Amplified detection of SARS-COV-2 B.1.1.529 (Omicron) gene oligonucleotides based on exonuclease III-aided MoS2 /AIE nanoprobes.

The coronavirus disease-2019 pandemic reflects the underdevelopment of point-of-care diagnostic technology. Nuclei acid (NA) detection is the "gold standard" method for the early diagnosis of the B.1.1.529 (Omicron) variant of severe acute respiratory syndrome-coronavirus disease-2. Polymerase chain reaction is the main method for NA detection but requires considerable manpower and sample processing taking ≥ 3 h. To simplify the operation processes and reduce the detection time, exonuclease III (Exo III)-aided MoS2 /AIE nanoprobes were developed for rapid and sensitive detection of the oligonucleotides of Omicron. Molybdenum disulfide (MoS2 ) nanosheets with excellent optical absorbance and distinguishable affinity to single-strand and duplex DNAs were applied as quenchers, and aggregation-induced emission (AIE) molecules with high luminous efficiency were designed as donor in fluorescence resonance energy transfer-based nanoprobes. Exo III with catalytic capability was used for signal amplification to increase the sensitivity of detection. The composite nanoprobes detected the mutated nucleocapsid (N)-gene and spike (S)-gene oligonucleotides of Omicron within 40 min with a limit of detection of 4.7 pM, and showed great potential for application in community medicine.

Nanomanipulation of Ligand Nanogeometry Modulates Integrin/Clathrin-Mediated Adhesion and Endocytosis of Stem Cells.

Nanosubstrate engineering can be a biomechanical approach for modulating stem cell differentiation in tissue engineering. However, the study of the effect of clathrin-mediated processes on manipulating this behavior is unexplored. Herein, we develop integrin-binding nanosubstrates with confined nanogeometries that regulate clathrin-mediated adhesion- or endocytosis-active signaling pathways for modulating stem fates. Isotropically presenting ligands on the nanoscale enhances the expression of clathrin in cells, thereby facilitating uptake of dexamethasone-loaded nanoparticles (NPs) to boost osteogenesis of stem cells. In contrast, anisotropic ligand nanogeometry suppresses this clathrin-mediated NP entry by strengthening the association between clathrin and adhesion spots to reinforce mechanotransduced signaling, which can be abrogated by the pharmacological inhibition of clathrin. Meanwhile, inhibiting focal adhesion formation hinders cell spreading and enables a higher endocytosis efficiency. Our findings reveal the crucial roles of clathrin in both endocytosis and mechanotransduction of stem cells and provide the parameter of ligand nanogeometry for the rational design of biomaterials for tissue engineering.

COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives.

COVID-19 is a trending topic worldwide due to its immense impact on society. Recent trends have shifted from acute effects towards the long-term morbidity of COVID-19. In this review, we hypothesize that SARS-CoV-2 contributes to age-related perturbations in endothelial and adipose tissue, which are known to characterize the early aging process. This would explain the long-lasting symptoms of SARS-CoV-2 as the result of an accelerated aging process. Connective tissues such as adipose tissue and musculoskeletal tissue are the primary sites of aging. Therefore, current literature was analyzed focusing on the musculoskeletal symptoms in COVID-19 patients. Hypovitaminosis D, increased fragility, and calcium deficiency point towards bone aging, while joint and muscle pain are typical for joint and muscle aging, respectively. These characteristics could be classified as early osteoarthritis-like phenotype. Exploration of the impact of SARS-CoV-2 and osteoarthritis on endothelial and adipose tissue, as well as neuronal function, showed similar perturbations. At a molecular level, this could be attributed to the angiotensin-converting enzyme 2 expression, renin-angiotensin system dysfunction, and inflammation. Finally, the influence of the nicotinic cholinergic system is being evaluated as a new treatment strategy. This is combined with the current knowledge of musculoskeletal aging to pave the road towards the treatment of long-term COVID-19.

Osteocyte Dysfunction in Joint Homeostasis and Osteoarthritis.

