In vivo Evaluation of Cenderitide-Eluting Stent (CES) II.

The use of drug-eluting coronary stents has led to significant reduction in in-stent restenosis (ISR), but led to delayed endothelialization, necessitating the prolonged use of expensive anti-thrombotic drugs with their side-effects. Cenderitide (CD-NP) is a novel anti-proliferative chimeric peptide of semi-endothelial origin. Our previous work in vitro has demonstrated; that the smooth muscle cells were inhibited significantly more than endothelial cells which is the desirable feature of an anti-restenosis drug. This work reports the effects of implantation of a centeritide-eluting stent (CES) on ISR and endothelialization in an in vivo model. CESs were produced by coating bare metallic stents with CD-NP entrapped in biodegradable poly(ε-caprolactone) using an ultrasonic spray coater. A total of 32 stents were successfully implanted into 16 pigs, and all animal survived for 28 days. The plasma levels of CD-NP were significantly higher in the CES group than in the control group (bare metal stents and polymer-coated stent) at post-stenting, indicating the successful release of CD-NP from the stent in vivo. Furthermore, SEM analysis results showed the greater endothelial coverage of the stent struts, as well as between the struts in CES group. Moreover, histological results showed mild inflammation, and low fibrin score at 28 days. However, plasma cGMP (second messenger, cyclic 3',5' guanosine monophosphate) does not show a significant difference, and the CES is also unable to show significant difference in terms on neointimal area and stenosis, in comparison to BMS at 28 days.

Pushing the envelope in tissue engineering: ex vivo production of thick vascularized cardiac extracellular matrix constructs.

Functional vascularization is a prerequisite for cardiac tissue engineering of constructs with physiological thicknesses. We previously reported the successful preservation of main vascular conduits in isolated thick acellular porcine cardiac ventricular ECM (pcECM). We now unveil this scaffold's potential in supporting human cardiomyocytes and promoting new blood vessel development ex vivo, providing long-term cell support in the construct bulk. A custom-designed perfusion bioreactor was developed to remodel such vascularization ex vivo, demonstrating, for the first time, functional angiogenesis in vitro with various stages of vessel maturation supporting up to 1.7 mm thick constructs. A robust methodology was developed to assess the pcECM maximal cell capacity, which resembled the human heart cell density. Taken together these results demonstrate feasibility of producing physiological-like constructs such as the thick pcECM suggested here as a prospective treatment for end-stage heart failure. Methodologies reported herein may also benefit other tissues, offering a valuable in vitro setting for "thick-tissue" engineering strategies toward large animal in vivo studies.

n-Type carbon nanotubes/silver telluride nanohybrid buckypaper with a high-thermoelectric figure of merit.

n-Type thermoelectric (TE) materials was made from carbon nanotube (CNT) buckypapers. We used silver telluride (Ag2Te) to achieve electron injection to the CNTs. The TE characterizations on more than 50 samples show that the CNTs/Ag2Te hybrids exhibit negative Seebeck coefficients (e.g., n-type) from -30 to -228 µV/K. Meanwhile, the tunneling coupling between the CNTs and Ag2Te increase the electrical conductance to the range of 10,000-20,000 S/m, which is higher than each single component (CNTs or Ag2Te). These n-type TE buckypapers are flexible and robust with ZT values of 1-2 orders of magnitude higher than previously reproted for CNT-based TE materials. In addition, the preparation of such buckypapers are very simple compared to a tranditonal inorganic process, without the need for hot pressing or spark sintering. These n-type TE buckypapers can provide important components for fabricating CNT-based flexible TE devices with good conversion efficiency.

Development of nanomaterials for SALDI-MS analysis in forensics.

Within the last decade, the escalation of research output in the field of nanotechnology has spurred the development of new nanomaterials for use as assisting agents in surface assisted laser desorption ionization mass spectrometry (SALDI-MS). Specifically modified nanomaterials, coupled with mass spectrometry, have improved the detection sensitivity, specificity, flexibility and reproducibility of SALDI-MS analysis. The technological advancement of LDI-MS has in turn, propelled the use of the analytical technique in the field of forensics. In this report, the various roles and applications of metal-, silicon- and carbon-based nanostructured materials as SALDI matrices in the analysis of forensic samples are described. The advantages of SALDI-MS as an analytical tool for forensic sample analysis are also discussed.

