Cardamonin inhibits osteogenic differentiation by downregulating Wnt/beta-catenin signaling and alleviates subchondral osteosclerosis in osteoarthritic mice.

Osteoarthritis (OA) is a common degenerative joint disease, and subchondral osteosclerosis is an important pathological change that occurs in its late stages. Cardamonin (CD) is a natural flavonoid isolated from Alpinia katsumadai that has anti-inflammatory activity. The objectives of this study were to investigate the therapeutic effects and potential mechanism of CD in regulating OA subchondral osteosclerosis at in vivo and in vitro settings. Eight-week-old male C57BL/6J mice were randomly divided into four groups: sham operation, anterior cruciate ligament transection (ACLT)-induced OA model, low-dose and high-dose CD treated ACLT-OA model groups. Histological assessment and immunohistochemical examinations for chondrocyte metabolism-related markers metalloproteinase-13, ADAMTS-4, Col II, and Sox-9 were performed. Microcomputed tomography was used to assess the sclerosis indicators in subchondral bone. Further, MC3T3-E1 (a mouse calvarial preosteoblast cell line) cells were treated with various concentrations of CD to reveal the influence and potential molecular pathways of CD in osteogenic differentiations. Animal studies suggested that CD alleviated the pathological changes in OA mice such as maintaining integrity and increasing the thickness of hyaline cartilage, decreasing the thickness of calcified cartilage, decreasing the Osteoarthritis Research Society International score, regulating articular cartilage metabolism, and inhibiting subchondral osteosclerosis. In vitro investigation indicated that CD inhibited alkaline phosphatase expression and production of calcium nodules during osteogenic differentiation of MC3T3-E1 cells. In addition, CD inhibited the expression of osteogenic differentiation-related indicators and Wnt/ß-catenin pathway-related proteins. In conclusion, CD inhibits osteogenic differentiation by downregulating Wnt/ß-catenin signaling and alleviating subchondral osteosclerosis in a mouse model of OA.

Fabrication, Characterization, and In Vitro Cytotoxicity Assessment of Tri-Layered Multifunctional Scaffold for Effective Chronic Wound Healing.

Chronic wounds have been a global health risk that demands intensive exploration. A tri-layered biomaterial scaffold has been developed for skin wounds. The top layer of the scaffold is superhydrophobic, and the bottom layer is hydrophilic, both of which were electrospun using recycled expanded polystyrene (EPS) and monofilament fishing line (MFL), respectively. The intermediate layer of the scaffold comprised hydrogel by cross-linking chitosan (CS) with polyethylene glycol. The surface morphology, surface chemistry, thermal degradation, and wettability characteristics of each layer of the scaffold were examined. Also, the antibacterial activity and in vitro cytotoxicity study on the combined tri-layered scaffold were assessed against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Data revealed exceptional water repellency of the heat-treated electrospun top superhydrophobic layer (TSL) with a high-water contact angle (WCA) of 172.44°. A TSL with 15 wt% of micro-/nano-inclusions had the best thermal stability above 400 °C. The bottom hydrophilic layer (BHL) displayed a WCA of 9.91°. Therapeutically, the synergistic effect of the combined tri-layered scaffold significantly inhibited bacteria growth by 70.5% for E. coli and 68.6% for S. aureus. Furthermore, cell viability is enhanced when PEG is included as part of the intermediate CS hydrogel layer (ICHL) composition.

Movement Artifact Suppression in Wearable Low-Density and Dry EEG Recordings Using Active Electrodes and Artifact Subspace Reconstruction.

