Bacteriosynthetic Degradable Tranexamic Acid-Functionalized Short Fibers for Inhibiting Invisible Hemorrhage.

Current research on hemostatic materials have focused on the inhibition of visible hemorrhage, however, invisible hemorrhage is the unavoidable internal bleeding that occurs after trauma or surgery, leading directly to a dramatic drop in hemoglobin and then to anemia and even death. In this study, bacterial nanocellulose (BNC) was synthesized and oxidized from the primary alcohols to carboxyl groups, and then grafted with tranexamic acid through amide bonds to construct degradable nanoscale short fibers (OBNC-TXA), which rapidly activated the coagulation response. The hemostatic material is made up of nanoscale short fibers that can be constructed into different forms such as emulsions, gels, powders, and sponges to meet different clinical applications. In the hemostatic experiments in vitro, the composites had significantly superior pro-coagulant properties due to the rapid aggregation of blood cells. In the coagulation experiments with rat tail amputation and liver trauma hemorrhage models, the group treated with OBNC-TXA1 sponge showed low hemorrhage and inhibited invisible hemorrhage in rectus abdominis muscle defect hemorrhage models, with a rapid recovery of hemoglobin values from 128±5.5 to 165±2.6 g L-1 within 4 days. In conclusion, the degradable short fibers constructed from bacterial nano-cellulose achieved inhibition of invisible hemorrhage in vivo.

Size and Ultrasound Features Affecting Results of Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules.

OBJECTIVES: Our goal was to assess the diagnostic efficacy of ultrasound (US)-guided fine-needle aspiration (FNA) of thyroid nodules according to size and US features. METHODS: A retrospective correlation was made with 1745 whole thyroidectomy and hemithyroidectomy specimens with preoperative US-guided FNA results. All cases were divided into 5 groups according to nodule size (≤5, 5.1-10, 10.1-15, 15.1-20, and >20 mm). For target nodules, static images and cine clips of conventional US and color Doppler were obtained. Ultrasound images were reviewed and evaluated by two radiologists with at least 5 years US working experience without knowing the results of pathology, and then agreement was achieved. RESULTS: The Bethesda category I rate was higher in nodules larger than 15 mm (P < .05). The diagnostic accuracy was best in nodules of 5 to 10 mm in diameter. The sensitivity, accuracy, PPV, and LR for negative US-guided FNA results were better in nodules with a size range of 5 to 15 mm. The specificity, negative predictive value (NPV), and LR for positive results and the Youden index rose with increasing nodule size. Seventeen false-positive and 60 false-negative results were found in this study. The false-negative rate rose with increasing nodule size. However, the false-positive rate was highest in the group containing the smallest nodules. Nodules with circumscribed margins and those that were nonsolid and nonhypoechoic and had no microcalcifications correlated with Bethesda I FNA results. Nodules with circumscribed margins and those that were nonsolid, heterogeneous, and nonhypoechoic and had increased vascularity correlated with false-negative FNA results. Borders correlated with Bethesda I false-negative and false-positive FNA results. CONCLUSIONS: Tiny nodules (≤5 mm) with obscure borders tended to yield false-positive FNA results. Large nodules (>20 mm) with several US features tended to yield false-negative FNA results.

The value of EUS in combination with cytological, flow cytometry, and gene rearrangement in the diagnosis of gastrointestinal lymphoma.

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) have a great value in clinical practice of gastrointestinal lymphoma (GIL). Auxiliary methods such as flow cytometry (FCM) and gene rearrangement provide additional information for the diagnosis. Current study aims to explore the diagnostic value of EUS-FNA combined with FCM and gene rearrangement for GIL in our single institution. Suspected GIL cases, which were referred to EUS, FNA, FCM, or gene rearrangement examination, were retrospectively reviewed from January 2011 to May 2014. Definitive final diagnosis was included based on the pathological and immunostaining evidence. The gene scan analysis was applied for fragment detection in gene rearrangement. The sensitivity, specificity, and accuracy were considered and calculated. Fifty-three EUS cases were identified, including 38 GIL, 10 inflammations, 4 linitis plastica, and one multiple myeloma. EUS-FNA was successfully conducted in 39 out of 53 cases. After combined with FCM, the sensitivity, specificity, and accuracy were increased from 60.7% to 76.9%, 90.9% to 100%, and from 69.2% to 81.8% respectively. Among 33 cases for FCM, 11 of them gained positive B or T non-Hodgkin lymphoma diagnosis, and 28 out of 53 specimens were delivered for gene rearrangement. The sensitivity, specificity, and accuracy of gene rearrangement were 68.2%, 100%, and 75% respectively. EUS-FNA is a possible technique for the diagnosis of GIL, With additional FCM examination may further improve the diagnostic efficiency and facilitate subclassification. Moreover, gene rearrangement assay by gene scan is also a considerable method in the specimens from GIL. Copyright © 2016 John Wiley & Sons, Ltd.