Structural disturbances of the subchondral bone are a hallmark of osteoarthritis (OA), including sclerotic changes, cystic lesions, and osteophyte formation. Osteocytes act as mechanosensory units for the micro-cracks in response to mechanical loading. Once stimulated, osteocytes initiate the reparative process by recruiting bone-resorbing cells and bone-forming cells to maintain bone homeostasis. Osteocyte-expressed sclerostin is known as a negative regulator of bone formation through Wnt signaling and the RANKL pathway. In this review, we will summarize current understandings of osteocytes at the crossroad of allometry and mechanobiology to exploit the relationship between osteocyte morphology and function in the context of joint aging and osteoarthritis. We also aimed to summarize the osteocyte dysfunction and its link with structural and functional disturbances of the osteoarthritic subchondral bone at the molecular level. Compared with normal bones, the osteoarthritic subchondral bone is characterized by a higher bone volume fraction, a larger trabecular bone number in the load-bearing region, and an increase in thickness of pre-existing trabeculae. This may relate to the aberrant expressions of sclerostin, periostin, dentin matrix protein 1, matrix extracellular phosphoglycoprotein, insulin-like growth factor 1, and transforming growth factor-beta, among others. The number of osteocyte lacunae embedded in OA bone is also significantly higher, yet the volume of individual lacuna is relatively smaller, which could suggest abnormal metabolism in association with allometry. The remarkably lower percentage of sclerostin-positive osteocytes, together with clustering of Runx-2 positive pre-osteoblasts, may suggest altered regulation of osteoblast differentiation and osteoblast-osteocyte transformation affected by both signaling molecules and the extracellular matrix. Aberrant osteocyte morphology and function, along with anomalies in molecular signaling mechanisms, might explain in part, if not all, the pre-osteoblast clustering and the uncoupled bone remodeling in OA subchondral bone.

Extracellular Calcium Ion Concentration Regulates Chondrocyte Elastic Modulus and Adhesion Behavior.

Extracellular calcium ion concentration levels increase in human osteoarthritic (OA) joints and contribute to OA pathogenesis. Given the fact that OA is a mechanical problem, the effect of the extracellular calcium level ([Ca2+]) on the mechanical behavior of primary human OA chondrocytes remains to be elucidated. Here, we measured the elastic modulus and cell-ECM adhesion forces of human primary chondrocytes with atomic force microscopy (AFM) at different extracellular calcium ion concentration ([Ca2+]) levels. With the [Ca2+] level increasing from the normal baseline level, the elastic modulus of chondrocytes showed a trend of an increase and a subsequent decrease at the level of [Ca2+], reaching 2.75 mM. The maximum increment of the elastic modulus of chondrocytes is a 37% increase at the peak point. The maximum unbinding force of cell-ECM adhesion increased by up to 72% at the peak point relative to the baseline level. qPCR and immunofluorescence also indicated that dose-dependent changes in the expression of myosin and integrin ß1 due to the elevated [Ca2+] may be responsible for the variations in cell stiffness and cell-ECM adhesion. Scratch assay showed that the chondrocyte migration ability was modulated by cell stiffness and cell-ECM adhesion: as chondrocyte's elastic modulus and cell-ECM adhesion force increased, the migration speed of chondrocytes decreased. Taken together, our results showed that [Ca2+] could regulate chondrocytes stiffness and cell-ECM adhesion, and consequently, influence cell migration, which is critical in cartilage repair.

An ultrasensitive and selective fluorescent nanosensor based on porphyrinic metal-organic framework nanoparticles for Cu2+ detection.

