Lyuba I. Mikhalovska

In vitro host response assessment of biomaterials for cardiovascular stent manufacture

The deployment of a vascular stent during angioplasty has greatly reduced the risks of restenosis. However, the presence of the device still induces a host response as well as a mechanical action on the blood vessel wall and an alteration of the haemodynamics. Platelet and inflammatory cells can adhere on the stent surface and be activated to produce biochemical signals able to stimulate an excessive proliferation of the smooth muscle cells with the consequent obstruction of the vessel lumen. For these reasons, the host response to two of the materials used in stent manufacture, stainless steel and diamond-like carbon, was investigated in vitro. The data showed that stainless steel induced a higher level of host response both in terms of platelet aggregation and macrophage activation. However, the spreading of inflammatory cells was more accentuated on diamond-like carbon. The inflammatory cells produced levels of platelet-derived growth factor, a key signal in smooth muscle cell proliferation, similar to stainless steel thus suggesting that carbon coatings may not be able to prevent restenosis.

Fibrinogen adsorption and platelet adhesion to metal and carbon coatings

In order to study the haemocompatibility of metal and carbon coatings, fibrinogen adsorption and platelet adhesion to various coatings have been investigated. Two metallic coatings--titanium and zirconium, and two carbon coatings - isotropic diamond-like and isotropic graphite-like coatings, were prepared by plasma vapour deposition onto stainless steel substrate. It has been shown that the adsorption of fibrinogen to metal and carbon coatings and its post-adsorptive transition are dependent on both the material properties and the fibrinogen environment. The adsorption of fibrinogen from human plasma on titanium and zirconium coatings is similar to that on uncoated stainless steel surface. Both carbon coatings adsorb much greater amount of fibrinogen from plasma, and fibrinogen retention by carbon surfaces is also greater than by metal surfaces. Increased numbers of adhered platelets have been found on both carbon coatings in comparison to the metal materials, although this does not correlate with the amount of adsorbed fibrinogen.

Nano carriers for drug transport across the blood–brain barrier

Abstract Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood–brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug–carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully discussed.

Characterisation and performance of hydrogel tissue scaffolds

Porosity over a broad range (typically 0.001–300 μm in diameter) of tissue scaffolds provides appropriate conditions for diffusion and adsorption of small molecules and macromolecules, migration of cells through the scaffold, and adequate cell proliferative capacity. Characterisation of pores over this large range poses a problem especially when analysing soft polymer hydrogels, as no one methodology can adequately cover the entire range. This work describes a combined technique used for evaluation of the porous structure of a collagen hydrogel (dermal substitute Integra®) on the basis of NMR-cryoporometry (sensitive to nanopores) and confocal laser scanning microscopy (CLSM) imaging (sensitive to macropores). Thermodesorption of water, diffusion of proteins through a collagen membrane, migration and growth of normal primary human skin fibroblasts, and the interaction kinetics of 3T3 mouse fibroblast cells (using a quartz crystal microbalance) with collagen were analysed with respect to the porous structure of the material. The contribution to the total porosity of pores with a diameter of less than 100 nm is low, at approximately 3–5%, a figure estimated using the methods described above. However, these pores are the main contributor to the specific surface area (S ≈ 120 m2 g−1) as larger diameter macropores, with diameters of 20–200 μm, have a much lower surface area at S ≈ 0.4 m2 g−1 relative to their large pore volume V = 14.4 cm3 g−1.

Inorganic coatings for cardiovascular stents: In vitro and in vivo studies

The in-vitro and in-vivo biocompatibility of two oxides (TiO and ZrO) and diamond-like carbon (D) coated stents has been assessed and compared with uncoated stainless steel (St) stents. In vitro studies demonstrated that both fibrinogen adsorption and platelet adhesion were significantly higher on D coating compared to those on oxide coatings and uncoated stainless steel. In addition TiO and ZrO coatings showed evidence of a minor inflammatory response and more complete endothelialization of the aorta than that seen around D coated and uncoated St stents. The resulting neointimal growth in the aorta with TiO, ZrO, and D coated and uncoated St stents, measured 8 weeks after stenting (the ratio of the neointima in the stented artery to the non-stented artery) was 1.03 + 0.28, 0.85 + 0.36, 1.78 + 1.26, and 1.15 + 0.56, accordingly. From the data obtained it could be concluded that the increased neointima measured around D-coated stents, may be due to both, the inferior haemocompatibility of the diamond-like carbon coating and mechanical instability of D coating observed in an in vivo environment.

