Enhanced biocompatibility of Nitinol via surface treatment and alloying

It is projected that by 2020, there will be 138 million Americans over 45, the age at which the increased incidence of heart diseases is documented. Many will require stents. This multi-billion dollar industry, with over 2 million patients worldwide, 15% of whom use Nitinol stents have experienced a decline in sales recently, due in part to thrombosis. It is a sudden blood clot that forms inside stents. As a result, the Food and Drug Administration and American Heart Association are calling for a new generation of stents, new designs and different alloys that are more adaptable to the arteries. The future of Nitinol therefore depends on a better understanding of the mechanisms by which Nitinol surfaces can be rendered stable and inert. In this investigation, binary and ternary Nitinol alloys were prepared and subjected to various surface treatments such as electropolishing (EP), magnetoelectropolishing (MEP) and water boiling & passivation (W&P). In vitro corrosion tests were conducted on Nitinol alloys in accordance with ASTM F 2129-08. The metal ions released into the electrolyte during corrosion tests were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). Biocompatibility was assessed by observing the growth of human umbilical vein endothelial cells (HUVEC) on the surface of Nitinol alloys. Static and dynamic immersion tests were performed by immersing the Nitinol alloys in cell culture media and measuring the amount of metal ions released in solution. Sulforhodamine B (SRB) assays were performed to elucidate the effect of metal ions on the growth of HUVEC cells. The surfaces of the alloys were studied using Scanning Electron Microscopy (SEM) and X-ray Photoelectron Spectroscopy (XPS) respectively. Finally, wettability and surface energy were measured by Contact Angle Meter, whereas surface roughness was measured by Atomic Force Microscopy (AFM). All the surface treated alloys exhibited high resistance to corrosion when compared with untreated alloys. SRB assays revealed that Ni and Cu ions exhibited greater toxicity than Cr, Ta and Ti ions on HUVEC cells. EP and MEP alloys possessed relatively smooth surfaces and some were composed of nickel oxides instead of elemental nickel as determined by XPS. MEP exhibited lowest surface energy and lowest surface roughness.

Enhanced Biocompatibility of NiTi (Nitinol) Via Surface Treatment and Alloying

It is projected that by 2020, there will be 138 million Americans over 45, the age at which the increased incidence of heart diseases is documented. Many will require stents. This multi-billion dollar industry, with over 2 million patients worldwide, 15% of whom use Nitinol stents have experienced a decline in sales recently, due in part to thrombosis. It is a sudden blood clot that forms inside stents. As a result, the Food and Drug Administration and American Heart Association are calling for a new generation of stents, new designs and different alloys that are more adaptable to the arteries. The future of Nitinol therefore depends on a better understanding of the mechanisms by which Nitinol surfaces can be rendered stable and inert. In this investigation, binary and ternary Nitinol alloys were prepared and subjected to various surface treatments such as electropolishing (EP), magnetoelectropolishing (MEP) and water boiling & passivation (W&P). In vitro corrosion tests were conducted on Nitinol alloys in accordance with ASTM F 2129-08. The metal ions released into the electrolyte during corrosion tests were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). Biocompatibility was assessed by observing the growth of human umbilical vein endothelial cells (HUVEC) on the surface of Nitinol alloys. Static and dynamic immersion tests were performed by immersing the Nitinol alloys in cell culture media and measuring the amount of metal ions released in solution. Sulforhodamine B (SRB) assays were performed to elucidate the effect of metal ions on the growth of HUVEC cells. The surfaces of the alloys were studied using Scanning Electron Microscopy (SEM) and X-ray Photoelectron Spectroscopy (XPS) respectively. Finally, wettability and surface energy were measured by Contact Angle Meter, whereas surface roughness was measured by Atomic Force Microscopy (AFM). All the surface treated alloys exhibited high resistance to corrosion when compared with untreated alloys. SRB assays revealed that Ni and Cu ions exhibited greater toxicity than Cr, Ta and Ti ions on HUVEC cells. EP and MEP alloys possessed relatively smooth surfaces and some were composed of nickel oxides instead of elemental nickel as determined by XPS. MEP exhibited lowest surface energy and lowest surface roughness.

Specific Increase in MDR1 Mediated Drug-Efflux in Human Brain Endothelial Cells following Co-Exposure to HIV-1 and Saquinavir

Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain Barrier (BBB) which interferes with anti-HIV drug delivery into the CNS. The ATP binding cassette (ABC) transporters expressed on HBMVEC can efflux HIV-1 protease inhibitors (HPI), enabling the persistence of HIV-1 in CNS. Constitutive low level expression of several ABC-transporters, such as MDR1 (a.k.a. P-gp) and MRPs are documented in HBMVEC. Although it is recognized that inflammatory cytokines and exposure to xenobiotic drug substrates (e.g HPI) can augment the expression of these transporters, it is not known whether concomitant exposure to virus and anti-retroviral drugs can increase drug-efflux functions in HBMVEC. Our in vitro studies showed that exposure of HBMVEC to HIV-1 significantly up-regulates both MDR1 gene expression and protein levels; however, no significant increases in either MRP-1 or MRP-2 were observed. Furthermore, calcein-AM dye-efflux assays using HBMVEC showed that, compared to virus exposure alone, the MDR1 mediated drug-efflux function was significantly induced following concomitant exposure to both HIV-1 and saquinavir (SQV). This increase in MDR1 mediated drug-efflux was further substantiated via increased intracellular retention of radiolabeled [3H-] SQV. The crucial role of MDR1 in 3H-SQV efflux from HBMVEC was further confirmed by using both a MDR1 specific blocker (PSC-833) and MDR1 specific siRNAs. Therefore, MDR1 specific drug-efflux function increases in HBMVEC following co-exposure to HIV-1 and SQV which can reduce the penetration of HPIs into the infected brain reservoirs of HIV-1. A targeted suppression of MDR1 in the BBB may thus provide a novel strategy to suppress residual viral replication in the CNS, by augmenting the therapeutic efficacy of HAART drugs.

Characterization of engineered human lung tissue

Characterizing engineered human lung tissue is an important step in developing a functional tissue replacement for lung tissue repair and in vitro analysis. Small tissue constructs were grown by seeding IMR-90 fetal lung fibroblasts and adult microvascular endothelial cells onto a Polyglycolic acid (PGA) polymer template. Introducing the constructs to dynamic culture conditions inside a bioreactor facilitated three-dimensional growth seen in scanning electron microscopy images (SEM). Characterization of the resultant tissue samples was done using SEM imagery, tensile tests, and biochemical assays to quantify extra-cellular matrix (ECM) composition. Tensile tests of the engineered samples indicated an increase in the mechanical properties when compared with blank constructs. Elastin and collagen content was found to average 3.19% and 15.49% respectively in relation to total mass of the tissue samples. The presence of elastin and collagen within the constructs most likely explains the mechanical differences that we noted. These findings suggest that the necessary ECM can be established in engineered tissue constructs and that optimization of this procedure has the capacity to generate the load bearing elements required for construction of a functional lung tissue equivalent.