Human aortic endothelial cell response to 316L stainless steel material microstructure.

The role of metal microstructure (e.g. grain sizes) in modulating cell adherence behavior is not well understood. This study investigates the effect of varying grain sizes of 316L stainless steel (SS) on the attachment and spreading of human aortic endothelial cells (HAECs). Four different grain size samples; from 16 to 66 microm (ASTM 9.0-4.9) were sectioned from sheets. Grain structure was revealed by polishing and etching with glycergia. Contact angle measurement was done to assess the hydrophilicity of the specimens. Atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) were used to characterize the roughness and surface chemistry of the specimens. Cells were seeded on mechanically polished and chemically etched specimens followed by identification of activated focal adhesion sites using fluorescently tagged anti-pFAK (phosphorylated focal adhesion kinase). The 16 microm grain size etched specimens had significantly (P < 0.01) higher number of cells attached per cm(2) than other specimens, which may be attributed to the greater grain boundary area and associated higher surface free energy. This study shows that the underlying material microstructure may influence the HAEC behavior and may have important implications in endothelialization.

Long-term stability of self-assembled monolayers on electropolished L605 cobalt chromium alloy for stent applications.

Commercially available drug-eluting stents have the potential to induce inflammatory and hypersensitive adverse reactions due to their polymer coating. The use of self assembled monolayers (SAMs) as an alternate drug delivery platform for stents has recently been demonstrated. In this study, the formation and stability of phosphonic acid SAMs were investigated using the material and surface preparation commonly used to make ultra-thin stent struts-electropolished L605 Cobalt Chromium (CoCr) alloy. Methyl (⁻CH3) and carboxylic acid (⁻OOH) terminated phosphonic acid SAMs were coated on electropolished CoCr alloy using a combination of solution immersion and dip-evaporation cycle deposition methods. SAMs-coated CoCr alloy specimens were thoroughly characterized using contact angle goniometry, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). These characterizations suggested that uniform and well-ordered monolayers were coated on the electropolished CoCr alloy. The long-term physiological stability of monolayers was investigated in tris-buffered saline (TBS) at 37°C for up to 28 days. Contact angles, FTIR, XPS, and AFM suggested that both ⁻CH3 and ⁻COOH terminated phosphonic acid SAMs desorb from electropolished CoCr alloy surfaces in a biphasic manner. A significant desorption of ⁻CH3 and ⁻COOH terminated SAMs occurs within 1-3 days followed by a slower desorption for up to 28 days. Thus, there is a need to develop techniques that can improve the long-term stability of SAMs on electropolished CoCr alloy for stent and other biomedical applications.

Delivery of paclitaxel from cobalt-chromium alloy surfaces without polymeric carriers.

Polymer-based carriers are commonly used to deliver drugs from stents. However, adverse responses to polymer coatings have raised serious concerns. This research is focused on delivering drugs from stents without using polymers or any carriers. Paclitaxel (PAT), an anti-restenotic drug, has strong adhesion towards a variety of material surfaces. In this study, we have utilized such natural adhesion property of PAT to attach these molecules directly to cobalt-chromium (Co-Cr) alloy, an ultra-thin stent strut material. Four different groups of drug coated specimens were prepared by directly adding PAT to Co-Cr alloy surfaces: Group-A (PAT coated, unheated, and ethanol cleaned); Group-B (PAT coated, heat treated, and ethanol cleaned); Group-C (PAT coated, unheated, and not ethanol cleaned); and Group-D (PAT coated, heat treated and not ethanol cleaned). In vitro drug release of these specimens was investigated using high performance liquid chromatography. Groups A and B showed sustained PAT release for up to 56 days. A simple ethanol cleaning procedure after PAT deposition can remove the loosely bound drug crystals from the alloy surfaces and thereby allowing the remaining strongly bound drug molecules to be released at a sustained rate. The heat treatment after PAT coating further improved the stability of PAT on Co-Cr alloy and allowed the drug to be delivered at a much slower rate, especially during the initial 7 days. The specimens which were not cleaned in ethanol, Groups C and D, showed burst release. PAT coated Co-Cr alloy specimens were thoroughly characterized using scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. These techniques were collectively useful in studying the morphology, distribution, and attachment of PAT molecules on Co-Cr alloy surfaces. Thus, this study suggests the potential for delivering paclitaxel from Co-Cr alloy surfaces without using any carriers.

Drug delivery from gold and titanium surfaces using self-assembled monolayers.

Currently available drug-eluting stents (DES) use polymers for coating and releasing drugs. Increasing evidence suggests that inflammatory and hypersensitive reactions are caused by such polymer coatings. This study focused on developing new techniques for delivering drugs directly from metal implant surfaces. Hydroxyl-terminated self-assembled monolayers (SAMs) were coated on Au and Ti surfaces. Therapeutic self-assembled monolayers (TSAMs) were prepared by chemically attaching the model drug, flufenamic acid, to SAM coated metal surfaces. Three different methods of esterification (acid chloride esterification, dry heat esterification, and direct esterification) were explored to attach flufenamic acid to SAMs. TSAMs were characterized using X-ray photoelectron spectroscopy, fluorescence microscopy, atomic force microscopy, and contact angle goniometry. These techniques collectively confirmed the attachment of drug onto SAM coated metal surfaces. In vitro drug release was investigated by immersing TSAM coated metal specimens in tris-buffered saline (TBS) at 37 degrees C for 28 days. TBS was analyzed at 1, 3, 7, 14, 21, and 28 days for the amount of drug eluted using high performance liquid chromatography. Large data scatter was observed for the release profiles of TSAMs prepared by acid chloride esterification. TSAMs prepared by dry heat and direct esterification methods showed an initial burst release of the drug followed by a sustained slow release for up to 2 weeks. Thus, this study suggests the potential for using self-assembled monolayers as an alternate system for delivering drugs from coronary stents and other metal implants.

Drug loading of nanoporous TiO2 films.

The loading of therapeutic amounts of drug on a nanoporous TiO(2) surface is described. This novel drug-loading scheme on a biocompatible surface, when employed on medical implants, will benefit patients who require the deployment of drug-eluting implants. Anticoagulants, analgesics and antibiotics can be considered on the associated implants for drug delivery during the time of maximal pain or risk for patients undergoing orthopedic procedures. Therefore, this scheme will maximize the chances of patient recovery.

Influence of stent design and material composition on procedure outcome.

Although intravascular stents have received widespread application, significant limitations remain. In stent restenosis, the most pervasive problem affecting stents, is related in part to technical aspects of the device. Design features of the stent that influence outcome have been identified and optimized for improved performance. The influence of stent materials on critical aspects of healing, such as thrombotic, inflammatory, and hyperplastic responses, are less well understood. For this reason, significant progress in this area is lacking. Current stents have significant contamination with industrial impurities on the surface and in the bulk. This fact adds to the difficulties in interpreting the biologic reaction of the host to the device. Better understanding of the basic biologic interactions is the path to significant improvement.