Wearable low-density dry electroencephalogram (EEG) headsets facilitate multidisciplinary applications of brain-activity decoding and brain-triggered interaction for healthy people in real-world scenarios. However, movement artifacts pose a great challenge to their validity in users with naturalistic behaviors (i.e., without highly controlled settings in a laboratory). High-precision, high-density EEG instruments commonly embed an active electrode infrastructure and/or incorporate an auxiliary artifact subspace reconstruction (ASR) pipeline to handle movement artifact interferences. Existing endeavors motivate this study to explore the efficacy of both hardware and software solutions in low-density and dry EEG recordings against non-tethered settings, which are rarely found in the literature. Therefore, this study employed a LEGO-like electrode-holder assembly grid to coordinate three 3-channel system designs (with passive/active dry vs. passive wet electrodes). It also conducted a simultaneous EEG recording while performing an oddball task during treadmill walking, with speeds of 1 and 2 KPH. The quantitative metrics of pre-stimulus noise, signal-to-noise ratio, and inter-subject correlation from the collected event-related potentials of 18 subjects were assessed. Results indicate that while treating a passive-wet system as benchmark, only the active-electrode design more or less rectified movement artifacts for dry electrodes, whereas the ASR pipeline was substantially compromised by limited electrodes. These findings suggest that a lightweight, minimally obtrusive dry EEG headset should at least equip an active-electrode infrastructure to withstand realistic movement artifacts for potentially sustaining its validity and applicability in real-world scenarios.

Coronoid Fracture Reconstruction with Ipsilateral Olecranon Osteoarticular Autograft in the Acute Setting: A Case Report.

CASE: An 18-year-old male polytrauma patient sustained a high-energy posterior fracture dislocation of his left elbow associated with a comminuted and irreparable O'Driscoll type 2 subtype 3 anteromedial facet coronoid fracture. He underwent early coronoid reconstruction using ipsilateral olecranon osteoarticular autograft with incorporation of the sublime tubercle attachment of the medial collateral ligament and repair of the lateral ulnar collateral ligament. A 3-year follow-up revealed a functional, painless, congruent, and stable elbow. CONCLUSION: Early reconstruction of a highly comminuted coronoid fracture may be a useful salvage option for the polytrauma patient, thereby avoiding complications associated with late reconstruction of posttraumatic elbow instability.

Higenamine Promotes Osteogenesis Via IQGAP1/SMAD4 Signaling Pathway and Prevents Age- and Estrogen-Dependent Bone Loss in Mice.

Osteoporosis is a common bone disease caused by an imbalance of bone resorption and formation that results in a loss of total bone density. SMAD2/3 signal transduction is known to play a crucial role in osteogenic differentiation through transforming growth factor-beta (TGF-ß). By screening a library of small-molecule compounds, the current study identifies higenamine (HG) as an active osteogenic agent that could be a therapeutic candidate for osteoporosis. In vitro data demonstrated that HG effectively induced expressions of osteogenic markers in mouse bone marrow stromal cell (BMSCs) and preosteoblastic cell cultures. Further, HG treatment resulted in enhanced bone formation and prevented accelerated bone loss on two animal models that mimic spontaneous senile osteoporosis and postmenopausal osteoporosis. IQ motif-containing GTPase-activating protein 1 (IQGAP1) was confirmed as a novel target of HG, where HG appears to bind to the Glu-1019 site of IQGAP1 to exert its osteogenic effects. Data subsequently suggested that HG promoted phosphorylation of SMAD2/3 and regulated the SMAD2/3 pathway by inhibiting SMAD4 ubiquitination. Overall, the findings highlight HG as a new small-molecule drug to promote bone formation through SMAD2/3 pathway in osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR).

The Role of IL-6 and TMEM100 in Lumbar Discogenic Pain and the Mechanism of the Glycine-Serine-Threonine Metabolic Axis: A Metabolomic and Molecular Biology Study.

