Biocompatibility of Poly-ε-caprolactone-hydroxyapatite composite on mouse bone marrow-derived osteoblasts and endothelial cells

Open Access. Click on the DOI link to access this article at the publisher's website, or download /view it on SOAR.Background. Tissue-engineered bone may be developed by seeding the cells capable of both osteogenesis and vascularization on biocompatible composite scaffolds. The current study investigated the performance of mice bone marrow-derived osteogenic cells and endothelial cells as seeded on hydroxyapatite (HA) and poly-ε-caprolactone (PCL) composite scaffolds. Methods Mononuclear cells were induced to osteoblasts and endothelial cells respectively, which were defined by the expression of osteocalcin, alkaline phosphatase (ALP), and deposits of calcium-containing crystal for osteoblasts, or by the expression of vascular endothelial growth factor receptor-2 (VEGFR-2) and von Willebrand factor (vWF), and the formation of a capillary network in Matrigel™ for endothelial cells. Both types of cell were seeded respectively on PCL-HA scaffolds at HA to PCL weight ratio of 1:1, 1:4, or 0:1 and were evaluated using scanning electron microscopy, ALP activity (of osteoblasts) and nitric oxide production (of endothelial cells) plus the assessment of cell viability. Results The results indicated that HA led to a positive stimulation of osteoblasts viability and ALP activity, while HA showed less influence on endothelial cells viability. An elevated nitric oxide production of endothelial cells was observed in HA-containing group. Conclusion Supplement of HA into PCL improved biocompatible for bone marrow-derived osteoblasts and endothelial cells. The PCL-HA composite integrating with two types of cells may provide a useful system for tissue-engineered bone grafts with vascularization.Peer reviewe

Urine Screening for Opiod 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

Therapeutic potentials of naringin on polymethylmethacrylate induced osteoclastogenesis and osteolysis, in vitro and in vivo assessments

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Wear debris associated periprosthetic osteolysis represents a major pathological process associated with the aseptic loosening of joint prostheses. Naringin is a major flavonoid identified in grapefruit. Studies have shown that naringin possesses many pharmacological properties including effects on bone metabolism. The current study evaluated the influence of naringin on wear debris induced osteoclastic bone resorption both in vitro and in vivo. The osteoclast precursor cell line RAW 264.7 was cultured and stimulated with polymethylmethacrylate (PMMA) particles followed by treatment with naringin at several doses. Tartrate resistant acid phosphatase (TRAP), calcium release, and gene expression profiles of TRAP, cathepsin K, and receptor activator of nuclear factor-kappa B were sequentially evaluated. PMMA challenged murine air pouch and the load bearing tibia titanium pin-implantation mouse models were used to evaluate the effects of naringin in controlling PMMA induced bone resorption. Histological analyses and biomechanical pullout tests were performed following the animal experimentation. The in vitro data clearly demonstrated the inhibitory effects of naringin in PMMA induced osteoclastogenesis. The naringin dose of 10 µg/mL exhibited the most significant influence on the suppression of TRAP activities. Naringin treatment also markedly decreased calcium release in the stimulated cell culture medium. The short-term air pouch mouse study revealed that local injection of naringin ameliorated the PMMA induced inflammatory tissue response and subsequent bone resorption. The long-term tibia pin-implantation mouse model study suggested that daily oral gavage of naringin at 300 mg/kg dosage for 30 days significantly alleviated the periprosthetic bone resorption. A significant increase of periprosthetic bone volume and regaining of the pin stability were found in naringin treated mice. Overall, this study suggests that naringin may serve as a potential therapeutic agent to treat wear debris associated osteolysis

High VEGF with Rapid Growth and Early Metastasis in a Mouse Osteosarcoma Model

A murine model of osteosarcoma was developed to investigate the association between the expression of VEGF and the progression of osteosarcoma. Two human osteosarcoma cell lines with distinct VEGF expressions were introduced into proximal tibiae of immuno-deficient SCID mice, either by direct injection through the cortical bone or surgical exposing and drilling on the tibial metaphysis to seed tumor cells. Bone tumors were obvious on microCT within 4 weeks following osteosarcoma cell inoculation through surgical delivery. In contrast, direct injection without drilling often resulted in periosteal tumors. Although neoplasms were developed regardless of VEGF levels, orthotopic tumors derived from high VEGF-expressing cells were detected 2 weeks earlier on CT images than the ones from VEGF negative cells. At sacrifice, high VEGF tumors were distinctively larger in size and more frequently invaded the adjacent bone tissue. Multiple metastatic lesions were found in all the lung tissues at 8 weeks from high VEGF group, whereas only 1 of 7 VEGF negative tumors exhibited pulmonary metastasis. Overall, this model developed with the surgical tumor cell delivery results in histological and radiographic features more consistent with primary osteosarcoma. Interestingly, VEGF expression correlates with the early establishment, rapid tumor growth, and the development of pulmonary metastasis

Local Gene Transfer of OPG Prevents Joint Damage and Disease Progression in Collagen-Induced Arthritis

