Electrospun magnetic composite poly-3-hydroxybutyrate/magnetite scaffolds for biomedical applications: composition, structure, magnetic properties, and biological performance

Magnetically responsive composite polymer scaffolds have good potential for a variety of biomedical applications. In this work, electrospun composite scaffolds made of polyhydroxybutyrate (PHB) and magnetite (Fe3O4) particles (MPs) were studied before and after degradation in either PBS or a lipase solution. MPs of different sizes with high saturation magnetization were synthesized by the coprecipitation method followed by coating with citric acid (CA). Nanosized MPs were prone to magnetite-maghemite phase transformation during scaffold fabrication, as revealed by Raman spectroscopy; however, for CA-functionalized nanoparticles, the main phase was found to be magnetite, with some traces of maghemite. Submicron MPs were resistant to the magnetite-maghemite phase transformation. MPs did not significantly affect the morphology and diameter of PHB fibers. The scaffolds containing CA-coated MPs lost 0.3 or 0.2% of mass in the lipase solution and PBS, respectively, whereas scaffolds doped with unmodified MPs showed no mass changes after 1 month of incubation in either medium. In all electrospun scaffolds, no alterations of the fiber morphology were observed. Possible mechanisms of the crystalline-lamellar-structure changes in hybrid PHB/Fe3O4 scaffolds during hydrolytic and enzymatic degradation are proposed. It was revealed that particle size and particle surface functionalization affect the mechanical properties of the hybrid scaffolds. The addition of unmodified MPs increased scaffolds' ultimate strength but reduced elongation at break after the biodegradation, whereas simultaneous increases in both parameters were observed for composite scaffolds doped with CA-coated MPs. The highest saturation magnetization-higher than that published in the literature-was registered for composite PHB scaffolds doped with submicron MPs. All PHB scaffolds proved to be biocompatible, and the ones doped with nanosized MPs yielded faster proliferation of rat mesenchymal stem cells. In addition, all electrospun scaffolds were able to support angiogenesis in vivo at 30 days after implantation in Wistar rats

Nitric oxide synthase expression in AT receptor-deficient mice after DOCA-salt

Nitric oxide synthase expression in AT2 receptor–deficient mice after DOCA-salt.BackgroundAngiotensin II type 2 receptor–deficient mice (AT2-/y) provide an opportunity to study the relationship between the angiotensin II type 1 receptor (AT1) and nitric oxide synthase (NOS) isoforms without concomitant AT2 receptor–related effects. To test this relationship, the expression of renal NOS isoforms (neural, inducible, and endothelial) in AT2-/y and AT2+/y mice was examined. The mice were challenged with deoxycorticosterone acetate (DOCA)-salt to stimulate NO generation.MethodsGene expression analyses by real-time polymerase chain reaction (PCR) (TaqMan) were performed in kidneys to characterize neuronal nitric oxide synthase (nNOS), epithelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and the AT1 receptor. Pressure-natriuresis experiments were done to determine the physiologic background.ResultsAT2-/y mice showed nNOS and iNOS up-regulation. DOCA-salt increased iNOS expression more in AT2-/y mice than in AT2+/y mice. Immunohistochemistry localized the iNOS expression with DOCA-salt mainly in the glomeruli. eNOS was not different between the groups, and was not affected by DOCA-salt. DOCA-salt increased mean arterial pressure more in AT2-/y mice than in AT2+/y mice. Concomitantly, the pressure-natriuresis relationship was shifted to the right in AT2-/y and AT2+/y mice after DOCA-salt. DOCA-salt decreased renal blood flow (RBF) and glomerular filtration rate (GFR) in both groups. iNOS blockade did not lower blood pressure.ConclusionWe conclude that AT2 receptor deletion and concomitant up-regulation of the AT1 receptor is associated with up-regulation of nNOS and iNOS. Under DOCA-salt, renal iNOS expression was further increased. Because iNOS inhibition did not change blood pressure, iNOS may not be involved in the hemodynamics, but may contribute to organ damage

Cryo-Structuring of Polymeric Systems. Poly(Vinyl Alcohol)-Based Cryogels Loaded with the Poly(3-hydroxybutyrate) Microbeads and the Evaluation of Such Composites as the Delivery Vehicles for Simvastatin

Highly porous composite poly(vinyl alcohol) (PVA) cryogels loaded with the poly(3-hydroxybutyrate) (PHB) microbeads containing the drug, simvastatin (SVN), were prepared via cryogenic processing (freezing—storing frozen—defrosting) of the beads’ suspensions in aqueous PVA solution. The rigidity of the resultant composite cryogels increased with increasing the filler content. Optical microscopy of the thin section of such gel matrices revealed macro-porous morphology of both continuous (PVA cryogels) and discrete (PHB-microbeads) phases. Kinetic studies of the SVN release from the drug-loaded microbeads, the non-filled PVA cryogel and the composite material showed that the cryogel-based composite system could potentially serve as a candidate for the long-term therapeutic system for controlled drug delivery. Such PHB-microbeads-containing PVA-cryogel-based composite drug delivery carriers were unknown earlier; their preparation and studies have been performed for the first time