A carbon monoxide gas sensor using oxygen plasma modified carbon nanotubes.

Carbon monoxide (CO) is a highly toxic gas that can be commonly found in many places. However, it is not easily detected by human olfaction due to its colorless and odorless nature. Therefore, highly sensitive sensors need to be developed for this purpose. Carbon nanotubes (CNTs) have an immense potential in gas sensing. However, CNT-based gas sensors for sensing CO are seldom reported due to the lack of reactivity between CO and CNTs. In this work, O(2) plasma modified CNT was used to fabricate a CNT gas sensor. The plasma treated CNTs showed selectively towards CO, with the capability of sensing low concentrations of CO (5 ppm) at room temperature, while the pristine CNTs showed no response. UV spectra and oxygen reduction reaction provided evidence that the difference in sensing property was due to the elimination of metallic CNTs and enhancement of the oxygen reduction property.

Multiscale topological guidance for cell alignment via direct laser writing on biodegradable polymer.

Direct laser writing on biodegradable polymer to create microchannels for aligning cells is presented here. This technique offers the advantages of ease-of-manufacturing, ease-of-design, high-speed single-step fabrication, and noncontacting to the material. In this work, microchannels of 100 microm width, 100 microm depth, and 50 microm intervals were created on a biodegradable polymer film directly using a Ti-sapphire femtosecond pulsed laser. Multiscale topological features were achieved as a result of the laser beam-material interaction. These topological features were used to guide cell alignment in the microchannels. We present results on the morphology of poly(L-lactide-co-epsilon-caprolactone) copolymer micromachined by femtosecond laser and demonstrate the attachment and alignment of C2C12 myoblast cells in the microchannels. C2C12 cells exhibited favorable attachment in the channels after 1 day of seeding. High degree of alignment was observed after 4 days as cells proliferated into a confluent patch inside the channels. This work demonstrated the potential of wavy surface features combined with appropriate channel size for high-density cell alignment using direct laser writing. This method also offers the opportunity to incorporate multiscale topological guidance on other biodegradable polymer implants, such as vascular scaffolds and stents, which require directed cell organization.

Electrospinning of polyvinylidene difluoride with carbon nanotubes: synergistic effects of extensional force and interfacial interaction on crystalline structures.

Polyvinylidene difluoride (PVDF) solutions containing a very low concentration of single-walled carbon nanotubes (SWCNTs) and multiwalled carbon nanotubes (MWCNTs) of similar surface chemistry, respectively, were electrospun, and the nanofibers formed were collected using a modified rotating disk collector. The polymorphic behavior and crystal orientation of the nanofibers were studied using wide-angle X-ray diffraction and infrared spectroscopy, while the nanotube alignment and interfacial interactions in the nanofibers were probed by transmission electron microscopy and Raman spectroscopy. It is shown that the interfacial interaction between the SWCNTs and PVDF and the extensional force experienced by the nanofibers in the electrospinning and collection processes can work synergistically to induce highly oriented beta-form crystallites extensively. In contrast, the MWCNTs could not be well aligned along the nanofiber axis, which leads to a lower degree of crystal orientation.

Hydrolytic degradation of electron beam irradiated high molecular weight and non-irradiated moderate molecular weight PLLA.

