Progress in bioactive surface coatings on biodegradable Mg alloys: A critical review towards clinical translation.

Mg and its alloys evince strong candidature for biodegradable bone implants, cardiovascular stents, and wound closing devices. However, their rapid degradation rate causes premature implant failure, constraining clinical applications. Bio-functional surface coatings have emerged as the most competent strategy to fulfill the diverse clinical requirements, besides yielding effective corrosion resistance. This article reviews the progress of biodegradable and advanced surface coatings on Mg alloys investigated in recent years, aiming to build up a comprehensive knowledge framework of coating techniques, processing parameters, performance measures in terms of corrosion resistance, adhesion strength, and biocompatibility. Recently developed conversion and deposition type surface coatings are thoroughly discussed by reporting their essential therapeutic responses like osteogenesis, angiogenesis, cytocompatibility, hemocompatibility, anti-bacterial, and controlled drug release towards in-vitro and in-vivo study models. The challenges associated with metallic, ceramic and polymeric coatings along with merits and demerits of various coatings have been illustrated. The use of multilayered hybrid coating comprising a unique combination of organic and inorganic components has been emphasized with future perspectives to obtain diverse bio-functionalities in a facile single coating system for orthopedic implant applications.

Preliminary Validation of a Dynamic Electrochemical Biodegradation Test Bench in Pseudo-Physiological Conditions.

There is a growing interest in the development of next generation stent materials. In vitro tests that accurately predict in vivo conditions, are needed for a full evaluation of a material's corrosion in vivo. In this manuscript a novel approach for the design of a dynamic electrochemical test bench is evaluated in hopes to later characterize and model biodegradable metallic stent materials. This dynamic test bench design allows for real-time corrosion testing with easy variation of temperature, shear stress, and simulated body fluids (SBF), with minimal complications of test sample fabrication. Preliminary tests have shown Tafel generation stable. Further testing of the stability of the test bench were conducted with the incorporation SBF, shear stress, and temperature. Shear stress was applied through variation in fluid velocities at 0 m/s, 0.127 m/s, 0.245 m/s, 0.372 m/s, 0.489 m/s at 37°C. Incorporation of the different SBFs showed no significant difference in corrosion readings; however, variances were observed higher in DMEM and PBS, than in Hanks, respectively. This dynamic test bench showed to be relatively stable under temperature and SBF modification; however, further optimization is needed to decrease variances seen throughout fluid velocity analysis.

Bio-functional nano-coatings on metallic biomaterials.

Metals and their alloys have been widely used in all aspects of science, engineering and medicine. Metals in biomedical devices are used due to their inertness and structural functions. They are generally preferred over polymers or ceramics and are especially desirable in applications where the implants are subjected to static, dynamic or cyclic loads that require a combination of strength and ductility. In biomedicine, the choice of a specific biomaterial is governed by many factors that include biocompatibility, corrosion resistance, controlled degradability, modulus of elasticity, fatigue strength and many other application specific criterions. Nanotechnology is driving newer demands and requirements for better performance of existing materials and presents an opportunity for surface modification of metals in response to demands on the surface of metals for their biomedical applications. Self-assembled monolayers (SAMs) are nanosized coatings that present a flexible method of carrying out surface modification of biomaterials to tailor its surface properties for specific end applications. These nanocoatings can serve primary functions such as surface coverage, etch protection and anti-corrosion along with a host of other secondary chemical functions such as drug delivery and biocompatibility. We present a brief introduction to surface modification of biomaterials and their alloys followed by a detailed description of organic nanocoatings based on self-assembled monolayers and their biomedical applications including patterning techniques and biological applications of patterned SAMs.

Percutaneous Transcatheter Closure of Ruptured Sinus of Valsalva Aneurysm: Immediate Result and Long-Term Follow-Up.

There is scarcity of data on closure and long-term follow-up of percutaneous treatment of ruptured sinus of Valsalva aneurysm (RSOVA). In this article, we present our experience in percutaneous closure of this defect. Between December 2009 and July 2014, 11 cases of RSOVA were referred to our hospital. Eight of the 11 cases (72.7%) were considered for percutaneous closure. Seven of the eight (87.5%) patients underwent successful percutaneous closure. There were four females and three males in the age group of 16 to 48 years (mean 24.7 ± 6.1 years). Associated defects were bicuspid aortic valve in one patient, mild preexisting aortic regurgitation in two patients, and healed infective endocarditis in one patient. Echocardiography revealed RSOVA from right coronary sinus (RCS) to right atrium (RA) in one patient (14.3%), RCS to right ventricular outflow in three patients (42.8%), and noncoronary sinus ruptured into RA in three patients (42.8%). All patients were symptomatic in New York Heart Association (NYHA) class II to IV. The defect size ranged from 7 to 10 mm (mean 8.4 ± 1.3 mm). The defects were closed from the venous side with device selection 2 to 4 mm higher than the defect size under fluoroscopy and transesophageal echocardiography guidance. Technical success was 87.5%. The mean device size was 12.0 ± 1.6 mm/10.0 ± 1.6 mm. Six out of seven patients (85.7%) had complete disappearance of shunt before discharge. During 1 to 55 months follow-up, all patients were in NYHA class I. There was no residual shunt, progression of AR or new AR, infective endocarditis or device embolization. Percutaneous closure of RSOVA appears to be a safe alternative to surgical therapy, with high technical success and excellent long-term outcome.