A comparative study of air-dry and water swollen flax and cotton fibres

Thermal stability and structural characteristics of air-dry and swollen crude flax, bleached flax and cotton fibres and the behaviour of bound water were analysed using thermogravimetry, microscopy, differential scanning calorimetry, low-temperature 1H NMR spectroscopy and cryoporometry methods. Both air-dry and swollen fibres contain strongly (SBW) and weakly (WBW) bound water which differ in their behaviour at temperatures below 273 K. All samples have a higher content of SBW than WBW because of the structural features of natural fibres. The air-dry fibres studied have low porosity and similar inner mesoporous structure. The air-dry fibre samples of both cotton and bleached flax contain mainly SBW located in nanopores with radius R 10 nm. According to cryoporometry, swelling substantially increases the pore volume (by a factor of 20–30) and specific surface area Smeso (two–three times) of fibres in the mesoporous region. The largest changes were observed in cotton fibres, owing to their chemical structure and textural characteristics affected by swelling. In the nanopore range, swelling reduced the specific surface area of nanopores (Snano) in cotton fibres and increased Snano in flax fibres, so that for air-dry samples of all fibres Snano > Smeso but for swollen samples Snano < Smeso.

Cottonised flax fibres vs. cotton fibres: structural, textural and adsorption characteristics

Structural (crystallinity), textural (pore volume, Vp, specific surface area, SBET, pore size distribution, PSD) and adsorption characteristics of bleached flax fibres and cotton fibres have been determined using equilibrium adsorption of nitrogen, water, chlorhexidine diacetate (CHX) and methylene blue (MB), adsorption–desorption kinetics of MB and CHX, X-ray diffraction, infrared spectroscopy, thermogravimetry, differential scanning calorimetry (DSC) and DSC cryoporometry. Air-dry, degassed, wetted (RH ≈ 95%), swollen (24 h in water) and air-dried and heated (120 °C for 1 h) fibres were studied. Flax fibres have higher crystallinity, adsorption capacity (MB, CHX, water), and smaller MB desorption than cotton fibres. Cotton fibres have larger Vp value (nitrogen adsorption) and the SBET,N2 similar to that of flax. Water vapour adsorption is higher on flax since the adsorbed water volume is Vp,w = 0.19 and 0.14 cm3 g−1 for flax and cotton, respectively, at RH ≈ 95%. Wetted fibres are characterised by Vp,w larger by an order of magnitude than Vp,N2 for degassed samples because of swelling effect. However, nanopores at radius R < 1 nm are practically absent in all samples studied regardless of the characterisation technique. The adsorption of MB and CHX on flax fibres is much larger than that for cotton fibres. The specific surface area determined from MB adsorption is 51 m2 g−1 (close to SBET,w estimated from water adsorption but larger than SBET,N2) and 8 m2 g−1 (much smaller than SBET,N2 and SBET,w) for flax and cotton fibres, respectively.

Measurement of Pore Size and Porosity of Tissue Scaffolds

Tissue engineering involves seeding the patient’s cells on to a three-dimensional temporary scaffold. It is becoming increasingly obvious that cells used to seed the scaffold have very specific requirements concerning the morphology and chemistry of the surface of the scaffold and its interconnectivity. A range of techniques has been examined in relation to key measurements such as pore size and porosity. Since capillary flow porometry measures a pore solely at its most constricted point, the method is unable to provide characterisation of other aspects of the pore. Scanning Electron Microscopy is limited to examining surface pores in ‘stiff’ scaffolds. Although cryo-SEM reduces the amount of ice-induced damage generated in ‘soft’ scaffolds upon freezing, the technique is limited to the same constraints. Images produced via scanning confocal microscopy are probably more representative of the true structure of the scaffold than that implied by cryo-SEM, although due to the diffuse nature of the image it is difficult to measure pore sizes.

Competitive adsorption of macromolecules and real-time dynamics of Vroman-like effects

Quasi-elastic light scattering (QELS) and quartz crystal microbalance (QCM) non-equilibrium and equilibrium studies of competitive interactions of pairs of polymers and proteins with fumed silica and ceramic coatings deposited on QCM crystals show complex interfacial behaviour. The effects observed depend on the adsorption sequence of co-adsorbates, their chemical structure and the morphology and chemical structure of the adsorbent. The equilibrium adsorption and dynamics of interactions of macromolecules with bare adsorbent surface and surface covered with pre-adsorbed polymer or protein, are compared in terms of the distribution functions of the Gibbs free energy of adsorption, which varied from -25 kJ mol(-1) on a bare surface to almost 0 kJ mol(-1) on a polymer or protein coated surface.

Synthesis of the polymerizable room temperature ionic liquid AMPS – TEA and superabsorbency for organic liquids of its copolymeric gels with acrylamide

A polymerizable room temperature ionic liquid (RTIL), 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS) – triethylamine (TEA), was synthesized by neutralization of AMPS with TEA in acetone followed by evaporation of the solvent under a reduced pressure at room temperature. The RTIL was characterized with fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and 1H NMR. Co-polymeric gels of the RTIL with acrylamide (AAm) were prepared by aqueous solution polymerization using N,N′-methylenebisacrylamide as a crosslinker, and ammonium persulfate as an initiator. Superabsorbency of the gels in aqueous and a series of organic liquids was investigated gravimetrically. DSC data showed that the glass transition temperature of AMPS – TEA was −59.4 °C. Poly(AMPS – TEA-co-AAm) gels exhibited superabsorbency in both water and a series of organic solvents. The mechanism for swelling in aqueous and organic media of the gels was critically discussed.