Drug susceptibility of matrix-encapsulated Candida albicans nano-biofilms.

The rise in the use of biomedical devices and implants has seen a concomitant surge in the advent of device-related nosocomial (hospital-acquired) infections of bacterial and fungal origins. The most common nosocomial fungal infection is candidiasis caused mainly by Candida albicans biofilms. Candidiasis is associated with an unacceptably high mortality rate, and there is an urgent need for the discovery of new antifungal drugs that prevent or control biofilm formation. To this end, we recently developed an ultra-high-throughput microarray platform consisting of nano-scale biofilms of C. albicans encapsulated in collagen or alginate hydrogel matrices for antifungal drug screening. Here, we report that the choice of matrix influences the apparent susceptibility of C. albicans to the common antifungal drugs, amphotericin B, and caspofungin. While amphotericin B is equally effective against biofilms grown in collagen and alginate matrices, caspofungin is effective only against biofilms grown only in alginate, but not in collagen. We demonstrate differences in the distribution of the drugs in the two matrices may contribute to the susceptibility of C. albicans nano-biofilms. In a larger context, our results highlight the importance of the choice of matrix as a parameter in 3D cell encapsulation, and suggest a screening strategy to predict drug performance in vivo.

Preventing diabetic foot ulcer recurrence in high-risk patients: use of temperature monitoring as a self-assessment tool.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of a temperature monitoring instrument to reduce the incidence of foot ulcers in individuals with diabetes who have a high risk for lower extremity complications. RESEARCH DESIGN AND METHODS: In this physician-blinded, randomized, 15-month, multicenter trial, 173 subjects with a previous history of diabetic foot ulceration were assigned to standard therapy, structured foot examination, or enhanced therapy groups. Each group received therapeutic footwear, diabetic foot education, and regular foot care. Subjects in the structured foot examination group performed a structured foot inspection daily and recorded their findings in a logbook. If standard therapy or structured foot examinations identified any foot abnormalities, subjects were instructed to contact the study nurse immediately. Subjects in the enhanced therapy group used an infrared skin thermometer to measure temperatures on six foot sites each day. Temperature differences >4 degrees F (>2.2 degrees C) between left and right corresponding sites triggered patients to contact the study nurse and reduce activity until temperatures normalized. RESULTS: The enhanced therapy group had fewer foot ulcers than the standard therapy and structured foot examination groups (enhanced therapy 8.5 vs. standard therapy 29.3%, P = 0.0046 and enhanced therapy vs. structured foot examination 30.4%, P = 0.0029). Patients in the standard therapy and structured foot examination groups were 4.37 and 4.71 times more likely to develop ulcers than patients in the enhanced therapy group. CONCLUSIONS: Infrared temperature home monitoring, in serving as an "early warning sign," appears to be a simple and useful adjunct in the prevention of diabetic foot ulcerations.

Coronary stents: a materials perspective.

The objective of this review is to describe the suitability of different biomaterials as coronary stents. This review focuses on the following topics: (1) different materials used for stents, (2) surface characteristics that influence stent-biology interactions, (3) the use of polymers in stents, and (4) drug-eluting stents, especially those that are commercially available.

Correlating subjective and objective descriptors of ultra high molecular weight wear particles from total joint prostheses.

A total of 750 images of individual ultra-high molecular weight polyethylene (UHMWPE) particles isolated from periprosthetic failed hip, knee, and shoulder arthroplasties were extracted from archival scanning electron micrographs. Particle size and morphology was subsequently analyzed using computerized image analysis software utilizing five descriptors found in ASTM F1877-98, a standard for quantitative description of wear debris. An online survey application was developed to display particle images, and allowed ten respondents to classify particle morphologies according to commonly used terminology as fibers, flakes, or granules. Particles were categorized based on a simple majority of responses. All descriptors were evaluated using a one-way ANOVA and Tukey-Kramer test for all-pairs comparison among each class of particles. A logistic regression model using half of the particles included in the survey was then used to develop a mathematical scheme to predict whether a given particle should be classified as a fiber, flake, or granule based on its quantitative measurements. The validity of the model was then assessed using the other half of the survey particles and compared with human responses. Comparison of the quantitative measurements of isolated particles showed that the morphologies of each particle type classified by respondents were statistically different from one another (p<0.05). The average agreement between mathematical prediction and human respondents was 83.5% (standard error 0.16%). These data suggest that computerized descriptors can be feasibly correlated with subjective terminology, thus providing a basis for a common vocabulary for particle description which can be translated into quantitative dimensions.