Axillary Staging of Early-Stage Invasive Breast Cancer by Ultrasound-Guided Fine-Needle Aspiration Cytology: Which Ultrasound Criteria for Classifying Abnormal Lymph Nodes Should Be Adopted in the Post-ACOSOG Z0011 Trial Era?

OBJECTIVES: Ultrasound (US)-guided fine-needle aspiration cytology (FNAC) is able to identify patients with extensive node involvement before surgery. In this study, we aimed to establish the optimal US criterion to identify abnormal lymph nodes on US-guided FNAC for detection of patients with 3 or more metastatic axillary nodes. METHODS: A total of 445 axillae from 443 patients with histologically confirmed invasive breast cancer (cT1-2 cN0) were examined with US at Ruijin Hospital from August 2013 to August 2014. Ultrasound-guided FNAC was performed on suspicious nodes when the cortex was eccentrically or concentrically thickened to greater than 2 mm; 269 axillae (60.4%) met the criterion and underwent US-guided FNAC. We retrospectively analyzed the US characteristics of axillary lymph nodes, the US-guided FNAC results, and the extent of axillary nodal involvement. For diagnostic performance, the sensitivity, specificity, and receiver operating characteristic curves were obtained. RESULTS: Eighty-six patients (19.4%) were confirmed to have 3 or more positive lymph nodes by pathologic analysis. There was a significant association between the morphologic change in the most suspicious node and the extent of axillary nodal involvement (P < .001). When we applied the cutoff point (cortical thickness >3.5 mm) at which the maximal sum of sensitivity and specificity for diagnosis of 3 or more axillary lymph node metastases was achieved, we found that the sensitivity and specificity were 75.6% and 82.7%, respectively. When combining this criterion with US-guided FNAC of the most suspicious nodes, the sensitivity and specificity were 64.2% and 94.5%, and 36.1% of cases could be spared an unnecessary 1-step axillary lymph node dissection. CONCLUSIONS: Cortical thickness of greater than 3.5 mm in the most suspicious nodes is appropriately predictive of patients with 3 or more tumor-involved axillary nodes. When this criterion for US-guided FNAC was adopted, a group of patients with 1 or 2 metastatic nodes could be spared unnecessary 1-step axillary lymph node dissection.

Key genes associated with osteoporosis revealed by genome wide gene expression analysis.

Gene expression profiles of circulating monocytes were analyzed to identify key genes associated with osteoporosis. Raw microarray data were downloaded from gene expression omnibus under accession number GSE7158, including 8 microarray dataset for patients with high peak bone mass (PBM) and 8 for low PBM. Package linear models for microarray data of R was adopted to screen out differentially expressed genes (DEGs). Gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed with plug-ins of cytoscape. Protein-protein interaction network was constructed using FunCoup. A total of 283 DEGs were identified in low-PBM group, including 135 up- and 148 down-regulated genes. A considerable part of DEGs were localized in plasma membrane. Several ion transport-related pathways were revealed, such as mineral absorption and carbohydrate digestion and absorption. A range of DEGs were identified and some of them were related to calcium transport as well as osteoporosis. These findings are helpful in disclosing the pathogenetic mechanisms of osteoporosis.

The impact of audience dynamics on public speaking anxiety in virtual scenarios: An online survey.