Background: It is well established that discogenic low back pain (DLBP) is often caused by the inflammatory response during intervertebral disc degeneration (IDD). However, it remains unclear how inflammatory mediators such as Interleukin-6 (IL-6) are involved in discogenic pain caused by degeneration and intervertebral disc (IVD) metabolism. The purpose of this study is to study the relationship between IL-6 and Transmembrane protein 100 (TMEM100), and to analyze the different metabolites and metabolic pathways in various rat intervertebral discs by metabonomics. Methods: We established a rat model of IDD-DLBP by disc punctures and PBS infusion to examine the rat pain behaviors. Intervertebral disc tissues were harvested for molecular biology experiments to explore the relationship between IL-6 and TMEM100. High-resolution mass spectrometry (HRMS) was performed for untargeted metabolomics, and nuclear magnetic resonance spectroscopy metabolomics (MRS) for differential metabolites and metabolic pathways. Results: The results showed a significant decrease in vonFrey test, hot plate test and acetone test (P < 0.05). The expression of IL-6 and TMEM100 in DLBP model was significantly higher than that in sham control group and IDD discs without PBS infusion group (P < 0.05). There were 15 major contributing metabolites identified in the DLBP intervertebral discs through metabolomic studies, involving 6 major metabolic pathways. The main differential metabolites included nitric oxide (NO), ammonia, and lactic acid as the metabolic endpoints; and the differential metabolic pathways included the glycine-serine-threonine (Gly-Ser-Thr), which is gradually weakened with the progression of inflammation. Conclusion: The change of TMEM100 expression mediated by il-6 is related to the Gly-Ser-Thr metabolic axis and plays an important role in the relief of discogenic pain.

DEPDC1 as a crucial factor in the progression of human osteosarcoma.

OBJECTIVE: Novel therapeutic strategies are emerging with the increased understanding of the underlying mechanisms of human osteosarcoma. This current study tends to decipher the potentially critical role of DEP domain-containing 1 (DEPDC1), a tumor-related gene, during the progression of osteosarcoma. METHODS: Bioinformatics analysis of 25,035 genes from the National Center for Biotechnology Information (NCBI) databases was performed to screen differentially expressed genes between osteosarcoma and normal control groups, complemented by the examination of 85 clinical osteosarcoma specimens. Furthermore, the manipulation of DEPDC1 expression levels by using silencing RNA (siRNA) or lentiviral vector intervention on human osteosarcoma cells was performed to reveal its role and interactions in in vitro and in vivo settings. RESULTS: Gene expression profile analysis and immunohistochemical (IHC) examination suggested that DEPDC1 is highly expressed in human osteosarcoma cells and tumor tissue. The silencing of DEPDC1 arrested osteosarcoma cell proliferation, promoted apoptosis, and ceased tumor metastasis. Studies involving clinical human osteosarcoma cases exhibited a strong correlation of DEPDC1 over-expressed osteosarcoma specimens with a reduced patient survival rate. CONCLUSIONS: Collectively, this study demonstrated that DEPDC1 is a critical driver in the promotion of osteosarcoma progression and results in poor patient prognosis. Genetically targeting or pharmacologically inhibiting DEPDC1 may serve as a promising strategy for treating human osteosarcoma.

Synthesis and Properties of Magnetic Fe3O4/PCL Porous Biocomposite Scaffolds with Different Sizes and Quantities of Fe3O4 Particles.

In clinical practice, to treat diseases such as osteosarcoma or chondrosarcoma with broad surgical ostectomy, it would be ideal to have scaffolds that not only fill up the bone void but also possess the ability to regulate the subsequent regimes for targeted chemotherapy and/or bone regeneration. Magnetic targeting of therapeutic agents to specific sites in the body provides certain advantages such as minimal side-effects of anti-cancer drugs. The objective of this study was to characterize novel magnetic scaffolds that can be used as a central station to regulate the drug delivery of a magnetic nanoparticle system. Different sizes and quantities of Fe3O4 particles were mixed with poly-ε-caprolactone (PCL) to construct the magnetic scaffolds, and their mechanical properties, degradation performance, and cell biocompatibility were evaluated. It appeared that the presence of Fe3O4 particles influenced the magnetic, mechanical, and biological performances of the scaffolds. The prepared bio-nanocomposite scaffolds provided predominantly magnetic/superparamagnetic properties. Scaffolds with a micron-sized Fe3O4 to PCL weight (wt) ratio of 0.1:0.9 exhibited higher mechanical performances among samples, with Young's modulus reaching 1 MPa and stiffness, 13 N/mm. Although an increased Fe3O4 particle proportion mildly influenced cell growth during the biocompatibility test, none of the Fe3O4/PCL scaffolds showed a cytotoxic effect.

Polymeric biomaterials for wound healing applications: a comprehensive review.