The use of alkanethiol self-assembled monolayers on 316L stainless steel for coronary artery stent nanomedicine applications: an oxidative and in vitro stability study.

The use of self-assembled monolayers (SAMs) on medical devices offers a methodology for the incorporation of nanotechnology into medicine. SAMs are highly ordered nanosized molecular coatings, adding 1 to 10 nm thickness to a surface. This work is part of an overall goal to deliver therapeutic drugs from the surface of metal coronary stents using SAMs. In this study the oxidative and in vitro stability of functional alkylthiol SAMs on 316L stainless steel (SS) has been demonstrated. SAMs of 11-mercaptoundecanoic acid (-COOH SAM) and 11-mercapto-1-undecanol (-OH SAM) were formed on 316L SS. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and contact angle (CA) measurements collectively confirmed the formation of functional alkylthiol SAMs on 316L SS. Well-formed SAMs (CA: 82 deg +/- 9 deg) were achieved within 48 hours of immersion in ethanolic solutions, after which no significant improvement in CA was observed. The ratio of the thiolate peak (163.5 eV) to the oxidized sulfur (sulfonates) peak (166.5 eV) gives us an indication of the percentage SAMs that would bind to the metal and serve as a drug reservoir in vivo; which in turn represents the stability and viability of these SAMs, keeping in mind the cardiovascular application under consideration. Oxidative and in vitro stability studies showed that alkanethiol SAMs oxidized completely within 14 days. The SAMs tend to desorb and leave the metal surface after longer time periods (21 days) in phosphate-buffered saline (PBS) immersion, whereas for oxidative exposure the SAMs continue to remain on the metal surface in the form of sulfonates. Although the chemistry of bonding of alkylthiol with the 316L SS is not well understood, the nanosized alkylthiol SAMs demonstrate sufficient stability to justify further study on these systems for potential in vivo drug delivery in the chosen coronary artery stent applications.

Effect of diabetes mellitus on the material properties of the distal tibia.

This investigation evaluates the effects of diabetes on the mechanical properties of human bone, specifically, the tibia. Seven diabetic and seven nondiabetic human (male) cadaveric distal tibiae were used in this study. The average age of the diabetic cadaveric samples was 51 years (range, 46-61 years), and the average age of the nondiabetic cadaveric samples was 75 years (range, 67-85 years). Three-point bending tests for strength and stiffness were performed on a small sample of each distal tibia. Each specimen was loaded at a constant rate until failure. From the recorded curve of load versus displacement, the ultimate and yield strength of bone and the bending modulus of bone were calculated. The diabetic samples were generally weaker than the older, nondiabetic samples, but no statistically significant differences were found in the elastic modulus (P = .29), yield strength (P = .90), ultimate strength (P = .46), and fracture toughness (P = .78), leading to speculation that diabetes has an effect similar to that of aging on the musculoskeletal system.

Biocompatibility of common polyimides with human endothelial cells for a cardiovascular microsensor.

The cardiovasculature is an emerging niche for polyimide microdevices, yet the biocompatibility of polyimides with human endothelial cells has not been reported in the literature. In this study, we have evaluated an experimental polyimide-based pressure sensor for biological safety to determine its suitability for intravascular operation by using an in vitro model of human endothelium, following ISO 10993-5 protocols for extract tests and direct contact tests. First, SV-HCEC cells were incubated with extracts derived from common microfabrication polyimides utilized in the transducer (PMDA-ODA, BPDA-PPD, and a proprietary thermoplastic adhesive), and then labeled with selective probes to evaluate the effect of the polyimides on mitochondria and cell viability. Flow cytometry analysis showed that incubation of SV-HCECs with polyimide extracts resulted in no significant change in mitochondrial membrane potential (detected by JC-1) or apoptotic (annexin V) and necrotic (propidium iodide) cell death, when compared to incubation with extracts of high-density polyethylene (HDPE) and untreated cells used as negative controls. Second, primary human endothelial cells were incubated in direct contact with the completed sensor and then labeled with selective probes for live-dead analysis (calcein-AM, ethidium homodimer-1). Endothelial cells showed no loss of viability when compared to negative controls. Combined, the studies show no significant change in early markers of stress or more strict markers of viability in endothelial cells treated with the polyimides tested. We conclude that these common microfabrication polyimides and the derived sensor are not cytotoxic to human endothelial cells, the primary cell type that cardiovascular sensors will contact in vivo.