BACKGROUND: Public speaking is one of the most commonly feared situations reported in both community and university samples. Despite extensive theoretical models and empirical studies aimed at delineating the underlying factors of Public Speaking Anxiety (PSA), the specific variables contributing to its onset remain incompletely characterised. METHODS: The research involved 297 participants from an AmazonTurk survey, engaging with virtual public speaking scenarios differentiated by audience size, engagement levels, and room spatial dimensions. Participants' anticipated anxiety levels were quantitatively assessed across these scenarios, enabling a comprehensive exploration of the interaction between situational variables and PSA, thereby providing a framework to explore the influence of audience size, engagement, and spatial dimensions on PSA. RESULTS: The mixed-effect model revealed a significant interaction among audience size, audience engagement, and room spatial dimensions. Further analyses using principal axis factoring and multiple regression identified three main factors: F1 (Engagement in a Large Audience), F2 (Confinement or Evaluation Anxiety), and F3 (Audience Disengagement). These factors significantly predict PSA scores. CONCLUSIONS: This study reveals that PSA is influenced by a complex interplay of audience size, room dimensions, and audience engagement. The finding underscores the viable way to incorporate these situational variables in both empirical investigations and therapeutic interventions. Specifically, it introduces a novel framework for standardising audience size relative to room capacity.

Proximal humeral bone density assessment and prediction analysis using machine learning techniques: An innovative approach in medical research.

Background: Patients with fractures of the proximal humerus often local complications and failures attributed to osteoporosis. Currently, there is a lack of straight forward screening methods for assessing the extent of local osteoporosis in the proximal humerus. This study utilizes machine learning techniques to establish a diagnostic approach for evaluating local osteoporosis by analyzing the patient's demographic data, bone density, and X-ray ratio of the proximal humerus. Methods: A cohort comprising a total of 102 hospitalized patients admitted during the period spanning from 2021 to 2023 underwent random selection procedures. Resulting in exclusion of 5 patients while enrolling 97 patients for analysis encompassing patient demographics, shoulder joint anteroposterior radiographs, and bone density information. Using the modified Tingart index methodology involving multiple measurements denoted as M1 through M4 obtained from humeral shafts. Within this cohort comprised 76 females (78.4 %) and 21 males (21.6 %), with an average age of 73.0 years (range: 43-98 years). There were 25 cases with normal bone density, 35 with osteopenia, and 37 with osteoporosis. Machine learning techniques were used to randomly divide the 97 cases into training (n = 59) and validation (n = 38) sets with a ratio of 6:4 using stratified random sampling. A decision tree model was built in the training set, and significant diagnostic indicators were selected, with the performance of the decision tree evaluated using the validation set. Multinomial logistic regression methods were used to verify the strength of the relationship between the selected indicators and osteoporosis. Results: The decision tree identified significant diagnostic indicators as the humeral shaft medullary cavity ratio M2/M4, age, and gender. M2/M4 ≥ 1.13 can be used as an important screening criterion; M2/M4 < 1.13 was predicted as local osteoporosis; M2/M4 ≥ 1.13 and age ≥83 years were also predicted as osteoporosis. M2/M4 ≥ 1.13 and age <64 years or males aged between 64 and 83 years were predicted as the normal population; M2/M4 ≥ 1.13 and females aged between 64 and 83 years were predicted as having osteopenia. The decision tree's accuracy in the training set was 0.7627 (95 % CI (0.6341, 0.8638)), and its accuracy in the test set was 0.7895 (95 % CI (0.6268, 0.9045)). Multinomial logistic regression results showed that humeral shaft medullary cavity ratios M2/M4, age, and gender in X-ray images were significantly associated with the occurrence of osteoporosis. Conclusion: Utilizing X-ray data of the proximal humerus in conjunction with demographic information such as gender and age enable the prediction of localized osteoporosis, facilitating physicians' rapid comprehension of osteoporosis in patients and optimization of clinical treatment plans. Level of evidence: Level IV retrospective case study.

Clinical and radiological outcomes of acute Rookwood type IIIB acromioclavicular joint dislocation: Mini-open tightrope technique versus hook plate.