Detecting trace amounts of copper ions (Cu2+) is of high importance since copper is an essential element in the environment and the human body. Despite the recent advances in Cu2+ detection, the current approaches still suffer from insensitivity and lack of in situ detection in living cells. In the present work, a fluorescent nanosensor based on porphyrinic metal-organic framework nanoparticles (MOF-525 NPs) is proposed for sensitive and selective monitoring of Cu2+ in aqueous solution and living cells. The MOF-525 NPs with attractive properties, including ultrasmall size, good water dispersity and intense red fluorescence, are prepared via a facile and environment-friendly hydrothermal route. The fluorescence signal of MOF-525 NPs could be quenched statically by Cu2+ with high selectivity due to the strong affinity of Cu2+ to the porphyrin ligand in MOF-525. The proposed fluorescent nanosensor has a linear response in the range of 1.0-250 nM with a low detection limit of 220 pM. Furthermore, it is successfully employed for the detection of Cu2+ in water samples and the intracellular imaging of Cu2+ in living cells, demonstrating its great potential in the sensing and biological fields.

Adaptive Fusion of Deep Learning With Statistical Anatomical Knowledge for Robust Patella Segmentation From CT Images.

Kneeosteoarthritis (KOA), as a leading joint disease, can be decided by examining the shapes of patella to spot potential abnormal variations. To assist doctors in the diagnosis of KOA, a robust automatic patella segmentation method is highly demanded in clinical practice. Deep learning methods, especially convolutional neural networks (CNNs) have been widely applied to medical image segmentation in recent years. Nevertheless, poor image quality and limited data still impose challenges to segmentation via CNNs. On the other hand, statistical shape models (SSMs) can generate shape priors which give anatomically reliable segmentation to varying instances. Thus, in this work, we propose an adaptive fusion framework, explicitly combining deep neural networks and anatomical knowledge from SSM for robust patella segmentation. Our adaptive fusion framework will accordingly adjust the weight of segmentation candidates in fusion based on their segmentation performance. We also propose a voxel-wise refinement strategy to make the segmentation of CNNs more anatomically correct. Extensive experiments and thorough assessment have been conducted on various mainstream CNN backbones for patella segmentation in low-data regimes, which demonstrate that our framework can be flexibly attached to a CNN model, significantly improving its performance when labeled training data are limited and input image data are of poor quality.

Radiomics signature of osteoarthritis: Current status and perspective.

Osteoarthritis (OA) is one of the fast-growing disability-related diseases worldwide, which has significantly affected the quality of patients' lives and brings about substantial socioeconomic burdens in medical expenditure. There is currently no cure for OA once the bone damage is established. Unfortunately, the existing radiological examination is limited to grading the disease's severity and is insufficient to precisely diagnose OA, detect early OA or predict OA progression. Therefore, there is a pressing need to develop novel approaches in medical image analysis to detect subtle changes for identifying early OA development and rapid progressors. Recently, radiomics has emerged as a unique approach to extracting high-dimensional imaging features that quantitatively characterise visible or hidden information from routine medical images. Radiomics data mining via machine learning has empowered precise diagnoses and prognoses of disease, mainly in oncology. Mounting evidence has shown its great potential in aiding the diagnosis and contributing to the study of musculoskeletal diseases. This paper will summarise the current development of radiomics at the crossroads between engineering and medicine and discuss the application and perspectives of radiomics analysis for OA diagnosis and prognosis. The translational potential of this article: Radiomics is a novel approach used in oncology, and it may also play an essential role in the diagnosis and prognosis of OA. By transforming medical images from qualitative interpretation to quantitative data, radiomics could be the solution for precise early OA detection, progression tracking, and treatment efficacy prediction. Since the application of radiomics in OA is still in the early stages and primarily focuses on fundamental studies, this review may inspire more explorations and bring more promising diagnoses, prognoses, and management results of OA.

Radiomics analysis of patellofemoral joint improves knee replacement risk prediction: Data from the Multicenter Osteoarthritis Study (MOST).