Chronic wounds have been a global health threat over the past few decades, requiring urgent medical and research attention. The factors delaying the wound-healing process include obesity, stress, microbial infection, aging, edema, inadequate nutrition, poor oxygenation, diabetes, and implant complications. Biomaterials are being developed and fabricated to accelerate the healing of chronic wounds, including hydrogels, nanofibrous, composite, foam, spongy, bilayered, and trilayered scaffolds. Some recent advances in biomaterials development for healing both chronic and acute wounds are extensively compiled here. In addition, various properties of biomaterials for wound-healing applications and how they affect their performance are reviewed. Based on the recent literature, trilayered constructs appear to be a convincing candidate for the healing of chronic wounds and complete skin regeneration because they mimic the full thickness of skin: epidermis, dermis, and the hypodermis. This type of scaffold provides a dense superficial layer, a bioactive middle layer, and a porous lower layer to aid the wound-healing process. The hydrophilicity of scaffolds aids cell attachment, cell proliferation, and protein adhesion. Other scaffold characteristics such as porosity, biodegradability, mechanical properties, and gas permeability help with cell accommodation, proliferation, migration, differentiation, and the release of bioactive factors.

Classification and Treatment for Cervical Spine Fracture with Ankylosing Spondylitis: A Clinical Nomogram Prediction Study.

Objective: Through the follow-up analysis of cervical spine fracture cases with ankylosing spondylitis (AS), a treatment-oriented fracture classification method is introduced to evaluate the clinical efficacy guided by this classification method. Method: A retrospective analysis was performed on 128 AS patients who underwent comprehensive treatment in the Spine Surgery Department of Qingdao University Hospital from January 2009 to May 2018. Statistics of patient demographic data, distribution of different fractures corresponding to surgical methods, 3-year follow-up outcomes, and summary of objective fracture classification methods were analyzed. A prospective 5-year follow-up study of 90 patients with AS cervical spine fractures from June 2015 to August 2020 was also included. Statistical differences on the distribution of factors such as case information, cervical spine sagittal sequence parameters, and fracture classification were assessed. Correlations between surgical information, American Spinal Injuries Association grade (ASIA), modified Japanese Orthopaedic Association scores (mJOA), and other factors were analyzed to establish a nomogram predictive model for curative effect outcomes. Overall, three major types and the four subtypes of AS cervical spine fractures were evaluated based on the clinical efficacy of the classification and the selection of surgical treatment methods. Result: The most common type of fracture was type II (30 cases, 33.33%), most of the subtypes were A (37 cases), followed by B (36 cases) and C (17 cases). Twenty-four of 28 patients with type I underwent anterior surgery, and 47 of 62 patients with type II and III underwent posterior surgery. The average follow-up time was 25.76 ± 11.80 months. The results of predicting clinical variables are different but include factors such as fracture type and subtype, type of operation, and age. The predictor variables include the above-mentioned similar variables, but survival is more affected by the fracture type of the patient. Conclusion: This predictive model based on follow-up information delineation points out the impact of ankylosing spondylitis cervical spine fracture classification on surgical selection and clinical efficacy.

Identification and coregulation pattern analysis of long noncoding RNAs following subacute spinal cord injury.

Long noncoding RNAs (lncRNAs) have been demonstrated to play critical regulatory roles in posttranscriptional and transcriptional regulation in eukaryotic cells. However, the characteristics of many lncRNAs, particularly their expression patterns in the lesion epicenter of spinal tissues following subacute spinal cord injury (SCI), remain unclear. In this study, we determined the expression profiles of lncRNAs in the lesion epicenter of spinal tissues after traumatic SCI and predicted latent regulatory networks. Standard Allen's drop surgery was conducted on mice, and hematoxylin and eosin staining was used to observe the damaged area. High-throughput sequencing was performed to identify the differential expression profiles of lncRNAs. Quantitative real-time polymerase chain reaction was conducted to evaluate the quality of the sequencing results. Bioinformatics analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, coexpression analysis, and protein-protein interaction analysis, were performed. Targeted binding of lncRNA-miRNA-mRNA was predicted by TargetScan and miRanda. A total of 230 differentially expressed lncRNAs were identified and preliminarily verified, and some potential regulatory networks were constructed. These findings improve our understanding of the mechanisms underlying subacute SCI; differentially expressed lncRNAs are closely involved in pathophysiological processes by regulating multiple pathways. Further studies are essential for revealing the exact mechanism underlying competing endogenous RNA pathways in vivo and in vitro.