OBJECTIVE: Treatment of acute Rookwood type III AC joint dislocation is still controversially discussed. ISAKOS suggested to subdivide type III AC joint injuries into type IIIA (stable) and type IIIB (unstable). The aim of this study was to compare clinical and radiographic outcomes between hook plate fixation and mini-open tightrope for the treatment of acute Rookwood type IIIB acromioclavicular joint dislocation. METHODS: We conducted a retrospective clinical study of 112 patients with acute Rookwood type IIIB acromioclavicular joint dislocation who were treated surgically using either mini-open TightRope or hook plate from 2013 to 2019. All patients were followed up for 12 months. Clinical outcomes were evaluated using Visual Analogue Scale (VAS) and the Constant-Murley Score (CMS). Radiological results were assessed with the coracoclavicular distance (CCD), the change in clavicular elevation (ΔCE) and horizontal translation. RESULTS: The length of incision was significantly shorter in the mini-open TightRope group than that in hook plate group (6.62±0.60 vs. 2.58±0.43 p <0.001). Duration of surgery was significantly shorter in the mini-open TightRope group than that in hook plate group (30.12±6.65 vs. 53.33±12.03; p < 0.001). Total blood loss volume was significantly less in the mini-open TightRope group than in the hook plate group. (23.85±7.88 vs. 70.67±24.62, p < 0.001). VAS and CMS in mini-open TightRope group were better than that in hook plate group at 2 weeks after surgery (VAS: 2.19±0.92 vs. 3.30±1.51, p = 0.002 and CMS 69.80±5.61 vs. 57.53±9.24, p<0.001) and 3 month after surgery (VAS: 1.19±0.48 vs. 3.07±1.36, p<0.001 and CMS 89.30±4.47 vs. 83.20±12.11, p = 0.205). There was no statistically significant difference between two groups at 12 months follow-up including VAS, CMS, the CC distance,ΔCE and the degree of dynamic horizontal translation. There were 2 complications in the hook plate group including 1cut out and 1 superficial wound infection. CONCLUSION: The mini-open tightrope has better function and relieves pain in the early postoperative period compared to hook plate, and at the last follow up two groups have similar clinical and radiological outcomes. Mini-open TightRope fixation is a good option for the treatment of acute Rockwood types ⅢB AC joint dislocation.

Revising the modified Neer classification for distal clavicle fractures: Description and reliability.

BACKGROUND: The modified Neer classification is the most widely used classification system for distal clavicle fractures. However, it provides limited information for treatment decisions. The objective of this study was to revise the modified Neer classification to make it more suitable for treatment decision-making. HYPOTHESIS: The revised version of the modified Neer classification has good intra- and interobserver agreements and provides an instructive treating algorithm. STUDY DESIGN: Cohort study METHODS: Six observers, including three experienced shoulder specialists and three junior orthopaedic residents, independently reviewed plain radiographs of 52 patients with distal clavicle fractures. They were asked to classify the fracture types according to the modified Neer classification and our revised new classification separately to determine treatment approaches for each patient. Images were mirrored and randomized to verify the intraobserver agreement. Reliabilities were measured using the Fleiss kappa values. RESULTS: Both the modified Neer classification and our revised version had near perfect intraobserver agreement (κ values: 0.87-1.00), whereas our revised Neer classification had a better interobserver agreement (κ values: 0.78 vs. 0.70, z = 4.70, p < 0.01) and stronger relevance to treatment decisions (coefficient of contingency: 0.70 vs. 0.44). CONCLUSION: Our study demonstrated a near-perfect intraobserver and substantial interobserver agreement of the revised new classification, indicating that our revised new classification was better than the modified Neer classification. Meanwhile, our revised classification brought few disputes in treatment selection. CLINICAL RELEVANCE: The modified Neer classification was revised to make it more accurate and suitable for guiding treatment. TYPE OF STUDY: Study of diagnostic test LEVEL OF STUDY: Level II.

Circadian Clock Regulation via Biomaterials for Nucleus Pulposus.

Circadian clock disorder during tissue degeneration has been considered the potential pathogenesis for various chronic diseases, such as intervertebral disc degeneration (IVDD). In this study, circadian clock-regulating biomaterials (ClockMPs) that can effectively activate the intrinsic circadian clock of nucleus pulposus cells (NPCs) in IVDD and improve the physiological function of NPCs for disc regeneration are fabricated via air-microfluidic technique and the chemical cross-linking between polyvinyl alcohol and modified-phenylboronic acid. In vitro experiments verified that ClockMPs can scavenge reactive oxygen species to maintain a stable microenvironment for the circadian clock by promoting the binding of BMAL1 and CLOCK proteins. ClockMPs can regulate the expression of core circadian clock genes by activating the PI3K-AKT pathway in NPCs to remodel the intrinsic circadian clock and promote extracellular matrix synthesis. Furthermore, in vivo experiments of IVDD treated with ClockMPs proved that ClockMPs can promote disc regeneration by regulating the circadian clock of NPCs. In conclusion, ClockMPs provided a novel and promising strategy for circadian clock regulation during tissue regeneration.