This study examined the influence of osteoprotegerin (OPG) gene transfer on a murine collagen-induced arthritis model. A single periarticular injection of AAV-OPG or AAV-LacZ on the arthritic paw successfully incorporated the exogenous gene to the local tissue and resulted in marked transgene expression in the joint homogenate for at least three weeks. Clinical disease scores were significantly improved in OPG treated mice starting at 28-day post-treatment (P<0.05). Histological assessment demonstrated that OPG gene transfer dramatically protected mice from erosive joint changes compared with LacZ controls (P<0.05), although treatment appeared less effective on the local inflammatory progress. MicroCT data suggested significant protection against subchondral bone mineral density changes in OPG treated CIA mice. Interestingly, mRNA expressions of IFN-g and MMP3 were noticeably diminished following OPG gene transfer. Overall, gene transfer of OPG effectively inhibited the arthritis-associated periarticular bone erosion and preserved the architecture of arthritic joints, and the study provides evidence that the cartilage protection of the OPG gene therapy may be associated with the down-regulation of MMP3 expression

Clinical characteristics and risk factors associated with ICU-acquired infections in sepsis: A retrospective cohort study

Intensive care unit (ICU)-acquired infection is a common cause of poor prognosis of sepsis in the ICU. However, sepsis-associated ICU-acquired infections have not been fully characterized. The study aims to assess the risk factors and develop a model that predicts the risk of ICU-acquired infections in patients with sepsis.MethodsWe retrieved data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients were randomly divided into training and validation cohorts at a 7:3 ratio. A multivariable logistic regression model was used to identify independent risk factors that could predict ICU-acquired infection. We also assessed its discrimination and calibration abilities and compared them with classical score systems.ResultsOf 16,808 included septic patients, 2,871 (17.1%) developed ICU-acquired infection. These patients with ICU-acquired infection had a 17.7% ICU mortality and 31.8% in-hospital mortality and showed a continued rise in mortality from 28 to 100 days after ICU admission. The classical Systemic Inflammatory Response Syndrome Score (SIRS), Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Charlson Comorbidity Index (CCI), and Acute Physiology Score III (APS III) scores were associated with ICU-acquired infection, and cerebrovascular insufficiency, Gram-negative bacteria, surgical ICU, tracheostomy, central venous catheter, urinary catheter, mechanical ventilation, red blood cell (RBC) transfusion, LODS score and anticoagulant therapy were independent predictors of developing ICU-acquired infection in septic patients. The nomogram on the basis of these independent predictors showed good calibration and discrimination in both the derivation (AUROC = 0.737; 95% CI, 0.725–0.749) and validation (AUROC = 0.751; 95% CI, 0.734–0.769) populations and was superior to that of SIRS, SOFA, OASIS, SAPS II, LODS, CCI, and APS III models.ConclusionsICU-acquired infections increase the likelihood of septic mortality. The individualized prognostic model on the basis of the nomogram could accurately predict ICU-acquired infection and optimize management or tailored therapy

Planar p-n Junction Based on a TMDs/Boron Nitride Heterostructure

Transition metal dichalcogenides (TMDs) are attracting growing interest for their prospective application in electronic and optical devices. As a leading material in researches of two-dimensional (2D) electronics, although band structure is layer-dependent, the TMDs show ambipolar properties. While optically excited light emission has been widely investigated, study on electrically generated emission is still limited. Taking the advantage of its ambipolarity and presence of direct band-gap in monolayer, we developed an electrically driven light emitting device based on stacked 2D flakes to obtain sharp planar p-n junction in monolayer. Specifically, we have fabricated atomic-layer TMDs/boron nitride (BN) artificial heterostructures using stacked h-BN thin flake as a mask to partially cover the TMDs transistor channel allowing high-density hole accumulation (p-region) via localized exposure to gate-controlled accumulation of anions. Transport through the junction shows typical diode-like rectification current with accompanying strong and sharp light emission from the crystal edge of BN mask for the monolayer case.</p

Smart membranes for oil/water emulsions separation: a review

Oily wastewater poses a significant impact on both environments and human societies. Especially, the treatment of oil/water emulsions for separating oil from water is challenging due to the high stability of oil/water emulsions. Smart membranes, known as stimuli-responsive membranes, are one of the emerging technologies that have been paid wide attention for separating oil/water emulsions in recent years. Smart membranes possess the unique features of switchable wettability between hydrophilicity and hydrophobicity after being triggered by external stimuli and have desired anti-fouling properties. This review summarizes the development of smart membranes for oil/water emulsions separation during the past five years (2018 – present). It was found that solvent stimuli-responsive membranes are the most popular type of smart membranes for oil/water emulsions separation. For multi-stimuli-responsive membranes that can respond to more than one stimulus, future research should focus on developing appropriate fabrication strategies to increase the separation and anti-fouling performances of the membranes. Additionally, surface coating, surface grafting, and copolymer blending are the most popular methods for smart membranes fabrication. However, these methods might not be universally applicable to the different types of stimuli-responsive membranes