Isolated single coronary artery presenting as acute coronary syndrome: case report and review.

Congenital single coronary artery is commonly associated with complex congenital heart diseases and manifests in infancy or childhood. But isolated single coronary artery is a rare congenital anomaly which can present as acute coronary syndrome in adults. The aim of the work is to discuss on isolated single coronary artery in two adults presenting as acute coronary syndrome. The first case underwent coronary angiography (CAG) through right radial route, but switched over to femoral for confirmation of diagnosis and due to radial spasm. An aortic root angiogram was done to rule out presence of any other coronary ostia. It revealed a single coronary artery originating from right sinus of valsalva. After giving rise to posterior descending artery branch at crux, it continued in the atrioventricular groove to the anterior basal surface of the heart and traversed as anterior descending artery. There was no atheromatous occlusive stenosis. This is R-I type single coronary artery as per Lipton classification. In the second case, angiography was completed through right radial route. It revealed a single coronary artery arising from right aortic sinus. Anterior descending and circumflex branch were originating from proximal common trunk of the single coronary artery and supplying the left side of the heart. The right coronary artery has diffuse atheromatous disease without significant stenosis in any major branch. This is R-III C type as per Lipton classification. A coronary anomaly of both origin and course is very rare. It may be encountered in adults evaluated for atherosclerotic coronary heart disease. Knowledge and understanding of anatomical types of this congenital anomaly will reduce time, anxiety, complications during CAG and cardiac surgery.

In vitro stability study of organophosphonic self assembled monolayers (SAMs) on cobalt chromium (Co-Cr) alloy.

Surface modification of cobalt chromium (Co-Cr) alloy is being investigated as a possible solution to the biomedical challenges arising from its usage. Self assembled monolayers (SAMs) of organophosphonic octadecylphosphonic acid (ODPA) were formed on the oxide surface of Co-Cr alloy by chemisorption using the solution deposition technique. High quality and well-ordered SAMs were formed which were characterized using Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), contact angle measurements and ellipsometry. The resulting monolayers were then exposed to in vitro conditions using phosphate buffered saline (PBS) solution. The samples were analyzed for a period of 1, 3, 7 and 14 days. The resulting samples were characterized using XPS, AFM and Contact angle measurements. XPS atomic concentrations and detailed high energy elemental scans gave an insight into the trends of elemental concentrations over the duration of the study. SAMs were found to be strongly bound to the oxide surface after PBS exposure. AFM gave the topographic details of SAMs presence by island formation before and after SAM formation and also over the duration of the PBS exposure. Contact Angle Measurements confirmed the hydrophobicity of the surface after SAM formation and indicated a slight disorder of the SAM alkyl chain upon exposure to PBS. Thus, ODPA SAMs were successfully coated on Cobalt Chromium (Co-Cr) alloy surface and were found to be stable and strongly bound after PBS exposure.

Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines.

Biodegradable nanoparticles (NPs) are gaining increased attention for their ability to serve as a viable carrier for site specific delivery of vaccines, genes, drugs and other biomolecules in the body. They offer enhanced biocompatibility, superior drug/vaccine encapsulation, and convenient release profiles for a number of drugs, vaccines and biomolecules to be used in a variety of applications in the field of medicine. In this manuscript, the methods of preparation of biodegradable NPs, different factors affecting optimal drug encapsulation, factors affecting drug release rates, various surface modifications of nanoparticles to enhance in-vivo circulation, distribution and multimodal functionalities along with the specific applications such as tumor targeting, oral delivery, and delivery of these particles to the central nervous system have been reviewed.

Stability of Phosphonic Self Assembled Monolayers (SAMs) on Cobalt Chromium (Co-Cr) Alloy under Oxidative conditions.