In Situ Sustained Macrophage-Targeted Nanomicelle-Hydrogel Microspheres for Inhibiting Osteoarthritis.

There are still challenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation, due to the rapid clearance of nanocarriers and burst drug release in vivo. Herein, a nanomicelle-hydrogel microsphere, characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis, is employed for in situ sustained macrophage targeting and regulation, and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers. The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle, thus keeping it in joints, while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages, and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages. The experiments show that the nanomicelle-hydrogel microsphere can in situ sustainably target and regulate M1 macrophages for more than 14 days in joints, and attenuate local "cytokine storm" by continuous M1 macrophage apoptosis promotion and polarization inhibition. This micro/nano-hydrogel system shows excellent ability to sustainably target and regulate macrophage, realizes the improvement of drug utilization and efficacy inside the macrophage, and thereby can be a potential platform for treating macrophage-related diseases.

Three-dimensional morphology of microdamage in peri-screw bone: a scanning electron microscopy of methylmethacrylate cast replica.

Screw implantation inevitably causes microdamage in surrounding bone. However, little is known about the detailed characteristics of microdamage in peri-screw bone. In this study, we developed a method to construct microdamage cast with methylmethacrylate (MMA) and observed the cast using scanning electron microscopy (SEM). In basic fuchsin stained bone sections observed by bright-field and fluorescence microscopy, diffuse damage, cross-hatched damage, and linear cracks were all presented in peri-screw bone. Using MMA casting/SEM method, we found numerous densely packed microcracks in the areas with diffuse damage. The osteocyte canaliculi and the microcracks consisting of diffuse damage had a similar diameter (or width), usually <0.5 µm, but their morphology was largely different. In the area with cross-hatched damage, the orientation of microcracks was similar to that in diffuse damage, but the number was significantly decreased. Many microcracks were thicker than 1 µm and associated with a rough surface. Large linear cracks (∼10 µm in diameter) occurred in different areas. Plenty of microcracks were present on the surface of some linear cracks. In conclusion, the MMA casting/SEM method can demonstrate the three-dimensional morphology of different types of microdamage, particularly the microcracks in diffuse damage, which are unable to be shown by light microscopy.

Gradient bimetallic ion-based hydrogels for tissue microstructure reconstruction of tendon-to-bone insertion.

Although gradients play an essential role in guiding the function of tissues, achieving synchronous regeneration of gradient tissue injuries remains a challenge. Here, a gradient bimetallic (Cu and Zn) ion-based hydrogel was first constructed via the one-step coordinative crosslinking of sulfhydryl groups with copper and zinc ions for the microstructure reconstruction of the tendon-to-bone insertion. In this bimetallic hydrogel system, zinc and copper ions could not only act as crosslinkers but also provide strong antibacterial effects and induce regenerative capacity in vitro. The capability of hydrogels in simultaneously promoting tenogenesis and osteogenesis was further verified in a rat rotator cuff tear model. It was found that the Cu/Zn gradient layer could induce considerable collagen and fibrocartilage arrangement and ingrowth at the tendon-to-bone interface. Overall, the gradient bimetallic ion-based hydrogel ensures accessibility and provides opportunities to regenerate inhomogeneous tissue with physiological complexity or interface tissue.

The patterns and management of fracture patients under COVID-19 outbreak in China.

BACKGROUND: Currently, the perioperative care of fracture patients is compromised due to the outbreak of COVID-19 in China and the world. This study aims to assess the clinical features of fracture patients at our hospital during the COVID-19 outbreak and formulate the medical steps to ensure the effective treatment of fracture patients with minimal risk of infection to healthcare workers. METHODS: One hundred twelve patients with different fractures that were admitted to the orthopedics department of our hospital from January 24 to March 9 in 2020 were reviewed. Data including age, gender, injury location, admission time, operation time, discharge time were compared with fracture patients from the same period in 2019. RESULTS: Compared to the same period in 2019, there is a 42% decrease in the number of fracture patients in 2020. Specifically, the incidences of forearm, thigh, hand, and foot fractures have increased during the COVID-19 outbreak, while other parts are less affected. The time from injury to hospitalization, the surgery wait time and time of discharge after surgery for patients with hip fractures were 2.9±7.1, 2.0±1.7 and 7.7±4.0 days respectively in 2019, which changed to 2.0±5.0, 4.5±4.0 and 10.6±4.2 days in 2020. Following the orthopedic treatment regimen followed at our hospital, all patients had non-life-threatening limb fractures. Six patients were operated in a negative pressure room, and emergency screening was completed for six patients. No patients were positive for COVID-19, and all were discharged safely without infection or other serious complications. CONCLUSIONS: Hip fractures are highly prevalent during this epidemic. However, mandatory screening delays surgery by more than 48 hours. The orthopedic department should prioritize screening of emergency patients to minimize the risk of infection among other patients and medical personnel.

