Hybrid Electrospun Polycaprolactone Mats Consisting of Nanofibers and Microbeads for Extended Release of Dexamethasone.

PURPOSE: We designed electrospun polycaprolactone mats consisting of nanofibers and microbeads for extended delivery of dexamethasone. METHODS: Thin flexible dexamethasone loaded polycaprolactone mats were prepared by electrospinning. The solvents, polymer loading, voltage and tip-to-collector distance were varied to explore the effects on microstructure of the mats. The microstructure was determined by scanning electron microscope imaging; drug transport was measured and modeled, and X-ray diffraction was used to gauge the crystallinity. Drug transport and X-ray diffraction studies were also conducted with a spin cast film for comparison. RESULTS: Thin mats, about 10 µm in thickness, were prepared by electrospinning. By controlling the voltage and tip-to-collector distance, we achieved a hybrid structure comprising of nanorods (nanofibers) and microbeads. The release profiles were fitted to the diffusion equation to obtain the diffusivities in the spheres and the rods. The diffusivity in the electrospun nanofibers was significantly lower compared to the casted films due to increased crystallinity, which was estimated from X-ray diffraction analysis. The electrospun hybrid mats sustained drug release for the desired duration of a month, in spite of the small thickness of about 10 µm. By comparison, a ten-fold thicker cast film sustains release for about the same duration suggesting about 100-fold decrease in diffusivity in the electrospun mats due to increased crystallinity. CONCLUSIONS: Electrospun polycaprolactone mats are optimal for achieving long release durations due to increased crystallinity. Designing a hybrid structure by controlling the electrospinning parameters can be a useful approach to increase the release durations.

The Comparison between Cemented and Uncemented Hemiarthroplasty in Patients with Femoral Neck Fractures: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Hemiarthroplasty is the standard treatment for patients with femoral neck fractures (FNFs). Controversy exists over the use of bone cement in hip fractures treated with hemiarthroplasty. OBJECTIVE: We performed an updated systematic review and meta-analysis to compare cemented and uncemented hemiarthroplasty in patients with femoral neck fractures. METHODS: A literature review was conducted using Cochrane Library, ScienceDirect, PubMed, Embase, Medline, Web of Science, CNKI, VIP, Wang Fang, and Sino Med databases. Studies comparing cemented with uncemented hemiarthroplasty for FNFs in elderly patients up to June 2022 were included. Data were extracted, meta-analyzed, and pooled as risk ratios (RRs) and weighted mean differences (WMDs) with a 95% confidence interval (95% CI). RESULTS: Twenty-four RCTs involving 3471 patients (1749 cement; 1722 uncemented) were analyzed. Patients with cemented intervention had better outcomes regarding hip function, pain, and complications. Significant differences were found in terms of HHS at 6 weeks (WMD 12.5; 95% CI 6.0-17.0; P < 0.001), 3 months (WMD 3.3; 95% CI 1.6-5.0; P < 0.001), 4 months (WMD 7.3; 95% CI 3.4-11.2; P < 0.001), and 6 months (WMD 4.6; 95% CI 3.3-5.8; P < 0.001) postoperatively. Patients with cemented hemiarthroplasty had lower rates of pain (RR 0.59; 95% CI 0.39-0.9; P = 0.013), prosthetic fracture (RR 0.24; 95% CI 0.16-0.38; P < 0.001), subsidence/loosening (RR 0.29; 95% CI 0.11-0.78; P = 0.014), revisions (RR 0.59; 95% CI 0.40-0.89; P = 0.012), and pressure ulcers (RR 0.43; 95% CI 0.23-0.82; P = 0.01) at the expense of longer surgery time (WMD 7.87; 95% CI 5.71-10.02; P < 0.001). CONCLUSION: This meta-analysis demonstrated that patients with cemented hemiarthroplasty had better results in hip function and pain relief and lower complication rates at the expense of prolonged surgery time. Cemented hemiarthroplasty is recommended based on our findings.

