In this investigation we studied the efficacy and durability of recombinant adeno-associated virus serotype 9 (rAAV9) vector-mediated gene transfer to the transplanted rat heart.
A rAAV9-CMV-lacZ ...vector diluted in cold (4 degrees C) University of Wisconsin solution was used to perfuse the rat coronary vasculature for 20 minutes prior to syngeneic heterotopic transplantation. Perfusion experiments (six groups, n = 3/group) were performed without rAAV9 and at four separate doses ranging from 2 x 10(9) to 2 x 10(12) viral genomes/ml. The transplanted heart was recovered 10 days or 3 months after transplantation and expression of lacZ assessed by histology, enzyme-linked immunoassay and real-time reverse transcript-polymerase chain reaction (RT-PCR). In a final group (n = 3), rAAV9 was administered systemically to compare the cardiac transduction efficiency and viral distribution to other organs.
Transduction efficiency of perfused virus correlated with vector dose (p < 0.0001), with myocardial transduction ranging up to 71.74% at the highest dose. Cardiac expression of lacZ was equivalent at 10 days and 3 months. There was no evidence of viral gene transfer to other organs after heart transplantation.
Our findings demonstrate efficient and durable rAAV9-mediated gene transfer to the transplanted heart after ex vivo perfusion and suggest that AAV9 is a promising vector for cardiac gene therapy.
PEDOT (Poly(3,4‐ethylenedioxythiophene)) is one of the most promising electrode materials for biomedical applications like neural recording and stimulation, thanks to its enhanced biocompatibility ...and electronic properties. Drug delivery by PEDOT is typically achieved by incorporating drugs as dopants during the electrodeposition procedure and a subsequent release can be promoted by applying a cathodic trigger that reduces PEDOT while enabling the drug to diffuse. This approach has several disadvantages including, for instance, the release of contaminants mainly due to PEDOT decomposition during electrochemical release. Herein we describe a new strategy based on the formation of a chemical linkage between the drug and the conductive polymer. In particular, dexamethasone was successfully integrated into a new electropolymerized PEDOT–Dex composite, leading to a self‐adjusting drug release system based on a biochemically hydrolysable bond between dexamethasone and PEDOT.
Let's make it self‐releasing: For several years the delivery of bioactive molecules, including Dexamethasone, from conductive polymers has been based on the “ionic‐approach”, which needs an external electrochemical trigger. Our new protocol, based on the chemical conjugation of Dexamethasone to the PEDOT backbone, enables a biochemically controlled release of Dexamethasone in response to the inflammation of the surrounding tissue.
The aim of the present study is to describe our preliminary experience with the Arrow CorAide left ventricular assist system (LVAS).
The Arrow CorAide LVAS is a small implantable, continuous flow ...centrifugal pump, with a fully suspended rotating assembly, intended as a bridge to transplant device, bridge to recovery, and for long-term use.
Since April 2005 we have implanted the CorAide LVAS in 2 male patients, with a patient follow-up of more than 6 months. Surgical procedures were uneventful, and both patients had an uneventful postoperative course, with fast weaning from mechanical ventilation and inotropic support. No thromboembolic events, infective complication, hemolysis, or mechanical failure occurred. To date, both patients are in New York Heart Association class I.
In our initial experience the CorAide LVAS blood pump is nonthrombogenic, nonhemolytic, and easy to implant. Both patients have improved their functional status. Further follow-up is needed to assess long-term results.
Simple fabrication, high power-to-weight and power-to-volume ratios, and the ability to operate in open air at low voltage make the ionic electroactive polymer actuators highly attractive for haptic ...applications. Whenever a direct tactile stimulation of the skin is involved, electrical and chemical insulation as well as a long-term stability of the actuator are required. Because of its inherent physicochemical properties such as high dielectric strength, resistance to solvents, and biological inactivity, Parylene C meets the requirements for making biocompatible actuators. We have studied the displacement and the generated force of Parylene-coated carbon nanotube actuators as well as the encapsulation quality. A 2 μm coating creates an effective electrical insulation of the actuators without altering the blocking force at frequencies from 50 mHz to 1 Hz. Moreover, the generated strain is preserved at higher frequencies (from 0.5 to 5 Hz). We employed a simple mechanical model to explain the relation between the key parametersflexural stiffness, displacement, and forcefor uncoated and coated actuators. In addition, we demonstrated that our Parylene-coated actuators are not damaged by rinsing in liquid media such as 2-propanol or water. In conclusion, our results indicate that Parylene C encapsulated actuators are safe to touch and can be used in contact with human skin and in biomedical applications in direct contact with tissues and physiological fluids.