Wear and biomechanical characteristics of a novel shear-reducing insole with implications for high-risk persons with diabetes.

OBJECTIVE: This study was designed to measure pressure and shear reduction of a novel insole design. METHODS: We compared three multilayer viscoelastic insoles to a novel insole design (Glide-Soft, Xilas Medical, Inc., San Antonio, TX). The bottom pad of each insole was fabricated from firm-density Plastazote [Apex Foot Products (now Aetrex), South Hackensack, NJ] with an upper of Plastazote, ethyl vinyl acetate, or PORON (Langer Biomechanics Group, Inc., Deer Park, NY). The GlideSoft design used the same materials with two intervening thin sheets of a low friction material. We measured foot pressures, shear, and material stiffness prospectively as the insoles aged during daily usage in 30 healthy adults. We used the F-Scan (Tekscan, Inc., Boston, MA) to determine in-shoe foot pressures and the Automated Stress-relaxation Creep Indenter System (Xilas Medical) to measure material stiffness. To evaluate shear force, the insole was placed on the slide assembly of a custom-designed shear tester equipped with a reciprocating mechanism and force transducers. RESULTS: The GlideSoft exhibited 57% less peak shear force than the standard insole (P < 0.05) in laboratory testing under simulated conditions. Ethyl vinyl acetate had higher compressive stiffness values than Plastazote and PORON at all test intervals (P < 0.05). There were no statistical differences between any of the insoles for peak in-shoe pressure measurements (P > 0.05). CONCLUSIONS: The GlideSoft design demonstrated a significant reduction in shear while maintaining equivalent pressure reduction compared with standard insole designs with three different material combinations for up to 320,000 steps.

Pullout forces of sutures in muscle lacerations.

The purpose of this study was to determine if complex suture techniques had higher pullout forces from muscle tissue than conventional stitching. Using transected cadaver muscle bellies, we performed repairs with various suture techniques and measured pullout forces. Epimyseal repair with conventional stitches (Kessler, figure eight, horizontal mattress) was inferior to complex stitches (modified Mason-Allen, perimeter). The combined complex stitches (perimeter and Mason-Allen) were strongest. Conventional stitches failed longitudinally through the muscle, whereas complex stitches failed transversely across the muscle. The complex combination of perimeter and Mason-Allen stitches had superior pullout resistance compared to conventional stitches.

Home monitoring of foot skin temperatures to prevent ulceration.

OBJECTIVE: To evaluate the effectiveness of at-home infrared temperature monitoring as a preventative tool in individuals at high risk for diabetes-related lower-extremity ulceration and amputation. RESEARCH DESIGN AND METHODS: Eighty-five patients who fit diabetic foot risk category 2 or 3 (neuropathy and foot deformity or previous history of ulceration or partial foot amputation) were randomized into a standard therapy group (n = 41) or an enhanced therapy group (n = 44). Standard therapy consisted of therapeutic footwear, diabetic foot education, and regular foot evaluation by a podiatrist. Enhanced therapy included the addition of a handheld infrared skin thermometer to measure temperatures on the sole of the foot in the morning and evening. Elevated temperatures (>4 degrees F compared with the opposite foot) were considered to be "at risk" of ulceration due to inflammation at the site of measurement. When foot temperatures were elevated, subjects were instructed to reduce their activity and contact the study nurse. Study subjects were followed for 6 months. RESULTS: The enhanced therapy group had significantly fewer diabetic foot complications (enhanced therapy group 2% vs. standard therapy group 20%, P = 0.01, odds ratio 10.3, 95% CI 1.2-85.3). There were seven ulcers and two Charcot fractures among standard therapy patients and one ulcer in the enhanced therapy group. CONCLUSIONS: These results suggest that at-home patient self-monitoring with daily foot temperatures may be an effective adjunctive tool to prevent foot complications in individuals at high risk for lower-extremity ulceration and amputation.

Age-related changes in the collagen network and toughness of bone.