[Emulsion liquid membrane extraction with D2EHPA mobile carrier Hirudinaria manillensis hirudin in experimental study].

OBJECTIVE: To study the extraction system of hirudin emulsion liquid membrane with the Poecilobdella manillensis as raw material, di-(2-ethylhexyl) phosphate (D2EHPA) as carrier, Span 80 as emulsifier, octane and D2EHPA mixed to constitute membrane solution, diluted HCl solutions as internal aqueous phase. METHOD: Using the orthogonal experiment to optimize the extraction conditions of hirudin reference substance such as membrane phase, internal aqueous phase volume ratio (MIPVR), external aqueous phase pH, internal aqueous phase pH, mobile carrier concentration and so on, and then using hirudin crude extracts to do purifying experiment, and gaining experimental samples. RESULT: The optimal conditions of hirudin extraction were as follows: MIPVR 10: 3, internal aqueous phase pH 2.6, external aqueous phase pH 3.4, the mass fraction of carrier D2EHPA 2%. In the optimal extraction conditions, when the initial concentration of hirudin was one anti-thrombin activity units (ATU) x mL(-1), ATU recovery rate of the reference substance was 83.06%. In the purifying experiment of crude extracts, ATU recovery rate was 82.99%, and the specific activity of sample was 3 289.48 the ATU x mg(-1). Discontinuous polyacrylamide gel electrophoresis and spectral scanning, the results showed that the purity and reference substance were considerable. CONCLUSION: The method of preparation hirudin was relatively simple, the purity of the experimental samples and ATU recovery were both high.

Comparison of procedural, clinical and valve performance results of transcatheter aortic valve replacement in patients with bicuspid versus tricuspid aortic stenosis.

BACKGROUND: Limited date describing the procedural, clinical and valve performance results of transcatheter aortic valve replacement (TAVR) in patients with bicuspid versus tricuspid aortic stenosis (TAV). METHODS: Procedural and clinical results were defined and reported according to VARC-2 criteria. RESULTS: Consecutive 87 patients with BAV and 70 patients with TAV were included. Compared to patients with TAV, patients with BAV had similar incidence of second valve implantation (14.9% vs 12.9%, p=0.708), more than mild paravalvular leakage (PVL, 40.2% vs 31.9%, p=0.288), permanent pacemaker implantation (PPM, 24.1% vs 28.6%, p=0.53). Furthermore, the procedural and clinical results of TAVR also did not differ between patients with type 0 and type 1 (second valve implantation: 18.4% vs 11.8%, p=0.71, PVL: 38.8% vs 41.2%, p=0.83, PPM: 18.4% vs 31.6%, p=0.16). The hemodynamic outcomes were similar in patients with BAV and TAV at 1-year (maximum velocity, 2.3 vs 2.2m/s, p=0.307) and 2-year (2.3 vs 2.1m/s, p=0.184) follow-up respectively. Adjusted binary logistic regression analysis found oversizing ratio at 14.45-20.57% is at lower risk for more than mild PVL (OR, 0.069, 95% CI, 0.011-0.428, p=0.004). Moreover, the Kaplan-Meier survival analysis revealed that TAVR in type 0 BAV, type 1 BAV and TAV have comparable risk for midterm mortality (Log rank, p=0.772). CONCLUSION: TAVR in whatever type of BAV appeared to be safe and efficacy, and TAVR in BAV was associated with comparable bioprosthetic function during follow up compared to patients with TAV.

Dickkopf-related protein 3 negatively regulates the osteogenic differentiation of rat dental follicle cells.