We report on the identification of efficient combinations of catalyst, carbon feedstock, and temperature for the ethanol chemical vapour deposition (CVD) growth of single-wall carbon nanotubes ...(SWCNTs) onto silicon substrates.
Different catalyst preparations, based on organometallic salts (Co, Fe, Mo, Ni acetate, and bimetallic mixtures), have been spin coated onto thermally grown silicon dioxide on silicon chips to perform tests in a temperature range between 500 and 900
°C.
The samples have been then characterized by Raman spectroscopy, atomic force microscopy, scanning electron microscopy, and transmission electron microscopy. Assuming the growth of high-quality isolated nanotubes as target, the ratio in Raman spectra between the intensity of the
G peak and of the
D peak has been used as the main parameter to evaluate the performance of the catalytic process. A comparison made for both single metals and bimetallic mixtures points out best conditions to achieve efficient CVD growth of SWCNTs.
Localized drug delivery represents one of the most challenging uses of systems based on conductive polymer films. Typically, anionic drugs are incorporated within conductive polymers through ...electrostatic interaction with the positively charged polymer. Following this approach, the synthetic glucocorticoid dexamethasone phosphate is often delivered from neural probes to reduce the inflammation of the surrounding tissue. In light of the recent literature on the neuroprotective and anti‐inflammatory properties of tauroursodeoxycholic acid (TUDCA), for the first time, this natural bile acid was incorporated within poly(3,4‐ethylenedioxythiophene) (PEDOT). The new material, PEDOT—TUDCA, efficiently promoted an electrochemically controlled delivery of the drug, while preserving optimal electrochemical properties. Moreover, the low cytotoxicity observed with viability assays, makes PEDOT–TUDCA a good candidate for prolonging the time span of chronic neural recording brain implants.
From bears to brain: The Food and Drug Administration approved hydrophilic bile acid tauroursodeoxycholic acid (TUDCA) was successfully incorporated in electrodeposited PEDOT films. This study was aimed at the realization of a new PEDOT–TUDCA composite material that may result a potential substitute of the synthetic glucocorticoids for localized drug delivery system in neuroscience applications.
Minimally invasive cardiac surgery (MICS) has constantly evolved over the past years, and new technologies have been introduced. The aims of this study were to analyze the evolution of our 10-year ...experience in MICS and to highlight outcomes in different spans of time.
Patients undergoing MICS for mitral valve, tricuspid valve, and/or atrial septal defect or atrial masses from November 2005 to November 2015 were retrospectively analyzed. A comparative analysis was performed by identifying 2 groups: the control group (in the first time span of our experience) and the tailored group (patients who underwent surgery after a full preoperative anatomic evaluation with allocation to the proper setting).
During the study period 971 patients underwent MICS. MICS procedures increased from 44% in 2006 to 96% in 2015. Subgroup analysis revealed a significant decrease in the rate of procedures performed with retrograde arterial perfusion (99.1% vs 91.7%, P < .0001), a significant increase in the rate of complex mitral valve procedures (22.4% vs 7.9%, P < .0001), and a significant decrease in the rate of stroke (from 5.2% to 1%, P < .001) in the tailored group. The logistic regression analysis showed that the tailored approach was a protective factor against neurologic complications.
The present study shows the considerable and attractive results of our decision-making process based on the tailored approach. The 10-year outcome analysis demonstrated a trend toward a progressive decrease in the overall rate of postoperative complications and a significant protective effect of the tailored approach on the occurrence of stroke.
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