The hypothesis of this study is that the mechanical integrity of the collagen network in bone deteriorates with age, and such adverse changes correlate with the decreased toughness of aged bone. To test the hypothesis, 30 human cadaveric femurs from donors ranging from 19 to 89 years of age were tested to determine the age-related changes in the mechanical properties of demineralized bone and fresh bone samples. Along with bone porosity, bone density, and weight fractions of the mineral and organic phases, collagen denaturation and concentrations of collagen cross-links (HP, hydroxylysylpyridinoline; LP, lysylpyridinoline; PE, pentosidine) were determined for these bone specimens as a function age. Analysis of variance (ANOVA) showed that age-dependent changes were reflected in the decreased strength, work to fracture, and fracture toughness of bone; in the decreased strength, elastic modulus, and work to fracture of the collagen network; as well as in the increased concentration of pentosidine (a marker of nonenzymatic glycation) and increased bone porosity. Regression analyses of the measured parameters showed that the age-related decrease in work to fracture of bone (especially its postyield portion) correlated significantly with deterioration in the mechanical integrity of the collagen network. The results of this study indicate that the adverse changes in the collagen network occur as people age and such changes may lead to the decreased toughness of bone. Also, the results suggest that nonenzymatic glycation may be an important contributing factor causing changes in collagen and, consequently, leading to the age-related deterioration of bone quality.

Interaction of hydroxyapatite-titanium at elevated temperature in vacuum environment.

In this study, the interaction between hydroxyapatite (HA) and titanium (Ti) at elevated temperature in vacuum environment was investigated. The 80 wt% HA-20 wt% Ti powder mixtures and 90 wt% HA-10 wt% Ti powder mixtures were dry pressed and heat-treated at 1100 degrees C in vacuum environment. HA powders and the commercially pure Ti powders were used as controls. The heat-treated samples were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy, scanning electron microscope (SEM) and energy disperse spectra. XRD and SEM indicated densification of metallic Ti specimens during the in-vacuum heat treatment. Heat treatment of HA specimens in vacuum resulted in the loss of hydroxyl groups as well the formation of a secondary beta-tricalcium phosphate phase. Metallic Ti was not observed in the in-vacuum heat-treated HA-Ti specimens. However, alpha-tricalcium phosphate, tetracalcium phosphate and calcium titanium oxide were observed for the in-vacuum heat-treated HA-Ti specimens. It was concluded that the in-vacuum heat-treatment process completely converted the metal-ceramics composites to ceramic composites.

Efficacy of glow discharge gas plasma treatment as a surface modification process for three-dimensional poly (D,L-lactide) scaffolds.

Gas plasma surface modification of three-dimensional poly (D,L-lactide) scaffolds fabricated by a novel vibrating particle fabrication technique was demonstrated to enhance cell adhesion, proliferation, and differentiation over 10 days in culture using human embryonic palatal mesenchyme cells. Characterization of corresponding two-dimensional treated surfaces revealed decreased contact angle measurements of 54.2 +/- 0.6 degrees for treated surfaces compared to 72.3 +/- 0.7 degrees for control surfaces (p < 0.05). SEM of treated surfaces revealed increased surface roughness combined with marked pitting and erosion. This may contribute to increased cell adhesion. WST-1 cell proliferation assay measurements as an index of cell numbers revealed a statistically significant increase in proliferation activity on treated surfaces on days 1 and 4 compared with controls. There was a fivefold increase in WST-1 activity for both control and treated groups over 10 days. Confocal laser micrographs revealed increased cell numbers on treated specimens throughout all layers of the scaffold, indicating that the glow discharge process enhanced cell proliferation throughout the entire scaffold architecture. Scanning electron micrographs demonstrated increased cell adhesion for treated specimens at the polymer surface most evident after days 1 and 4 of culture. Alkaline phosphatase (ALP)-specific activity peaked by day 7 for control and treated surfaces, indicating cellular differentiation. There was a trend for increased protein production on the treated specimens compared with controls at the initial time points although the differences were not statistically significant. These results demonstrated that gas plasma surface modification enhances osteoblast-like cell function in a three-dimensional scaffold model.

Calcification of primary human osteoblast cultures under flow conditions using polycaprolactone scaffolds for intravascular applications.