Human Peripheral Nerve-Derived Pluripotent Cells Can Be Stimulated by In Vitro Bone Morphogenetic Protein-2.

We have recently identified a population of cells within the peripheral nerves of adult rodent animals (mice and rats) that can respond to Bone Morphogenetic Protein-2 (BMP-2) exposure or physical injury to rapidly proliferate. More importantly, these cells exhibited embryonic differentiation potentials that could be induced into osteoblastic and endothelial cells in vitro. The current study examined human nerve specimens to compare and characterize the cells after BMP-2 stimulation. Fresh pieces of human nerve tissue were minced and treated with either BMP-2 (750 ng/mL) or a PBS vehicle for 12 h at 37 °C, before being digested in 0.2% collagenase and 0.05% trypsin-EDTA. Isolated cells were cultured in a restrictive stem cell medium. Significantly more cells were obtained from the nerve pieces with the BMP-2 treatment in comparison with the PBS vehicle controls. Cell colonies started to form at Day 3. Expressions of the four transcription factors, namely, Klf4, c-Myc, Sox2, and Oct4, were confirmed at both the transcriptional and translational levels. The cells can be maintained in the stem cell culture medium for at least 6 weeks without changing their morphology. When the cells were transferred to a fibroblast growth medium, dispersed spindle-shaped motile cells were noted and became fibroblast activated protein-α (FAP) positive with immunocytochemistry staining. The data suggest that human peripheral nerve tissue also contains a population of cells that can respond to BMP-2 and express Klf4, Sox2, cMyc, and Oct4-the four transcription factors driving cell pluripotency. These cells are able to differentiate into FAP-positive fibroblasts. In summary, in human peripheral nerves also reside a population of quiescent cells with pluripotency potential that may be the same cells as rodent nerve-derived adult stem (NEDAPS) cells. It is proposed that these cells are possibly at the core of a previously unknown natural mechanism for healing an injury.

Effects of Hypoxia on Proliferation and Apoptosis of Osteosarcoma Cells.

BACKGROUND: Hypoxia can happen during solid tumor growth including osteosarcoma. This study investigated the relationship of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) on osteosarcoma cell growth and apoptosis under hypoxic conditions. MATERIALS AND METHODS: Human osteosarcoma cells were cultured under normal or hypoxic conditions. Inhibitors of HIF-1α and VEGF were applied to the cells separately or in combination to block the respective proteins. Cell proliferation and apoptosis were examined by MTT and TUNEL assays, and real-time PCR and ELISA were performed for mRNA and protein expression. RESULTS: There was a dramatic decrease of cell proliferation and an elevation of apoptosis under hypoxia. Blockage of HIF-1α and VEGFR enhanced the cell growth retardation and promoted apoptotic changes. Moreover, blockage of HIF-1α significantly eliminated the expression of VEGF in the cell culture media, and vice versa. CONCLUSION: HIF-1α and VEGF work closely in regulating osteosarcoma cell growth under hypoxic conditions and blockage of either of them may subsequently influence the presence of the other.

Glycine-Serine-Threonine Metabolic Axis Delays Intervertebral Disc Degeneration through Antioxidant Effects: An Imaging and Metabonomics Study.