Objective: Knee replacement (KR) is the last-resort treatment for knee osteoarthritis. Although radiographic evidence of tibiofemoral joint has been widely adopted for prognostication, patellofemoral joint has gained little attention and may hold additional value for further improvements. We aimed to quantitatively analyse patellofemoral joint through radiomics analysis of lateral view radiographs for improved KR risk prediction. Design: From the Multicenter Osteoarthritis Study dataset, we retrospectively retrieved the initial-visit lateral left knee radiographs of 2943 patients aged 50 to 79. They were split into training and test cohorts at a 2:1 ratio. A comprehensive set of radiomic features were extracted within the best-performing subregion of patellofemoral joint and combined into a radiomics score (RadScore). A KR risk score, derived from Kellgren-Lawrence grade (KLG) of tibiofemoral joint and RadScore of patellofemoral joint, was developed by multivariate Cox regression and assessed using time-dependent area under receiver operating characteristic curve (AUC). Results: While patellofemoral osteoarthritis (PFOA) was insignificant during multivariate analysis, RadScore was identified as an independent risk factor (multivariate Cox p-value < 0.001) for KR. The subgroup analysis revealed that RadScore was particularly effective in predicting rapid progressor (KR occurrence before 30 months) among early- (KLG < 2) and mid-stage (KLG â€‹= â€‹2) patients. Combining two joints radiographic information, the AUC reached 0.89/0.87 for predicting 60-month KR occurrence. Conclusions: The RadScore of the patellofemoral joint on lateral radiographs emerges as an independent prognostic factor for improving KR prognosis prediction. The KR risk score could be instrumental in managing progressive knee osteoarthritis interventions.

Engineering an extracellular matrix-functionalized, load-bearing tendon substitute for effective repair of large-to-massive tendon defects.

A significant clinical challenge in large-to-massive rotator cuff tendon injuries is the need for sustaining high mechanical demands despite limited tissue regeneration, which often results in clinical repair failure with high retear rates and long-term functional deficiencies. To address this, an innovative tendon substitute named "BioTenoForce" is engineered, which uses (i) tendon extracellular matrix (tECM)'s rich biocomplexity for tendon-specific regeneration and (ii) a mechanically robust, slow degradation polyurethane elastomer to mimic native tendon's physical attributes for sustaining long-term shoulder movement. Comprehensive assessments revealed outstanding performance of BioTenoForce, characterized by robust core-shell interfacial bonding, human rotator cuff tendon-like mechanical properties, excellent suture retention, biocompatibility, and tendon differentiation of human adipose-derived stem cells. Importantly, BioTenoForce, when used as an interpositional tendon substitute, demonstrated successful integration with regenerative tissue, exhibiting remarkable efficacy in repairing large-to-massive tendon injuries in two animal models. Noteworthy outcomes include durable repair and sustained functionality with no observed breakage/rupture, accelerated recovery of rat gait performance, and >1 cm rabbit tendon regeneration with native tendon-like biomechanical attributes. The regenerated tissues showed tendon-like, wavy, aligned matrix structure, which starkly contrasts with the typical disorganized scar tissue observed after tendon injury, and was strongly correlated with tissue stiffness. Our simple yet versatile approach offers a dual-pronged, broadly applicable strategy that overcomes the limitations of poor regeneration and stringent biomechanical requirements, particularly essential for substantial defects in tendon and other load-bearing tissues.

Subchondral bone expansion in advanced knee osteoarthritis: Relation with radiographic severity and role in surgical decision-making.

Background: Joint space width (JSW) is a traditional imaging marker for knee osteoarthritis (OA) severity, but it lacks sensitivity in advanced cases. We propose tibial subchondral bone area (TSBA), a new CT imaging marker to explore its relationship with OA radiographic severity, and to test its performance for classifying surgical decisions between unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) compared to JSW. Methods: We collected clinical, radiograph, and CT data from 182 patients who underwent primary knee arthroplasty (73 UKA, 109 TKA). The radiographic severity was scored using Kellgren-Lawrence (KL) grading system. TSBA and JSW were extracted from 3D CT-reconstruction model. We used independent t-test to investigate the relationship between TSBA and KL grade, and binary logistic regression to identify factors associated with TKA risk. The accuracy of TSBA, JSW and established classification model in differentiating between UKA and TKA was assessed using AUC. Results: All parameters exhibited inter- and intra-class coefficients greater than 0.966. Patients with KL grade 4 had significantly larger TSBA than those with KL grade 3. TSBA (0.708 of AUC) was superior to minimal/average JSW (0.547/0.554 of AUC) associated with the risk of receiving TKA. Medial TSBA, together with gender and Knee Society Knee Score, emerged as independent classification factors in multivariate analysis. The overall AUC of composite model for surgical decision-making was 0.822. Conclusion: Tibial subchondral bone area is an independent imaging marker for radiographic severity, and is superior to JSW for surgical decision-making between UKA and TKA in advanced OA patients.

SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids.

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages' role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

Engineered biochemical cues of regenerative biomaterials to enhance endogenous stem/progenitor cells (ESPCs)-mediated articular cartilage repair.

As a highly specialized shock-absorbing connective tissue, articular cartilage (AC) has very limited self-repair capacity after traumatic injuries, posing a heavy socioeconomic burden. Common clinical therapies for small- to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies, including microfracture, mosaicplasty, autologous chondrocyte implantation (ACI), and matrix-induced ACI (MACI). However, these treatments frequently result in mechanically inferior fibrocartilage, low cost-effectiveness, donor site morbidity, and short-term durability. It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC. Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments. A deeper understanding of the mechanism of endogenous cartilage healing is furthering the (bio)design and application of these scaffolds. Currently, the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells (ESPCs) presents an evolving improvement for cartilage repair. This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration. Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed. The recent advances in novel (bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs (e.g. adhesion, migration, proliferation, differentiation, matrix production, and remodeling) for cartilage repair are summarized. Finally, this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.

Adapting a Clinical Practice Guideline for Management of Patients with Knee and Hip Osteoarthritis by Hong Kong Physiotherapists.

Knee and hip osteoarthritis are common disabling conditions globally. Although numerous international clinical practice guidelines exist to guide physiotherapy management, not all recommendations issued from these guidelines can be translated to other contexts without considering the cultural acceptability and clinical implementability of targeted countries. Because the ADAPTE framework provides a robust methodology to adapt guidelines to the local context, this study used its methodology to adapt high-quality guideline recommendations to promote optimal physiotherapy care for knee and hip osteoarthritis in Hong Kong. The ADAPTE framework was used and modified to complete the adaptation process. International clinical practice guidelines were identified from eight guideline clearinghouses and six electronic databases. Two independent reviewers critically appraised the eligible guidelines using the AGREE II tool. We extracted and tabulated recommendations from high-quality guidelines. A voting-based consensus among interdisciplinary experts was conducted to decide on suitable recommendations for the Hong Kong context and whether there was a need to modify them. Pertinent recommendations were then translated into the traditional Chinese language. Our team members suggested modifying four tools and adding one to explore the patient's feedback on the recommendations, to the ADAPTE framework. The adaptation was performed on three high-quality guidelines. We adapted 28 and 20 recommendations for treating knee and hip osteoarthritis, respectively. We recommend a multimodal treatment for managing knee and hip osteoarthritis. Land- and aquatic-based exercises, patient education, and self-management were strongly recommended for patients with knee osteoarthritis. Land- and aquatic-based exercises were strongly recommended for patients with hip osteoarthritis. This is the first adaptation study in Hong Kong. It provides guidance to local physiotherapists on managing patients with knee and hip osteoarthritis. Future studies should test the effectiveness of implementing this adapted guideline to improve local physiotherapy care in Hong Kong.

Light on osteoarthritic joint: from bench to bed.