Cobalt Chromium (Co-Cr) alloys has been widely used in the biomedical arena for cardiovascular, orthopedic and dental applications. Surface modification of the alloy allows us to tailor the interfacial properties to address critical challenges of Co-Cr alloy in medical applications. Self assembled monolayers (SAMs) of Octadecylphosphonic acid (ODPA) have been used to form thin films on the oxide layer of the Co-Cr alloy surface by solution deposition technique. The SAMs formed were investigated for their stability to oxidative conditions of ambient laboratory environment over periods of 1, 3, 7 and 14 days. The samples were then characterized for their stability using X-ray Photoelectron Spectroscopy (XPS), Atomic Force Microscopy (AFM) and Contact Angle Measurements. Detailed high energy XPS elemental scans confirmed the presence of the phosphonic monolayer after oxidative exposure which suggested that the SAMs were firmly attached to the oxide layer of Co-Cr alloy. AFM images gave topographical data of the surface and showed islands of SAMs on Co-Cr alloy surface, before and after SAM formation and also over the duration of the oxidative exposure. Contact angle measurements confirmed the hydrophobicity of the surface over 14 days. Thus the SAMs were found to be stable for the duration of the study. These SAMs could be subsequently tailored by modifying the terminal functional groups and could be used for various potential biomedical applications such as drug delivery, biocompatibility and tissue integration.

Nanosized controlled surface pretreatment of biometallic alloy 316L stainless steel.

Stainless steel (AISI 316L) is a medical grade stainless steel alloy used extensively in medical devices and in the biomedical field. 316L stainless steel was successfully electropolished via an ecologically friendly and biocompatible ionic liquid (IL) medium based on Vitamin B4 (NB4) and resulting in nanosized surface roughness and topography. Voltammetry and chronoamperometry tests determined optimum polishing conditions for the stainless steel alloy while atomic force microscopy (AFM) and scanning electron microscopy (SEM) provided surface morphology comparisons to benchmark success of each electropolishing condition. Energy dispersive X-ray analysis (EDX) combined with SEM revealed significantly smoother surfaces for each alloy surface while indicating that the constituent metals comprising each alloy effectively electropolished at uniform rates.

Formation of nanosized phosphonic acid self assembled monolayers on cobalt-chromium alloy for potential biomedical applications.

Formation of nanosized self assembled monolayers (SAMs) of carboxyl terminated 16-Phosphonohexadecanoic acid (16-PA) and methyl terminated Octadecylphosphonic acid (ODPA) on Cobalt-Chromium (Co-Cr) alloy have been successfully demonstrated. Nanosized monolayers were formed by adsorption of these phosphonic acid SAMs on bare Co-Cr alloy by solution deposition technique. The formation of the nanosized monolayers was confirmed by using characterization techniques like Fourier Transform Infrared Spectroscopy (FTIR) with Attenuated Total Reflectance (ATR) attachment, Atomic Force Microscopy (AFM), X-ray Photoelectron Spectroscopy (XPS), Ellipsometry and Contact Angle measurements. FTIR confirmed the SAM formation due to the presence of characteristic stretching vibration of SAM functional groups. FTIR studies suggest the binding of the phosphonic SAMs to be a combination of mono and bidentate binding. XPS showed presence of phosphorous peak and an increase in carbon peak intensity after SAM deposition, while it consequently showed decrease in peak intensity of the metal alloy (Co and Cr) peaks. AFM images gave good understanding of the topography, surface roughness and uniformity of SAM formation. Ellipsometric studies indicate nanosized thickness of the SAMs formed, while contact angle measurements showed changes in surface hydrophilicity/hydrophobicity after SAM formation. By tailoring the terminal functional group of these SAMs on Co-Cr alloy these nanosized monolayers could be potentially used for various biomedical applications such as localized drug delivery, biocompatibility, tissue integration etc.

Drug delivery from therapeutic self-assembled monolayers (T-SAMs) on 316L stainless steel.

Delivery of therapeutic agents from self-assembled monolayers (SAMs) on 316L stainless steel (SS) has been demonstrated as a viable method to deliver drugs for localized coronary artery stent application. SAMs are highly-ordered, nano-sized molecular coatings, adding 1-10 nm thickness to a surface. Hydroxyl terminated alkanethiol SAMs of 11-mercapto-1-undecanol (-OH SAM) were formed on 316L SS with 48 hr immersion in ethanolic solutions. Attachment of ibuprofen (a model drug) to the functional SAMs was carried out in toluene for 5 hrs at 60 degrees C using Novozume-435 as a biocatalyst. SAM formation and subsequent attachment of ibuprofen was characterized collectively using X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and contact angle (CA) measure-ments. The quantitative in vitro release of ibuprofen into a "physiological" buffer solution was characterized using reverse phase HPLC. Drug release kinetics showed that 14.1 microg of ibuprofen eluted over a period of 35 days with 2.7microg being eluted in the first day and the remaining being eluted over a period of 35 days. The drug release kinetics showed an increase in ibuprofen elution that occurred during first 14 days (2.7microg in 1 day to 9.5 microg in 14 days), following which there was a decrease in the rate of elution. Thus, functional SAMs on 316L SS could be used as tethers for drug attachment and could serve as a drug delivery mechanism from stainless steel implants such as coronary artery stents.