Although intervertebral disc degeneration (IDD) can be described as different stages of change through biological methods, this long and complex process cannot be defined in stages by single or simple combination of biological techniques. Under the background of the development of nuclear magnetic resonance (NMR) technology and the emerging metabonomics, we based on animal models and expanded to the study of clinical human degeneration models. The characteristics of different stages of IDD were analyzed by omics. Omics imaging combined with histology, cytology, and proteomics was used for screening of the intervertebral disc (IVD) of research subjects. Furthermore, mass spectrometry nontargeted metabolomics was used to explore profile of metabolites at different stages of the IDD process, to determine differential metabolic pathways and metabolites. NMR spectroscopy was used to qualitatively and quantitatively identify markers of degeneration. NMR was combined with mass spectrometry metabolomics to explore metabolic pathways. Metabolic pathways were determined through protein molecular biology and histocytology of the different groups. Distinguishing advantages of magnetic resonance spectroscopy (MRS) for analysis of metabolites and effective reflection of structural integrity and water molecule metabolism through diffusion tensor imaging (DTI) were further used to verify the macrometabolism profile during degeneration. A corresponding model of in vitro metabolomics and in vivo omics imaging was established. The findings of this study show that a series of metabolic pathways associated with the glycine-serine-threonine (Gly-Ser-Thr) metabolic axis affects carbohydrate patterns and energy utilization efficiency and ultimately delays disc degeneration through antioxidant effects.

Exosomal MATN3 of Urine-Derived Stem Cells Ameliorates Intervertebral Disc Degeneration by Antisenescence Effects and Promotes NPC Proliferation and ECM Synthesis by Activating TGF-ß.

OBJECTIVE: Low back pain (LBP) is one of the top three causes of disability in developed countries, and intervertebral disc degeneration (IDD) is a major contributor to LBP. In the process of IDD, there is a gradual decrease in nucleus pulposus cells (NPCs) and extracellular matrix (ECM). Exosomes are important exocrine mediators of stem cells that can act directly on cells for tissue repair and regeneration. In this study, we determined the antisenescence, cell proliferation promotion, and ECM modulation effects of human urine-derived stem cell (USC) exosomes (USC-exos) on degenerated intervertebral discs and explored the underlying mechanism. METHODS AND MATERIALS: USCs were identified by multipotent differentiation and flow cytometry for mesenchymal stem cell- (MSC-) specific surface protein markers. USC-exos were isolated from the conditioned medium of USCs by ultracentrifugation and then analyzed by transmission electron microscopy (TEM), particle size analysis, and western blotting (WB) for exosome marker proteins. The effects of USC-exos on NPC proliferation and ECM synthesis were assessed by Cell Counting Kit-8 (CCK-8), WB, and immunofluorescence (IF) analyses. The protein differences between normal and degenerative intervertebral discs were mined, and the temporal and spatial variations in matrilin-3 (MATN3) content were determined by WB and IF in the intervertebral disc tissues. The candidate molecules that mediated the function of USC-exos were screened out and confirmed by multiple assays. Meanwhile, the mechanism underlying the candidate protein in USC-exos-induced cell proliferation and regulation of ECM synthesis promoting the activities of NPCs was explored. In addition, the effects of USC-exos on ameliorating intervertebral disc degeneration (IVD) in mice were examined by assessing computed tomography (CT), magnetic resonance imaging (MRI), and histological analyses. RESULTS: The flow cytometry results showed that USCs were positive for CD29, CD44, and CD73, which are USC surface-specific markers, but negative for CD34 and CD45. In addition, USCs showed osteogenic, adipogenic, and chondrogenic differentiation potential. USC-exos exhibited a cup-shaped morphology, with a mean diameter of 49.7 ± 7.3 nm, and were positive for CD63 and TSG101 and negative for calnexin. USC-exos could promote NPC proliferation and ECM synthesis. The protein content of the matrilin family was significantly reduced in degenerative intervertebral discs, and the decrease in MATN3 was the most significant. USC-exos were found to be rich in MATN3 protein, and exosomal MATN3 was required for USC-exos-induced promotion of NPC proliferation and ECM synthesis, as well as alleviation of intervertebral disc degeneration in IVD rats. In addition, the effects of MATN3 in USC-exos were demonstrated to be achieved by activating TGF-ß, which elevated the phosphorylation level of SMAD and AKT. CONCLUSIONS: Our study suggests that reduced MATN3 can be considered a characteristic of intervertebral disc degeneration. USC-exos may represent a potentially effective agent for alleviating intervertebral disc degeneration by promoting NPC proliferation and ECM synthesis by transferring the MATN3 protein.

