Bioengineering of Improved Biomaterials Coatings for Extracorporeal Circulation Requires Extended Observation of Blood-Biomaterial Interaction under Flow

Extended use of cardiopulmonary bypass (CPB) systems is often hampered by thrombus formation and infection. Part of these problems relates to imperfect hemocompatibility of the CPB circuitry. The engineering of biomaterial surfaces with genuine long-term hemocompatibility is essentially virgin territory in biomaterials science. For example, most experiments with the well-known Chandler loop model, for evaluation of blood-biomaterial interactions under flow, have been described for a maximum duration of 2 hours only. This study reports a systematic evaluation of two commercial CPB tubings, each with a hemocompatible coating, and one uncoated control. The experiments comprised (i) testing over 5 hours under flow, with human whole blood from 4 different donors; (ii) measurement of essential blood parameters of hemocompatibility; (iii) analysis of the luminal surfaces by scanning electron microscopy and thrombin generation time measurements. The dataset indicated differences in hemocompatibility of the tubings. Furthermore, it appeared that discrimination between biomaterial coatings can be made only after several hours of blood-biomaterial contact. Platelet counting, myeloperoxidase quantification, and scanning electron microscopy proved to be the most useful methods. These findings are believed to be relevant with respect to the bioengineering of extracorporeal devices that should function in contact with blood for extended time

VEGF-E enhances endothelialization and inhibits thrombus formation on polymeric surfaces

Thrombotic complications of long-terra blood-contacting devices can be avoided by formation of an endothelial cell layer on the blood-contacting surface. The endothelial cells form a bioactive boundary between the synthetic surface and blood, regulating ha haemostasis and inflammation. Biofunctionalization of synthetic blood-collecting surfaces is necessary to accommodate growth of endothelial cells. Vascular endothelial growth factor E (VEGF-F) or collagen I may stimulate endothelialization of a polymeric surface coating of a prototype small diameter vascular prosthesis. VEGF-E was produced hi Escherichia coli and could be easily purified in large quantities. Recombinant VEGF-E or purified collagen I was allowed to adsorb onto the polymeric surfaces and enhanced formation of an endothelial cell layer. Adsorption of VEGF-E was increased by the inclusion Of the anti-coagulant drug heparin in the polymeric coating. Collagen I adsorption induced rapid thrombin generation and increased platelet adhesion of surfaces with or without heparin. VEGF-E a( inhibited thrombus formation, and did not interfere with the anti-thrombogemic effect of heparin). Additionally, VEGF-E did not affect platelet adhesion. Adsorption of VEGF-E, especially on heparin containing surfaces, provides an economical strategy to improve endothelialization of cardiovascular implants without disturbing blood-compatibility

Polymeric Microspheres Designed to Carry Crystalline Drugs at Their Surface or Inside Cavities and Dimples

Injectable polymer microparticles with the ability to carry and release pharmacologically active agents are attracting more and more interest. This study is focused on the chemical synthesis, characterization, and preliminary exploration of the utility of a new type of injectable drug-releasing polymer microparticle. The particles feature a new combination of structural and physico-chemical properties: (i) their geometry deviates from the spherical in the sense that the particles have a cavity; (ii) the particles are porous and can therefore be loaded with crystalline drug formulations; drug crystals can reside at both the particle’s surfaces and inside cavities; (iii) the particles are relatively dense since the polymer network contains covalently bound iodine (approximately 10% by mass); this renders the drug-loaded particles traceable (localizable) by X-ray fluoroscopy. This study presents several examples. First, the particles were loaded with crystalline voriconazole, which is a potent antifungal drug used in ophthalmology to treat fungal keratitis (infection/inflammation of the cornea caused by penetrating fungus). Drug loading as high as 10% by mass (=mass of immobilized drug/(mass of the microparticle + mass of immobilized drug) × 100%) could be achieved. Slow local release of voriconazole from these particles was observed in vitro. These findings hold promise regarding new approaches to treat fungal keratitis. Moreover, this study can help to expand the scope of the transarterial chemoembolization (TACE) technique since it enables the use of higher drug loadings (thus enabling higher local drug concentration or extended therapy duration), as well as application of hydrophobic drugs that cannot be used in combination with existing TACE embolic particles

Recent advances in surface functionalization techniques on polymethacrylate materials for optical biosensor applications

Biosensor chips for immune-based assay systems have been investigated for their application in early diagnostics. The development of such systems strongly depends on the effective protein immobilization on polymer substrates. In order to achieve this complex heterogeneous interaction the polymer surface must be functionalized with chemical groups that are reactive towards proteins in a way that surface functional groups (such as carboxyl, -COOH; amine, -NH2; and hydroxyl, -OH) chemically or physically anchor the proteins to the polymer platform. Since the proteins are very sensitive towards their environment and can easily lose their activity when brought in close proximity to the solid surface, effective surface functionalization and high level of control over surface chemistry present the most important steps in the fabrication of biosensors. This paper reviews recent developments in surface functionalization and preparation of polymethacrylates for protein immobilization. Due to their versatility and cost effectiveness, this particular group of plastic polymers is widely used both in research and in industry

Influence of powder-to-liquid monomer ratio on properties of an injectable iodine-containing acrylic bone cement for vertebroplasty and balloon kyphoplasty

The interventional radiological techniques of vertebroplasty (VP) and balloon kyphoplasty (BKP) are widely used in cases where the pain secondary to compression fractures of vertebral bodies is severe, persistent, and refractory to conservative treatments. In the majority of VP and BKP cases, an injectable poly(methyl methacrylate) (PMMA) bone cement and different values of powder-to-liquid monomer ratio (PLMR) are used. A systematic study of the influence of PLMR on relevant cement properties is lacking. This was the subject of the present study, with the injectable PMMA bone cement used being an experimental one whose radiopacity is provided by an iodine-containing compound in the powder. The PLMRs used-1.54, 2.22, and 3.08 g mL-1-are within the range used in clinical reports on VP and BKP. One property of the curing cement, namely, the polymerization rate at 37°C (k′), was estimated using nonisothermal differential scanning calorimetry results. The fatigue lives (Nf) of cured cement specimens were obtained under axial loading corresponding to axial stresses (S) of ±20.0, 15.0, 12.5, and 10.0 MPa, at a frequency of 2 Hz. The fatigue limit of the cement was estimated from the fit of the S - Nf results to the Olgive equation. With increase in PLMR, k′ increased significantly, but the influence of PLMR on the fatigue limit and on another property also estimated from the S - ln Nf results is not significant. © 2009 Wiley Periodicals, Inc