The present study aimed to investigate the effect of Dickkopf-related protein 3 (DKK3) on osteogenic differentiation of rat dental follicle cells (DFCs). A PCR array analysis of Wnt pathway activation in DFCs identified genes dysregulated by mineral induction. Among them, DKK3expression levels were decreased, and further experiments were conducted to investigate its role in DFC osteogenesis. By comparing DFCs grown in normal growth and mineral­induction media for 4 weeks, the present study confirmed that DKK3 was a potential target gene of osteogenesis through reverse transcription-quantitative polymerase chain reaction (RT­qPCR) and western blotting (WB). A short hairpin RNA (shRNA) was introduced into DFCs using a lentiviral vector to inhibit DKK3 expression. An alkaline phosphatase (ALP) activity assay and Alizarin Red staining were performed to observe the DKK3­shRNA DFCs. In addition, the osteogenic differentiation of DKK3­shRNA DFCs was analyzed by RT­qPCR and WB. In vivo, DKK3­shRNA DFCs seeded on hydroxyapatite/ß-tricalcium phosphate (HA/TCP) scaffolds were transplanted into the subcutaneous tissue of mice with severe combined immunodeficiency, followed by hematoxylin­eosin and Masson staining. The results confirmed that DKK3 expression was downregulated during mineral induction in rat DFCs. Lentivirus­mediated expression of DKK3 shRNA in DFCs promoted calcified­nodule formation, ALP activity and the expression of ß­catenin, runt­related transcription factor 2 and osteocalcin, compared with control cells. In vivo, the implanted section presented the majority of newly formed osteoid matrices and collagen, with limited space between the HA/TCP scaffolds and matrices. In conclusion, DKK3 expression negatively regulates the osteogenic differentiation of DFCs and, conversely, downregulation of DKK3 may enhance DFC osteogenesis.

Organic Photovoltaics and Bioelectrodes Providing Electrical Stimulation for PC12 Cell Differentiation and Neurite Outgrowth.

Current bioelectronic medicines for neurological therapies generally involve treatment with a bioelectronic system comprising a power supply unit and a bioelectrode device. Further integration of wireless and self-powered units is of practical importance for implantable bioelectronics. In this study, we developed biocompatible organic photovoltaics (OPVs) for serving as wireless electrical power supply units that can be operated under illumination with near-infrared (NIR) light, and organic bioelectronic interface (OBEI) electrode devices as neural stimulation electrodes. The OPV/OBEI integrated system is capable to provide electrical stimulation (ES) as a means of enhancing neuron-like PC12 cell differentiation and neurite outgrowth. For the OPV design, we prepared devices incorporating two photoactive material systems--ß-carotene/N,N'-dioctyl-3,4,9,10-perylenedicarboximide (ß-carotene/PTCDI-C8) and poly(3-hexylthiophene)/phenyl-C61-butyric acid methyl ester (P3HT/PCBM)--that exhibited open circuit voltages of 0.11 and 0.49 V, respectively, under NIR light LED (NLED) illumination. Then, we connected OBEI devices with different electrode gaps, incorporating biocompatible poly(hydroxymethylated-3,4-ethylenedioxythiophene), to OPVs to precisely tailor the direct current electric field conditions during the culturing of PC12 cells. This NIR light-driven OPV/OBEI system could be engineered to provide tunable control over the electric field (from 220 to 980 mV mm(-1)) to promote 64% enhancement in the neurite length, direct the neurite orientation on chips, or both. The OPV/OBEI integrated systems under NIR illumination appear to function as effective power delivery platforms that should meet the requirements for wirelessly offering medical ES to a portion of the nervous system; they might also be a key technology for the development of next-generation implantable bioelectronics.

[Detection of periodontal pathogens from saliva of type 2 diabetic patients in urban area of Beijing].