Validating a LEGO-Like EEG Headset for a Simultaneous Recording of Wet- and Dry-Electrode Systems During Treadmill Walking.

Recent mobile and wearable electroencephalogram (EEG)-sensing technologies have been demonstrated to be effective for measuring rapid changes of spatio-spectral EEG correlates of brain and cognitive functions of interest with more ecologically natural settings. However, commercial EEG products are available commonly with a fixed headset in terms of the number of electrodes and their locations to the scalp practically constrains their generalizability for different demands of EEG and brain-computer interface (BCI) study. While most progress focused on innovation of sensing hardware and conductive electrodes, less effort has been done to renovate mechanical structures of an EEG headset. Recently, an electrode-holder assembly infrastructure was designed to be capable of unlimitedly (re)assembling a desired n-channel electrode headset through a set of primary elements (i.e., LEGO-like headset). The present work empirically demonstrated one of its advantage regarding coordinating the homogeneous or heterogeneous sensors covering the target regions of the brain. Towards this objective, an 8-channel LEGO headset was assembled to conduct a simultaneous event-related potential (ERP) recording of the wet- and dry-electrode EEG systems and testify their signal quality during standing still versus treadmill walking. The results showed that both systems returned a comparable P300 signal-to-noise ratio (SNR) for standing, yet the dry system was more susceptible to the movement artifacts during slow walking. The LEGO headset infrastructure facilitates a desired benchmark study, e.g., comparing the signal quality of different electrodes on non-stationary subjects conducted in this work, or a specific EEG and BCI application.

Effect of BMP-2 Adherent to Resorbable Sutures on Cartilage Repair: A Rat Model of Xyphoid Process.

Meniscal tears are often seen in orthopedic practice. The current strategy for meniscal repair has only had limited success with a relatively high incidence of re-operative rate. This study evaluates the therapeutic effects of Bone morphogenetic protein-2 (BMP-2) soaked sutures for cartilage repair, using a rat model of xyphoid healing. Vicryl-resorbable sutures were presoaked in BMP-2 solutions prior to animal experimentation. Rat xyphoid process (an avascular hyaline cartilage structure) was surgically ruptured followed by repair procedures with regular suture or with sutures that were pre-soaked in BMP-2 solutions. In vitro assessment indicated that presoaking the Vicryl-resorbable sutures with 10 µg/mL BMP-2 resulted in a sustained amount of the growth factor release up to 7 days. Histological analysis suggested that application of this BMP-2 soaked suture on the rat xyphoid process model significantly improved the avascular cartilage healing compared to non-soaked control sutures. In conclusion, data here confirm that the rat xyphoid process repair is a reproducible and inexpensive animal model for meniscus and other cartilage repair. More importantly, coating of BMP-2 on sutures appears a potential avenue to improve cartilage repair and regeneration. Further study is warranted to explore the molecular mechanisms of this strategy.

Medial Dislocation of the Long Head of the Biceps without Concomitant Subscapularis Tear: A Case Report.

INTRODUCTION: Medial dislocation of the long head of the biceps tendon (LHBT) is classically known as a pathognomonic finding for a subscapularis or at least a rotator cuff (RC) injury. However, this case report outlines a young active individual with symptomatic medial dislocation of the long head of the biceps with associated posterior instability, without a corresponding RC injury. CASE REPORT: An 18-year-old male complained of the left shoulder pain and crepitus after a shoulder injury while playing hockey a year prior. Magnetic resonance imaging demonstrated medial dislocation of the LHBT without subscapularis or supraspinatus tendon injury. The patient complained of instability in the shoulder and exam findings supported posterior instability of the glenohumeral joint. Arthroscopic debridement of the glenohumeral joint with arthroscopic posterior capsulorrhaphy and open biceps tenodesis was performed. The patient regained full and painless range of motion at 2-year follow-up. CONCLUSION: Medial dislocation of the LHBT can occur without injury to the subscapularis tendon. Furthermore, a capsulorrhaphy with open biceps tenodesis and closure of the rotator interval may provide a successful outcome for this rare injury pattern.