Total atherosclerotic occlusion is a leading cause of death. Recent animal models of this disease are devoid of cell-mediated calcification and arteries are often not occluded gradually. This study is part of a project with the objective of developing a new model featuring the above two characteristics, using a tissue-engineering scaffold. The amount and distribution of calcium deposits in primary human osteoblast (HOB) cultures on polycaprolactone (PCL) scaffolds under flow conditions were investigated. HOBs were cultured on PCL scaffolds with TGF-ß1 loadings of 0 (control), 5 and 50 ng. HOB-PCL constructs were cultured in spinner flasks. Under flow conditions, cell numbers present in HOB cultures on PCL scaffolds increased from day 7 to day 14, and most calcification was induced at day 21. TGF-ß1 loadings of 5 and 50 ng did not show a significant difference in ALP activity, cell numbers and amount of calcium deposited in HOB cultures, but calcium staining showed that 50 ng TGF-ß1 had higher calcium deposited on both days 21 and 28 under flow conditions compared with 5 ng of loading. Amount of calcium deposited by HOBs on day 28 showed a decrease from their levels on day 21. PCL degradation may be a factor contributing to this loss. The results indicate that cell-induced calcification can be achieved on PCL scaffolds under flow conditions. In conclusion, TGFß1-HOB loaded PCL can be applied to create a model for total atherosclerotic occlusion with cell-deposited calcium in animal arteries.

Development of a total atherosclerotic occlusion with cell-mediated calcium deposits in a rabbit femoral artery using tissue-engineering scaffolds.

This study sought to establish a chronic total occlusion (CTO) model with cell-mediated calcium deposits in rabbit femoral arteries. CTO is the most severe case in atherosclerosis and contains calcium deposits. Previous animal models of CTO do not mimic the gradual occlusion of arteries or have calcium in physiological form. In the present study we tested the strategy of placing tissue-engineering scaffolds preloaded with cells in arteries to develop a novel CTO model. Primary human osteoblasts (HOBs) were first cultured in vitro on polycaprolactone (PCL) scaffolds with 5 ng TGFß1 loading for 28 days for precalcification. The HOB-PCL construct was then implanted into a rabbit femoral artery for an additional 3, 10 or 28 days. At the time of sacrifice, angiograms and gross histology of arteries were captured to examine the occlusion of arteries. Fluorescent staining of calcium and EDS detection of calcium were used to evaluate the presence and distribution of calcium inside arteries. Rabbit femoral arteries were totally occluded over 28 days. Calcium was presented at CTO sites at 3, 10 and 28 days, with the day 10 specimens showing the maximum calcium. Chronic inflammatory response and recanalization were observed in day 28 CTO sites. A novel CTO model with cell-mediated calcium has been successfully established in a rabbit femoral artery. This model can be used to develop new devices and therapies to treat severe atherosclerotic occlusion.

An in vitro assessment of wear particulate generated from NUBAC: a PEEK-on-PEEK articulating nucleus replacement device: methodology and results from a series of wear tests using different motion profiles, test frequencies, and environmental conditions.

STUDY DESIGN: In vitro biotribological wear particulate investigation. OBJECTIVE: To characterize poly-ether-ether-ketone (PEEK)-OPTIMA wear particulate generated from a series of wear tests used to evaluate the wear resistance and long-term biodurability of NUBAC, a PEEK-on-PEEK articulating nucleus replacement device, and compare with wear particulate associated with hip and knee total joint arthroplasties. SUMMARY OF BACKGROUND DATA: The use of PEEK in spinal arthroplasty represents a unique application of this material. Clinically, osteolysis, osteolytic changes, and adverse reactions to metal ions have been documented in spinal arthroplasty. Therefore, it is critically important to analyze the PEEK wear particulate to evaluate its resultant biologic reactivity. Historically, scanning electron microscopy (SEM) has been used for wear debris characterization. Light scattering, specifically laser diffraction, has also been successfully used. The combined use of both techniques may provide a more comprehensive analysis than either method alone. METHODS: Proteinacious serum containing PEEK wear debris generated from four groups of devices from separate wear tests underwent enzymatic and acid digestion. The particulate was analyzed using laser diffraction in duplicate, followed by SEM analysis. RESULTS: Laser diffraction analysis demonstrated a relatively large mean particle diameter on the basis of particle volume (16.5-40.0 µm) as compared with particle number (0.9-2.2 µm). For all groups, more than 50% of debris was larger than 5.0 µm. SEM analysis revealed a mean particle size consistent with the number-based laser diffraction results. The morphology of the wear particulate appeared to be similar for all the groups analyzed. CONCLUSION: The analysis of the particles generated from an articulating PEEK-on-PEEK nucleus replacement device shows debris within size ranges typical of other total joint arthroplasty implants, with relatively round morphology, along with the results suggesting a reduced particle load. These attributes tend to diminish the potential of these PEEK particles to elicit an inflammatory response.

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.

Migration of co-cultured endothelial cells and osteoblasts in composite hydroxyapatite/polylactic acid scaffolds.