Surface modification of functional self-assembled monolayers on 316L stainless steel via lipase catalysis.

Lipase catalyzed esterification of therapeutic drugs to functional self-assembled monolayers (SAMs) on 316L stainless steel (SS) after assembly has been demonstrated. SAMs of 16-mercaptohexadecanoic acid (-COOH SAM) and 11-mercapto-1-undecanol (-OH SAM) were formed on 316L SS, and lipase catalysis was used to attach therapeutic drugs, perphenazine and ibuprofen, respectively, on these SAMs. The reaction was carried out in toluene at 60 degrees C for 5 h using Novozyme-435 as the biocatalyst. The FTIR spectra after surface modification of -OH SAMs showed the presence of the C=O stretching bands at 1745 cm(-1), which was absent in the FTIR spectra of -OH SAMs. Similarly, the FTIR spectra after the reaction of the -COOH SAM with perphenazine showed two peaks in the carbonyl region, a peak at 1764 cm(-1), which is the representative peak for the C=O stretching for esters. The second peak at 1681 cm(-1) is assigned to the C=O stretching of the remaining unreacted terminal COOH. XPS spectra after lipase catalysis with ibuprofen showed a photoelectron peak evolving at 288.5 eV which arises from the carbon (C=O) of the carboxylic acid of the drug (ibuprofen). Similarly for -COOH SAMs, after esterifiation we see a small, photoelectron peak evolving at 286.5 eV which corresponds to the C in the methylene groups adjacent to the oxygen (C-O), which should evolve only after the esterification of perphenazine with the -COOH SAM. Thus, lipase catalysis provides an alternate synthetic methodology for surface modification of functional SAMs after assembly.

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.

Mild, solvent-free omega-hydroxy acid polycondensations catalyzed by candida antarctica lipase B.

Immobilized Candida antarctica Lipase B (Novozyme-435) was studied for bulk polyesterifications of linear aliphatic hydroxyacids of variable chain length. The products formed were not fractionated by precipitation. The relative reactivity of the hydroxyacids was l6-hydroxyhexadecanoic acid approximately 12-hydroxydodecanoic acid approximately 10-hydroxydecanoic acid (DPavg congruent with 120, Mw/Mn 6-hydroxyhexanoic acid (DPavg congruent with 80, Mw/Mn < or = 1.5, 48 h, 90 degrees C). Remarkable improvements in molecular-weight buildup resulted from leaving water in the reaction. By 4 h, without application of vacuum, the DPavg for 12- and 16-carbon hydroxyacids was about 90. In contrast, with identical substrates and water removal, the DPavg at 4 h was about 23. Large differences in the molecular-weight build up of 12-hydroxydodecanoic acid were observed for catalyst concentrations (%-by-wt relative to monomer) of 0.1, 0.5, 1, and 10. Nevertheless, by 24 h, with 1% catalyst containing 0.1% lipase, poly(12-hydroxydodecanoic acid) with Mn 17 600 was formed. For 12-hydroxydodecanoic acid polymerization at 90 degrees C, the catalyst activity decreased by 7, 18, and 25% at reaction times of 4, 24, and 48 h, respectively. Furthermore, the retention of catalyst activity was invariable as a function of the substrates used.

Lipase-catalyzed polycondensations: effect of substrates and solvent on chain formation, dispersity, and end-group structure.

The effects of substrates and solvent on polymer formation, number-average molecular weight (M(n)), polydispersity, and end-group structure for lipase-catalyzed polycondensations were investigated. Diphenyl ether was found to be the preferred solvent for the polyesterification of adipic acid and 1,8-octanediol giving a M(n) of 28 500 (48 h, 70 degrees C). The effect of varying the alkylene chain length of diols and diacids on the molecular weight distribution and the polymer end-group structure was assessed. A series of diacids (succinic, glutaric, adipic, and sebacic acid) and diols (1,4-butanediol, 1,6-hexanediol, and 1,8-octanediol) were polymerized in solution and in bulk. It was found that reactions involving monomers having longer alkylene chain lengths of diacids (sebacic and adipic acid) and diols (1,8-octanediol and 1,6-hexanediol) give a higher reactivity than reactions of shorter chain-length diacids (succinic and glutaric acid) and 1,4-butanediol. The bulk lipase-catalyzed condensation reactions were feasible, but the use of diphenyl ether gave higher M(n) values (42,400 g/mol in 3 days at 70 degrees C). The polydispersity varied little over the conditions studied giving values