The purpose of this study is to examine the hydrolytic degradation of electron beam irradiated ring-opening polymerized (ROP) poly(l-lactide) (PLLA-ir) and non-irradiated melt polycondensation polymerized poly(l-lactic acid) (PLLA-pc). It was observed that irradiation increases the hydrolytic degradation rate constant for ROP PLLA. This was due to a more hydrophilic PLLA-ir, as a result of irradiation. The degradation rate constants (k) of PLLA-ir samples were also found to be similar, regardless of the radiation dose, and an empirically formulated equation relating hydrolytic degradation time span to radiation dose was derived. The k value for PLLA-pc was observed to be lower than that for PLLA-ir, though the latter had a higher molecular weight. This was due to the difference in degradation mechanism, in which PLLA-ir undergoes end group scission, through a back- biting mechanism, during hydrolysis and thus a faster hydrolysis rate. Electron beam irradiation, though accelerates the degradation of PLLA, has been shown to be useful in accurately controlling the hydrolytic time span of PLLA. This method of controlling the hydrolytic degradation time was by far an easier task than through melt polycondensation polymerization. This would allow PLLA to be used for drug delivery purposes or as a temporary implant that requires a moderate time span (3-6 months).

Biodegradable stents with elastic memory.

This work reports, for the first time, the development of a fully biodegradable polymeric stent that can self-expand at body temperatures (approximately 37 degrees C), using the concept of elastic memory. This self-expansion is necessary in fully polymeric stents, to overcome the problem of elastic recoil following balloon expansion in a body vessel. Bi-layered biodegradable stent prototypes were produced from poly-L-lactic acid (PLLA) and poly glycolic acid (PLGA) polymers. Elastic memory was imparted to the stents by temperature conditioning. The thickness and composition of each layer in the stents are critical parameters that affect the rate of self-expansion at 37 degrees C, as well as the collapse strengths of the stents. The rate of self-expansion of the stents, as measured at 37 degrees C, exhibits a maximum with layer thickness. The Tg of the outer layer is another significant parameter that affects the overall rate of expansion.

Influence of electron-beam radiation on the hydrolytic degradation behaviour of poly(lactide-co-glycolide) (PLGA).

The purpose of this study is to examine the effect of electron-beam (e-beam) radiation on the hydrolytic degradation of poly(lactide-co-glycolide) (PLGA) films. PLGA films were irradiated and observed to undergo radiation-induced degradation through chain scission, as observed from a drop in its average molecular weight with radiation dose. Irradiated (5, 10 and 20 Mrad) and non-irradiated (0 Mrad) samples of PLGA were subsequently hydrolytically degraded in phosphate-buffered saline solution at 37.0 degrees C over a span of 12 weeks. It was observed that the natural logarithmic molecular weight (lnMn) of PLGA decreases linearly with hydrolytic degradation time. The rate of water uptake is higher for samples irradiated at higher radiation dose (e.g. 20 Mrad) and subsequently causing an earlier onset of mass loss. It is postulated that the increase in water uptake is due to the presence of more hydrophilic end groups, which results in the formation of microcavities because of an increase in osmotic pressure. A relationship between radiation dose and the rate of hydrolytic degradation of PLGA films, through its molecular weight was also established. This relationship allows a more accurate and precise control of the life span of PLGA through the use of e-beam radiation.

Effect of isothermal annealing on the hydrolytic degradation rate of poly(lactide-co-glycolide) (PLGA).

Isothermal crystallization through annealing at 115 degrees C was conducted to increase the degree of crystallinity of poly (lactide-co-glycolide) (PLGA). The maximum increase in the degree of crystallinity (approximately 21%) was achieved after 60 min of annealing. The crystal size/perfection was observed to increase with annealing time. The annealed PLGA films were then hydrolytically degraded in phosphate buffered saline solution of pH 7.4 at 37 degrees C for up to 150 days. Minimal mass loss was observed throughout the time investigated, suggesting that the samples were still in the first phase of degradation. The increase in the degree of crystallinity of the PLGA samples annealed at 15 and 30 min was found to retard their overall rate of hydrolytic degradation, when compared to those samples with higher initial crystallinity (annealed for 45 and 60 min) that had faster degradation rates. The increased degradation rate at higher crystallinity was associated with the loss of amorphous material and the formation of voids during annealing, which decreases the glass transition temperature and increases the average water uptake in the samples annealed for longer times. Therefore, the increase in degree of crystallinity is found to retard hydrolytic degradation but only to a certain extent, beyond which the formation of voids through annealing increases the rate of hydrolytic degradation.