Gema Rodríguez

Cellular interactions of biodegradable nanorod arrays prepared by nondestructive extraction from nanoporous alumina

Biodegradable extracellular matrices (ECMs) consisting of mechanically stable arrays of aligned poly(lactide) nanorods (nanorod diameter ≈ 200 nm; lattice constant ≈ 500 nm) with areas up to 9 cm2 were prepared by nondestructive extraction from recyclable self-ordered nanoporous alumina hard templates. Fibroblasts formed dense tissue layers on the heparin/gelatin activated nanorod arrays, showed excellent adhesion and exhibited a highly elongated morphology such as in natural tissue. The synthetic approach reported here combining advantages of top-down lithography (well-defined topography) and self-assembly (low costs, high throughput, feature size in the 100 nm range) may yield ECMs for biomedical applications. Remarkably, on microrod arrays with four times larger feature sizes the fibroblasts were significantly less elongated and their proliferation was strongly reduced.

Biomimetic Ca‐P coatings incorporating bisphosphonates produced on starch‐based degradable biomaterials

In this study, sodium clodronate, a well-known therapeutic agent from the family of bisphosphonates (BPs), is incorporated in a biomimetic calcium phosphate (CaP) coating, previously formed on the surface of a starch-based biomaterial by a sodium silicate methodology, as a strategy to develop a site-specific drug delivery system for bone tissue regeneration applications. The effects on the resulting CaP coatings were evaluated in terms of morphology, chemistry, and structure. The dissolution of Ca and P from the coating and the release profiles of sodium clodronate was also assessed. As a preliminary approach, this first study also aimed at evaluating the effects of this BP on the viability of a human osteoblastic cell line since there is still little information available on the interaction between BPs and this type of cells. Sodium clodronate was successfully incorporated, at different doses, in the structure of a biomimetic CaP layer previously formed by a sodium silicate process. This type of BPs had a stimulatory effect on osteoblastic activity, particularly at the specific concentration of 0.32 mg/mL. It is foreseen that these coatings can, for instances, be produced on the surface of degradable polymers and then used for regulating the equilibrium on osteoblastic/osteoclastic activity, leading to a controlled regenerative effect at the interface between the biomaterial and bone.

Transannular cyclizations of 10-membered lactams: An easy route to isoquinoline alkaloids

Abstract Transannular cyclization of 10-membered ring lactams with hydriodic acid or fluoride gave tetrahydroprotoberberines or isoindolobenzazepines, respectively. The starting macrolactams were prepared by intramolecular addition of an aryl radical to a trimethylsilylacetylene.

New resorbable polymeric systems with antithrombogenic activity.

The synthesis and application as resorbable coatings of vascular grafts of a new polyacrylic derivative of Triflusal (2-acetyloxy-4-trifluoromethyl)benzoic acid, a commercial drug with antithrombogenic properties, are described. The high-molecular-weight polyacrylic system is rather stable in physiological conditions and provides a chemical support for the slow release of the pharmacologically active compound, Triflusal, or its main metabolite (2-hydroxy-4-trifluoromethyl)benzoic acid (HTB). Experiments of deposition and retention of platelets in static basal conditions using plasma-rich medium from blood of sheep, seem to indicate that the polymeric coating of the polyacrylic derivative of Triflusal improves the antiaggregating character for platelets of the surface of small-diameter vascular grafts without the application of other antithrombogenic drugs.

Thermosensitive Macroporous Cryogels Functionalized With Bioactive Chitosan/Bemiparin Nanoparticles

Thermosensitive macroporous scaffolds of poly(N-isopropylacrylamide) (polyNIPA) loaded with chitosan/bemiparin nanoparticles are prepared by the free radical polymerization in cryogenic conditions. Chitosan/bemiparin nanoparticles of 102 ± 6.5 nm diameter are prepared by complex coacervation and loaded into polyNIPA cryogels. SEM image reveal the highly porous structure of cryogels and the integration of nanoparticles into the macroporous system. Volume phase transition temperature (VPT) and total freezing water content of cryogels are established by differential scanning calorimetry, and their porosity is determined by image-NMR. Swelling of cryogels (above and below the VPT) is highly dependent on nanoparticles concentration. In vitro release profile of bemiparin from cryogel is highly modulated by the presence of chitosan. Bemiparin released from nanoparticles preserves its biological activity, as shown by the BaF32 cell proliferation assay. Cryogels are not cytotoxic for the human fibroblast cells and present excellent properties for application on tissue engineering and controlled release of heparin.

Polymeric active coatings with functionality in vascular applications

Copolymers containing functional groups with activity as antiaggregating agents for platelets, based on random chains of metacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)]benzoate, TH, and 2-acrylamido-2-metylpropanesulfonic acid, AMPS, with AMPS molar fractions ranging from 0.1 to 0.4, have been prepared. The spectroscopical characterization and the in vitro swelling behavior have been studied, as well as the surface free energy, showing the copolymers an appropriate surface properties from a haemocompatible point of view. Preliminary in vitro tests using human blood have shown a promising antiaggregating behavior.

Criogeles de Poli N-isopropilacrilamida Cargados con Nanopartículas de Quitosana y Bemiparina

Chitosan/bemiparin spherical nanoparticles with a diameter of 429 + 134 nm were obtained by a complex coacervation technique. Bemiparin release in PBS from nanoparticles at 37 °C was followed by HPLC. During the first 72 hours 28 % bemiparin was released. From then on release became very slow, reaching 33 % in 21 days. Poly N-isporopylacrylamide (p-NIPA) croygels were synthesized by free radical polymerization of NIPA under freezing conditions, using N-N’-methylenebisacrylamide as cross-linker. Cryogels were loaded with nanoparticles and freeze-dried. They exhibited thermoresponsive behavior swelling at 15°C , below the lower critical sloution temperature (LCST) of p -NIPA and de-swelling at 37 °C, above its LCST.