHOR]

Virtually all bone marrow-derived stromal cell (BMSC) chondrogenic induction cultures include greater than 2 weeks exposure to transforming growth factor-β (TGF-β), but fail to generate cartilage-like tissue suitable for joint repair. Herein we used a micro-pellet model (5 × 103 BMSC each) to determine the duration of TGF-β1 exposure required to initiate differentiation machinery, and to characterize the role of intrinsic programming. We found that a single day of TGF-β1 exposure was sufficient to trigger BMSC chondrogenic differentiation and tissue formation, similar to 21 days of TGF-β1 exposure. Despite cessation of TGF-β1 exposure following 24 hours, intrinsic programming mediated further chondrogenic and hypertrophic BMSC differentiation. These important behaviors are obfuscated by diffusion gradients and heterogeneity in commonly used macro-pellet models (2 × 105 BMSC each). Use of more homogenous micro-pellet models will enable identification of the critical differentiation cues required, likely in the first 24-hours, to generate high quality cartilage-like tissue from BMSC. Futrega et al. challenge the long established chondrogenic differentiation protocol used to induce bone marrow-derived stromal cell (BMSC) differentiation which presumes the need for more than 2 weeks of continuous TGF-β1 exposure. Using a micro-pellet model, they show that BMSC differentiation is triggered by a single day of TGF-β1 exposure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

With the rising cases of diabetes, more people are living with the complexity of this condition and calling for innovation and harmonisation of lifestyles, healthcare, technology and policy. This study explores the tension of this experience as a starting point to support the development of experience-focussed innovations for people living with diabetes. Existing experience literature was analysed through the previously designed Health Experience Insight Cards: Living with Diabetes Edition, previously developed by the authors. The cards were inductively sorted by the research team to understand the tensions within this experience. Five dimensions of tension were identified; (a) Person as expert and Doctor as expert, (b) Cost and benefit, (c) Medical ideals and Life priorities, (d) Quality of support and Quantity of support and (e) Stability and the Need for change. This research contributes to the field of health design through providing an exemplar of how in-depth research on a health experience can be collated, framed, presented as a tension tool and used in health experience design to embrace the complexity of living with diabetes. The tensions and the tool can be used by designers, health professionals, service providers and policymakers to evaluate and identify opportunities for experienced-centred health innovation. [ABSTRACT FROM AUTHOR]

Backgrounds: The ASA (American Society of Anaesthesiologists) Score is the current standard for measuring comorbidity in the Australian Hip Fracture registry, however it has never been validated for this purpose. Subsequently, a more appropriate and useful measure should be investigated. This study aimed to compare the ASA and Charlson Comorbidity Index (CCI) scores in predicting 12-month mortality following acute hip fracture.Methods: A retrospective analysis was performed on an audit database of patients who were admitted to an orthogeriatric unit in a public metropolitan hospital from November 2010 to October 2011. 12-month mortality data was linked through a dual search of Queensland Health and mortality registry data. The Charlson comorbidity index was retrospectively applied. Demographics (age, gender, admission residence) and covariates including ASA, CCI, fracture type, fixation type, cognitive impairment on admission, BMI and time to surgery were analysed with logistic regression. ROC curve analysis was performed to assess varying thresholds for each comorbidity system.Results: A total of 320 patients were available for audit. Unadjusted bivariate analysis demonstrated significant difference between groups regarding increased age (p = 0.004), ASA score (p<0.001), CCI (p = 0.002), age-adjusted CCI (p = 0.002) and admission from a care facility (p<0.001). Logistic regression analysis demonstrated that only ASA (p<0.001) and admission from a care facility (p<0.001, OR=3.36, 95% CI = 1.9 - 6.0) independently predicted 12-month mortality; CCI was not a significant predictor in any models (p = 0.827, age-adjusted CCI: p = 0.864). Using ROC analysis, the ASA (AUC=0.668) outperformed either CCI (AUC=0.607 (CCI), AUC=0.614 (CCI age-adjusted).Conclusions: The ASA score is independently associated with 12-month mortality; this was not replicated using either version of the CCI. The data does not suggest using the CCI in registry level datasets for the purposes of predicting 12-month mortality. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to apply bibliometric tools to Australian and New Zealand orthopaedic publications produced between 2008 and 2018 to identify the most highly cited publications, author and institution collaboration networks and topic trends. Analysis of the literature can highlight areas of emerging interest and knowledge gaps, and direct future research.Methods: A systematic search was conducted using Clarivate Analytics Web of Science. Citation analysis was carried out using Web of Science. Collaboration networks were constructed using chord diagrams. Trends in publication topics were analysed using simple linear regression to find the rate of change of publication volume on each topic.Results: A total of 3097 publications contributed to by 8855 individual authors met inclusion criteria. Across the study period, there was a large increase in the annual volume of publications on the topic of ACL (Anterior Cruciate Ligament) surgery. We also found that collaboration between Australian and New Zealand authors was very low with only 1% (n = 31) of publications including authors from both countries and 0.4% (n = 12) including orthopaedic surgeons or trainees from both.Conclusions: Publications on ACL surgery have increased over the past decade, likely due to the presence of competing surgical approaches and the recently recognized risk of osteoarthritis following ACL reconstruction. The overall collaboration between Australian and New Zealand authors was very low which lends itself to opportunities for future research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]