Stable ZnO-doped hydroxyapatite nanocoating for anti-infection and osteogenic on titanium.

Titanium and titanium alloys have been widely used in orthopedics and related fields. However, their clinical applications are limited due to the lack of anti-infection, osteoinductivity and angiogenic ability. In the present study, we utilized pulse electrochemical deposition method to prepare polypyrrole (PPy) by the in-situ oxidative polymerization of pyrrole (Py), and through the coordination and doping of ions, the function of PPy as a dual regulator of hydroxyapatite nanoparticles (HA-NPs) and zinc oxide nanoparticles (ZnO-NPs) was achieved. Bioactivity test showed that the composite coating could induce the formation of apatite, and the apatite was in a neat arrangement preferentially grew along the (002) crystal plane, indicating good bioactivity. The release test showed that the dual regulation effect of PPy coordination and doping reduced the release rate of Ca2+ and Zn2+ from the composite coating. Antibacterial tests showed that the composite coating against Escherichia coli and Staphylococcus aureus. Besides, bone marrow-derived mesenchymal stem cells (BMSCs) exhibited good adhesion, proliferation and differentiation on the composite coating, and fluorescence staining experiments demonstrated good osteoinductivity of the composite coating. In this study, a multifunctional composite coating with anti-infection, angiogenic and osteoinductivity was successfully constructed on the titanium surface via pulse electrochemical deposition method.

Electrospun fibers: an innovative delivery method for the treatment of bone diseases.

INTRODUCTION: The treatment performances of current surgical therapeutic materials for injuries caused by high-energy trauma, such as prolonged bone defects, nerve-fiber disruptions, and repeated spasms or adhesions of vascular tendons after repair, are poor. Drug-loaded electrospun fibers have become a novel polymeric material for treating orthopedic diseases owing to their three-dimensional structures, thus providing excellent controlled drug-release responses and high affinity with local tissues. Herein, we reviewed the morphology of electrospun nanofibers, methods for loading drugs on the fibers, and modification methods to improve drug permeability and bioavailability. We highlight innovative applications of drug-loaded electrospun fibers in different treatments, including bone and cartilage defects, tendon and soft-tissue adhesion, vascular remodeling, skin grafting, and nervous-system injuries. AREAS COVERED: With the rapid development of electrospinning technologies and advancement of tissue engineering, drug-loaded electrospun fibers are becoming increasingly important in controlled drug release, wound closure, and tissue regeneration and repair. EXPERT OPINION: Drug-loaded electrospun fibers exhibit a broad range of application prospects and great potential in treating orthopedic diseases. Accordingly, a plethora of novel treatments utilizing the different morphological features of electrospun fibers, the distinctive pharmacokinetics, pharmacodynamics characteristics of different drugs, and the diverse onset characteristics of different diseases, is proposed.

Improvement of calcium phosphate scaffold osteogenesis in vitro via combination of glutamate-modified BMP-2 peptides.

Alpha-tricalcium phosphate (α-TCP) based porous scaffolds have superior osteoconduction and osteoinduction in bone tissue engineering, furthermore, these 3D porous scaffolds can be used as efficient drug delivery carriers. In the concept of tissue engineering, the "drugs" could be defined as drug molecules or biomacromolecules, even cells. These "drugs" have endowed the scaffolds which were laden improved abilities compared with the blank scaffolds. In this study, we anchored osteogenic bone morphogenetic protein-2 (BMP-2) derived peptides to α-TCP 3D porous scaffolds by linking the E7 domain to the target peptides, constructed the modified active peptides (E7BMP-2 peptides) delivery system, which finally achieved the modified peptides sustaining release and enhanced rat bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in vitro. The α-TCP 3D porous scaffolds had micropores and interconnected micropores which expanded surface area of the scaffolds. The release test testified the constructed the delivery system had realized long-term release in which the peptides dosage could be detected by the BCA protein assay kit after 10 days compared with BMP-2 proteins which absorbed on the same α-TCP 3D porous scaffolds. The constructed E7BMP-2 peptides delivery system supported rat BMSCs osteogenic differentiation in the form of improving the genes expression levels of Runx2, ALP and OCN. Based on electrostatic interactions, E7 domain fastened combination between the active BMP-2 derived peptides and the α-TCP 3D porous scaffolds, the sustaining E7BMP-2 peptides release promoted the BMSCs osteogenesis as BMP-2 proteins did, which endowed α-TCP 3D porous scaffolds enhanced osteoinductive abilities in vitro.