Osteoarthritis (OA) is one of the rapidly growing disability-associated conditions with population aging worldwide. There is a pressing need for precise diagnosis and timely intervention for OA in the early stage. Current clinical imaging modalities, including pain radiography, magnetic resonance imaging, ultrasound, and optical coherent tomography, are limited to provide structural changes when the damage has been established or advanced. It prompts further endeavors in search of novel functional and molecular imaging, which potentially enables early diagnosis and intervention of OA. A hybrid imaging modality based on photothermal effects, photoacoustic imaging, has drawn wide attention in recent years and has seen a variety of biomedical applications, due to its great performance in yielding high-contrast and high-resolution images from structure to function, from tissue down to molecular levels, from animals to human subjects. Photoacoustic imaging has witnessed gratifying potentials and preliminary effects in OA diagnosis. Regarding the treatment of OA, photothermal-triggered therapy has exhibited its attractions for enhanced therapeutic outcomes. In this narrative review, we will discuss photoacoustic imaging for the diagnosis and monitoring of OA at different stages. Structural, functional, and molecular parameter changes associated with OA joints captured by photoacoustics will be summarized, forming the diagnosis perspective of the review. Photothermal therapy applications related to OA will also be discussed herein. Lastly, relevant clinical applications and its potential solutions to extend photoacoustic imaging to deeper OA situations have been proposed. Although some aspects may not be covered, this mini review provides a better understanding of the diagnosis and treatment of OA with exciting innovations based on tissue photothermal effects. It may also inspire more explorations in the field towards earlier and better theranostics of OA.

Association between hypertension and osteoarthritis: A systematic review and meta-analysis of observational studies.

Objective: Literature examining the relationship between elevated blood pressure and osteoarthritis (OA) has yielded conflicting results. This study aimed to systematically review the relationship between hypertension and OA in both load-bearing and non-load-bearing joints. Methods: A systematic literature search was performed on Embase, Emcare, MEDLINE and Ovid Nursing Database. The associations between hypertension and OA development in knees, hips and hands were analysed by calculating the odds ratio (OR). Results: A total of 26 studies with 97,960 participants were included. The overall odds of having OA significantly increased in the people with hypertension compared to the normotensive ones (OR â€‹= â€‹1.60, 95%CI â€‹= â€‹1.33, 1.94). The association of hypertension with OA was detected in knee (OR â€‹= â€‹1.62, 95%CI â€‹= â€‹1.32, 1.98), not in hand (OR â€‹= â€‹1.19, 95%CI â€‹= â€‹0.92, 1.53). Moreover, there existed a stronger association of hypertension with radiographic knee OA (OR â€‹= â€‹1.89, 95%CI â€‹= â€‹1.40, 2.54) than symptomatic knee OA (OR â€‹= â€‹1.39, 95%CI â€‹= â€‹1.17, 1.65). The association between hypertension and radiographic knee OA remained statistically significant for the studies that adjusted for body mass index (BMI) (OR â€‹= â€‹1.42, 95%CI â€‹= â€‹1.13, 1.78), and was particularly strong in women (OR â€‹= â€‹2.27, 95%CI â€‹= â€‹1.17, 4.39). Conclusion: A BMI-independent association between hypertension and radiographic knee OA existed with potential sex variation, which warrants further investigations into the underlying genetic, hormonal and environmental factors.The translational potential of this article: Blood pressure has been reported to link with OA for years ago, however, its contribution to OA is still unclear and conflicted in different reports. This review indicated an intimate relationship between hypertension and structural damages of knee OA, rather than simply chronic joint pain, especially in women. This finding not only provides stronger support for further investigations into the causal risk factor, i.e. hypertension, of OA from tissue level to molecular level, but also putting forward a novel thinking in OA pathogenesis and its therapy strategies. Orthopedic translation: This study further strengthen the association between hypertension and radiographic knee OA. It points in a vascular aetiology hypothesis of OA. It might open up a new avenue for repositioning anti-hypertensive medications for osteoarthritis treatment.

Hemodynamic stress shapes subchondral bone in osteoarthritis: An emerging hypothesis.