Urine Screening for Opioid and Illicit Drugs in the Total Joint Arthroplasty Population.

INTRODUCTION: Recent studies have shown an increase in post-operative orthopaedic complications associated with pre-operative opioid use. It is, therefore, important to know if patients use opioids before scheduled surgery. The purpose of this study was to determine if urine drug screening (UDS) is an effective screening tool for detecting opioid and illicit drug use prior to joint arthroplasty (JA) procedures. METHODS: This retrospective chart review was performed with IRB approval on 166 out of 172 consecutive patients in a community-based practice. All the patients had a pre-operative UDS prior to primary or revision JA by a fellowship trained orthopaedic surgeon between March 2016 and April 2017. Patient demographics documented opioid and illicit drug use, co-morbid diagnosis, and UDS results were collected from clinical charts. Statistical analysis was conducted using Pearson Chi-square, Fisher's exact, McNemar test, and t-tests with IBM SPSS Statistics, ver. 23. Significant differences were p < 0.05. RESULTS: Sixty-four of 166 patients (38.6%) tested positive for opioids. Among them, 55.0% (35/64) had no history of prescription opioid use. Significant differences were observed when comparing the test results of the UDS with the patient reported history of prescribed opioids (p = 0.001). CONCLUSION: With a significant number of patients testing positive for opioids without evidence of a previous prescription, UDS may be beneficial for initial risk assessment for patients undergoing JA procedures.

Exosomes Derived from Human Urine-Derived Stem Cells Inhibit Intervertebral Disc Degeneration by Ameliorating Endoplasmic Reticulum Stress.

OBJECTIVE: This study is aimed at determining the effects of human urine-derived stem cell-derived exosomes (USCs-exos) on pressure-induced nucleus pulposus cell (NPC) apoptosis and intervertebral disc degeneration (IDD) and on the ERK and AKT signaling pathways. METHODS: The NPCs were obtained from patients with herniated lumbar discs. Western blot analysis (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine endoplasmic reticulum (ER) stress levels of NPCs under stress. Human USCs were identified using an inverted microscope, three-line differentiation experiments, and flow cytometry. A transmission microscope, nanoparticle size analysis, and WB procedures were used to identify the extracted exosomes and observe NPC uptake. A control group, a 48 h group, and a USCs-exos group were established. The control group was untreated, and the 48 h group was pressure-trained for 48 h, while the USCs-exos group was pressure-trained for 48 h and treated with USCs-exos. WB, qRT-PCR, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis were used to determine the ER stress levels in stress conditions and after exosomal treatment. The AKT and ERK pathways were partially detected. Magnetic Resonance Imaging (MRI) and computed tomography (CT) were used to evaluate cell degeneration while exosomal effects on the intervertebral disc (IVD) tissue were determined by hematoxylin and eosin (HE) staining, Safranin O-fast green staining, immunohistochemical staining (IHC), nuclear magnetic resonance (NMR), spectrometric detection, and total correlation spectroscopy (TOCSY). IVD metabolites were also identified and quantified. RESULTS: After pressure culture, ER stress markers (GRP78 and C/EBP homologous protein (CHOP)) in the NPCs were significantly elevated with time (p < 0.05). Human USCs are short and spindle-shaped. They can successfully undergo osteogenic, adipogenic, and chondrogenic differentiation. In this study, these stem cells were found to be positive for CD29, CD44, and CD73. The exosomes were centrally located with a diameter of 50-100 nm. CD63 and Tsg101 were highly expressed while the expression of Calnexin was suppressed. The exosomes can be ingested by NPCs. USCs-exos significantly improved ER stress responses and inhibited excessive activation of the unfolded protein response (UPR) as well as cell apoptosis and disc degeneration through the AKT and ERK signaling pathways (p < 0.05). CONCLUSION: Through the AKT and ERK signaling pathways, USCs-exos significantly inhibit ER stress-induced cell apoptosis and IDD under pressure conditions. It is, therefore, a viable therapeutic strategy.