OBJECTIVE: To investigate the prevalence of periodontal pathogens from saliva of patients with type 2 diabetes mellitus (T2DM), and to characterize the association between the glucose status and periodontal pathogens in oral cavity. METHODS: All the subjects were hypertension patients under regular care at Beijing hypertension prevention and management institute. Whole unstimulated saliva samples were collected from 45 non-diabetic subjects (non-DM group), 80 well-controlled diabetic patients (DM-well group) and 100 poor-controlled diabetic patients (DM-poor group). DNA was extracted from the salivary deposition, Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf) and Treponema denticola (Td) were detected by polymerase chain reaction (PCR) method based on 16SrRNA. Prevalence and quantity of the pathogens under different glucose states were compared and logistic regression model was set to analyze the factors related to each bacterium. RESULTS: The prevalence of Tf in DM-well group and DM-poor group was significantly lower than that of non-DM group [81% (65/80), 80% (80/100) vs 91% (41/45), P = 0.048], meanwhile the quantity of Tf was also lower than that of non-DM group [1.9(2.6), 2.1(5.3) vs 3.4(6.4)] (P > 0.05). With the worsening of glucose control, the quantity of Tf was declining (P = 0.032). However, the prevalence and the quantity of Pg, Td in 3 groups had no statistical differences (P > 0.05). After adjusting age, gender, number of missing teeth and other periodontal parameters, OR of having Tf in saliva from DM-well group and DM-poor group was 0.58 and 0.53, respectively. CONCLUSIONS: Abnormal blood glucose state may affect the colonization of Tf in oral cavity.

Responsiveness of voltage-gated calcium channels in SH-SY5Y human neuroblastoma cells on quasi-three-dimensional micropatterns formed with poly (l-lactic acid).

INTRODUCTION: In this study, quasi-three-dimensional (3D) microwell patterns were fabricated with poly (l-lactic acid) for the development of cell-based assays, targeting voltage-gated calcium channels (VGCCs). METHODS AND MATERIALS: SH-SY5Y human neuroblastoma cells were interfaced with the microwell patterns and found to grow as two dimensional (2D), 3D, and near two dimensional (N2D), categorized on the basis of the cells' location in the pattern. The capability of the microwell patterns to support 3D cell growth was evaluated in terms of the percentage of the cells in each growth category. Cell spreading was analyzed in terms of projection areas under light microscopy. SH-SY5Y cells' VGCC responsiveness was evaluated with confocal microscopy and a calcium fluorescent indicator, Calcium Green™-1. The expression of L-type calcium channels was evaluated using immunofluorescence staining with DM-BODIPY. RESULTS: It was found that cells within the microwells, either N2D or 3D, showed more rounded shapes and less projection areas than 2D cells on flat poly (l-lactic acid) substrates. Also, cells in microwells showed a significantly lower VGCC responsiveness than cells on flat substrates, in terms of both response magnitudes and percentages of responsive cells, upon depolarization with 50 mM K(+). This lower VGCC responsiveness could not be explained by the difference in L-type calcium channel expression. For the two patterns addressed in this study, N2D cells consistently exhibited an intermediate value of either projection areas or VGCC responsiveness between those for 2D and 3D cells, suggesting a correlative relation between cell morphology and VGCC responsiveness. CONCLUSION: These results suggest that the pattern structure and therefore the cell growth characteristics were critical factors in determining cell VGCC responsiveness and thus provide an approach for engineering cell functionality in cell-based assay systems and tissue engineering scaffolds.

Microfluidic pool structure for cell docking and rapid mixing.

A microfluidic pool structure for cell docking and rapid mixing is described. The pool structure is defined as a microchamber on one structural layer of a bilayer chip and connects with two or more individual microchannels on the other structural layer. In contrast to the turbulent flow in a macroscale pool, laminar streams enter and exit this microfluidic pool structure with definite and controllable direction that may be influenced by the location and geometry of the pool. A simple microfluidic model was used to validate this hypothesis. In this model, a microscale pool structure was made on the lower layer of a chip and connected with three parallel microchannels in the upper layer. Simulation and experimental results indicated that the flow profile within the pool structure was determined by its geometry and location. This could be used as a flow control method and it was simpler than designs based on microvalve, hydraulic pressure, or electrokinetic force, and has some important applications. For example, controllable streams within this structure were used to immobilize biological cells along the microchannel walls. When different solution streams flowed through the pool, rapid diffusion of analytes occurred for short diffusion distance between vertical flow laminas. Furthermore, desired dilution (mixing) ratio could be obtained by controlling the geometry of the microfluidic pool.