Osteogenic and antiseptic nanocoating by in situ chitosan regulated electrochemical deposition for promoting osseointegration.

Ti and titanium alloy have been extensively utilized in the areas of orthopedics and other related fields, however, limited abilities in antibiosis, ossification and vascularization restrict the application of these materials in clinical. In this research, pulse electrochemical deposition was used as a method to make chitosan regulate Ag+ and Ca2+ in situ, achieving ions' dual regulations and coprecipitation of HA nanoparticles (HA-NPs) and Ag nanoparticles (Ag-NPs) on the surface of Ti. The spherical nanoparticles with even distribution were fabricated by optimizing deposition potential and the concentration of Ag+. The physical stabilities of coatings were significantly improved by the chelation among CS, Ag+ and Ca2+ reducing the release rate of Ag+, Ca2+. The coatings also exhibited noticeable abilities in anti-bacteria. Bone marrow mesenchymal stem cells (BMSCs) displayed adhesion, proliferation and differentiation abilities on the surface of coatings, at the same time the composite coatings revealed promising capability in inducing BMSCs differentiation to osteoblast, which is proved by the results of fluorescent dye. Similar results also can be found in investigations about vascular endothelial cells, desirable adhesion between cells and materials and proliferation are able to prove that this kind of materials has outstanding biocompatibility with VECs cells. The animal experiments indicated that the composite coatings were biocompatible with smooth muscle, myocardium and lung with slightly negative impacts on liver and kidney. According to the results of alizarin red staining, the calcified nodules were dyed red, which reveal that this material can promote bone formation. Electrochemical method was utilized in this research to successfully construct multifunctional composite coatings, such as antibiosis, osteogenesis and angiogenesis, on the surface of Ti.

Outer-inner dual reinforced micro/nano hierarchical scaffolds for promoting osteogenesis.

Biomimetic scaffolds have been extensively studied for guiding osteogenesis through structural cues. Inspired by the natural bone growth process, we have employed a hierarchical outer-inner dual reinforcing strategy, which relies on the interfacial ionic bond interaction between amine/calcium and carboxyl groups, to build a nanofiber/particle dual strengthened hierarchical silk fibroin scaffold. This scaffold can provide an applicable form of osteogenic structural cue and mimic the natural bone forming process. Owing to the active interaction between compositions located in the outer pore space and the inner pore wall, the scaffold has over 4 times improvement in the mechanical properties, followed by a significant alteration of the cell-scaffold interaction pattern, demonstrated by over 2 times elevation in the spreading area and enhanced osteogenic activity potentially involving the activities of integrin, vinculin and Yes-associated protein (YAP). The in vivo performance of the scaffold identified the inherent osteogenic effect of the structural cue, which promotes rapid and uniform regeneration. Overall, the hierarchical scaffold is promising in promoting uniform bone regeneration through its specific structural cue endowed by its micro-nano construction.

Identification and characterization of mouse Gas6 promoter.

In this study, we identify and characterize the promoter of the mouse Gas6 gene, a negative regulator of chondrogenic differentiation. We identified two highly conserved regions within the core Gas6 promoter, which are conserved among mouse, human, and rat Gas6 genes, named A-BOX and B-BOX. Basal transcriptional activity was significantly reduced after deletion of either the A-BOX or the latter half of the B-BOX. After treatment with BMP-2 for 3 days, putative A-BOX Binding Factor(s) B (ABFB) and B-BOX Binding Factor(s) (BBF) were unable to bind to their specific motifs in C3H10T1/2 cells, compared with untreated control cells. In addition, we confirmed binding of an NF-Y site within the core promoter region of mouse Gas6 gene. Taken together, these observations provide insight into the mechanism by which Gas6 is downregulated during mesenchymal stem cells differentiation into chondrocytes.