Regeneration of bone in large segmental bone defects requires regeneration of both cortical bone and trabecular bone. A scaffold design consisting of a hydroxyapatite (HA) ring surrounding a polylactic acid (PLA) core simulates the structure of bone and provides an environment for indirect and direct co-culture conditions. In this experiment, human umbilical vein endothelial cells (EC) and normal human primary osteoblasts (OB) were co-cultured to evaluate cell migration and interactions within this biphasic composite scaffold. Both cell types were able to migrate between the different material phases of the scaffold. It was also observed that OB migration increased when they were co-cultured with ECs, whereas EC migration decreased in co-culture. The results show that co-culture of ECs and OBs in this composite biphasic scaffold allows for migration of cells throughout the scaffold and that pre-seeding a scaffold with ECs can increase OB infiltration into desired areas of the scaffold.

Stability of antibacterial self-assembled monolayers on hydroxyapatite.

Open fractures are common in battlefields, motor vehicle accidents, gunshot wounds, sports injuries, and high-energy falls. Such fractures are treated using hydroxyapatite (HA)-based bone graft substitutes. However, open fracture wounds are highly susceptible to bacterial infections. Hence, this study was focused on incorporating antibacterial properties to HA using silver (Ag) carrying self-assembled monolayers (SAMs). Also, the stability of Ag carrying SAMs on HA was investigated under sterilization and physiological conditions. Initially, the -COOH terminated phosphonic acid SAMs of two different chain lengths (11 carbon atoms - shorter chain and 16 carbon atoms - longer chain) were deposited on HA. Antibacterial SAMs (ASAMs) were prepared by chemically attaching Ag to shorter and longer chain SAMs coated HA. X-ray photoelectron spectroscopy, atomic force microscopy, and contact angle goniometry collectively confirmed the attachment of Ag onto SAMs coated HA. The bacterial adhesion study showed that the adherence of Staphylococcus aureus was significantly reduced on ASAMs coated HA when compared to control-HA. The stability studies showed that gas plasma, dry heat and autoclave degraded most of the ASAMs on HA. UV irradiation did not damage the shorter chain ASAMs as vigorously as other treatments, while it degraded the longer chain ASAMs completely. Ethylene oxide treatment did not degrade the longer chain ASAMs unlike all other treatments but it severely damaged the shorter chain ASAMs. Both shorter and longer chain ASAMs significantly desorbed from the HA surfaces under physiological conditions although longer chain ASAMs exhibited better stability than shorter chain ASAMs. This study demonstrated the potential for using ASAMs to provide antibacterial properties to HA and the need for developing techniques to improve stability of SAMs under sterilization and physiological conditions.

Interaction of endothelial cells with self-assembled monolayers for potential use in drug-eluting coronary stents.

Drug-eluting stents (DES) are implanted in patients to treat in-stent restenosis. Commercially available DES use polymers for coating and releasing drugs. Several studies have showed that polymer coatings cause adverse reactions. Delayed endothelialization of polymer-coated DES leads to late stent thrombosis. Recently, the potential for using self-assembled monolayers (self-assembled monolayers (SAMs)-organic constructs composed of (a) chemical groups which attach to metal surfaces, (b) long hydrocarbon chains, and (c) terminal functional groups) as an alternate drug delivery system for coronary stents has been demonstrated. In this study, the interaction of human aortic endothelial cells (HAECs) with SAMs and therapeutic SAMs (therapeutic self-assembled monolayers (TSAMs)-SAMs derivatized with the drug, flufenamic acid) was investigated. HAECs were cultured on plain glass, control, SAMs-, and TSAMs-coated titanium (Ti) and gold (Au) specimens. The viability and proliferation of HAECs were investigated using MTT colorimetric assay. The adhesion of HAECs on SAMs and TSAMs was equivalent to that of control metal surfaces and superior to that of plain glass surfaces. The cells continued to proliferate on both SAMs and TSAMs even though the rate of proliferation was slower than plain glass or control-Ti. The spreading of HAECs on TSAMs with typical polygonal shape indicated that these surfaces are conducive to endothelialization. The expression of surface adhesion protein, platelet endothelial cell adhesion molecule-1, on TSAMs indicated that the endothelial cells preserved their phenotype on these surfaces. Thus, this study demonstrated that SAMs and TSAMs do not elicit an adverse response from endothelial cells in in vitro conditions.