Osteoarthritis (OA) is no longer regarded as a simple wear-and-tear problem of articular cartilage. Instead, OA is a whole joint disorder involving both cartilaginous and non-cartilaginous tissues such as subchondral bone and synovium. Among them, subchondral bone undergoes constant remodeling in response to the changes of mechanical environment. Current understanding of subchondral bone disturbance in OA is limited to its link with an altered local mechanical loading as a result of ligament or meniscus injury. Very recently, hypertension, the most common vascular morbidity, has been emerged as an independent risk factor of OA. It might suggest a plausible role of systemic hemodynamic mechanical stress in subchondral bone remodeling and the pathogenesis of OA. However, their relationship remains not fully understood. Based on our preliminary clinical observation on the association of hemodynamic parameters with subchondral bone mass and microstructure in late-stage knee OA patients, we formulate a vascular etiology hypothesis of OA from a mechanobiology perspective. Noteworthily, hemodynamic stress associated with subchondral bone mineral density; yet compressive mechanical loading does not. Furthermore, hemodynamic parameters positively correlated with subchondral plate-like trabecular bone volume but negatively associated with rod-like trabecular bone volume. In contrast, compressive mechanical loading tends to increase both plate-like and rod-like trabecular bone volume. Taken together, it warrants further investigations into the distinct role of hemodynamic or compressive stress in shaping subchondral bone in the pathophysiology of OA. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This work provides a new insight, from the angle of biomechanics, into the emerging role of vascular pathologies, such as hypertension, in the pathogenesis of OA. It might open up a new avenue for the development of a mechanism-based discovery of novel diagnostics and therapeutics.

Emerging microfluidics-enabled platforms for osteoarthritis management: from benchtop to bedside.

Osteoarthritis (OA) is a prevalent debilitating age-related joint degenerative disease. It is a leading cause of pain and functional disability in older adults. Unfortunately, there is no cure for OA once the damage is established. Therefore, it promotes an urgent need for early detection and intervention of OA. Theranostics, combining therapy and diagnosis, emerges as a promising approach for OA management. However, OA theranostics is still in its infancy. Three fundamental needs have to be firstly fulfilled: i) a reliable OA model for disease pathogenesis investigation and drug screening, ii) an effective and precise diagnostic platform, and iii) an advanced fabrication approach for drug delivery and therapy. Meanwhile, microfluidics emerges as a versatile technology to address each of the needs and eventually boost the development of OA theranostics. Therefore, this review focuses on the applications of microfluidics, from benchtop to bedside, for OA modelling and drug screening, early diagnosis, and clinical therapy. We first introduce the basic pathophysiology of OA and point out the major unfilled research gaps in current OA management including lack of disease modelling and drug screening platforms, early diagnostic modalities and disease-modifying drugs and delivery approaches. Accordingly, we then summarize the state-of-the-art microfluidics technology for OA management from in vitro modelling and diagnosis to therapy. Given the existing promising results, we further discuss the future development of microfluidic platforms towards clinical translation at the crossroad of engineering and biomedicine.

Mechanistic links between systemic hypertension and open angle glaucoma.

Systemic hypertension or hypertension is a very common chronic age-related disease worldwide. It is typically characterised by a sustained elevation of blood pressure, particularly when the systolic blood pressure and/or diastolic blood pressure are of more than 140 mmHg and 90 mmHg, respectively. If hypertension is not well controlled, it may lead to an increased risk of stroke and heart attack. It has been shown that hypertension is linked to various ocular diseases, including cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma. Glaucoma is the leading cause of irreversible blindness worldwide. Primary open angle glaucoma is the most common form of the disease and is usually characterised by an increase in intraocular pressure. This condition, together with normal tension glaucoma, constitutes open angle glaucoma. Systemic hypertension has been identified as a risk factor for open angle glaucoma. It is speculated that blood pressure is involved in the pathogenesis of open angle glaucoma by altering intraocular pressure or ocular blood flow, or both. Recent evidence has shown that both extremely high and low blood pressure are associated with increased risk of open angle glaucoma. Additional pathogenic mechanisms, including increased inflammation likely to be involved in the development and progression of these two diseases, are discussed.