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Supercritical CO2 foamed polycaprolactone scaffolds for controlled delivery of 5-fluorouracil, nicotinamide and triflusal.

The manufacture of porous polycaprolactone (PCL) scaffolds containing three different drugs, namely 5-fluorouracil, nicotinamide and triflusal, was investigated in this work with the aim of obtaining bioactive systems with controlled drug delivery capabilities. The scaffolds were prepared by means of a supercritical CO2 (scCO2) foaming technique by optimizing the drug loading process. This was achieved by dissolving the drugs in organic solvents miscible with scCO2 and by mixing these drug/solvent solutions with PCL powder. The as prepared mixtures were further compressed to eliminate air bubbles and finally processed by the scCO2 foaming technique. ScCO2 saturation and foaming conditions were optimized to create the porosity within the samples and to allow for the concomitant removal of the organic solvents. Physical and chemical properties of porous scaffolds, as well as drug content and delivery profiles, were studied by HPLC. The results of this study demonstrated that the composition of the starting PCL/drug/solvent mixtures affected polymer crystallization, scaffold morphology and pore structure features. Furthermore, it was found that drug loading efficiency depended on both initial solution composition and drug solubility in scCO2. Nevertheless, in the case of highly scCO2-soluble drugs, such as triflusal, loading efficiency was improved by adding a proper amount of free drug inside of the pressure vessel. The drug delivery study indicated that release profiles depended mainly upon scaffolds composition and pore structure features.

A clean and effective supercritical carbon dioxide method for the host–guest synthesis and encapsulation of photoactive molecules in nanoporous matrices

The present work is concerned with host–guest processes in the micro- and mesoporous restricted spaces provided by silica aerogels and aluminosilicates. A supercritical carbon dioxide ship-in-a-bottle approach was used for the synthesis of photoactive molecules (triphenylpyrylium and dimethoxyltrityl cations) inside these nanoporous matrices. The resulting hybrid nanocomposites can act as stable and recoverable heterogeneous photocatalysts, having obvious advantages with respect to the more easily degraded organic cations frequently used in homogeneous catalysis. Two aspects of green chemistry are combined in this study to produce nanoporous materials loaded with cationic photosensitizers: (i) the use of supercritical carbon dioxide as a reaction medium in one-pot and as a zero waste technology, and (ii) the use of transparent high surface area nanoporous supports that are expected to be more effective for the target photoactive applications than traditional opaque microporous matrices.

A novel bio-safe phase separation process for preparing open-pore biodegradable polycaprolactone microparticles.

Open-pore biodegradable microparticles are object of considerable interest for biomedical applications, particularly as cell and drug delivery carriers in tissue engineering and health care treatments. Furthermore, the engineering of microparticles with well definite size distribution and pore architecture by bio-safe fabrication routes is crucial to avoid the use of toxic compounds potentially harmful to cells and biological tissues. To achieve this important issue, in the present study a straightforward and bio-safe approach for fabricating porous biodegradable microparticles with controlled morphological and structural features down to the nanometer scale is developed. In particular, ethyl lactate is used as a non-toxic solvent for polycaprolactone particles fabrication via a thermal induced phase separation technique. The used approach allows achieving open-pore particles with mean particle size in the 150-250 μm range and a 3.5-7.9 m(2)/g specific surface area. Finally, the combination of thermal induced phase separation and porogen leaching techniques is employed for the first time to obtain multi-scaled porous microparticles with large external and internal pore sizes and potential improved characteristics for cell culture and tissue engineering. Samples were characterized to assess their thermal properties, morphology and crystalline structure features and textural properties.

Bio-safe processing of polylactic-co-caprolactone and polylactic acid blends to fabricate fibrous porous scaffolds for in vitro mesenchymal stem cells adhesion and proliferation

In this study, the design and fabrication of porous scaffolds, made of blends of polylactic-co-caprolactone (PLC) and polylactic acid (PLA) polymers, for tissue engineering applications is reported. The scaffolds are prepared by means of a bio-safe thermally induced phase separation (TIPS) approach with or without the addition of NaCl particles used as particulate porogen. The scaffolds are characterized to assess their crystalline structure, morphology and mechanical properties, and the texture of the pores and the pore size distribution. Moreover, in vitro human mesenchymal stem cells (hMSCs) culture tests have been carried out to demonstrate the biocompatibility of the scaffolds. The results of this study demonstrate that all of the scaffold materials processed by means of TIPS process are semi-crystalline. Furthermore, the blend composition affected polymer crystallization and, in turn, the nano and macro-structural properties of the scaffolds. Indeed, neat PLC and neat PLA crystallize into globular and randomly arranged sub micro-size scale fibrous conformations, respectively. Concomitantly, the addition of NaCl particles during the fabrication route allows for the creation of an interconnected network of large pores inside the primary structure while resulted in a significant decrease of scaffolds mechanical response. Finally, the results of cell culture tests demonstrate that both the micro and macro-structure of the scaffold affect the in vitro hMSCs adhesion and proliferation.

Study of the morphology and texture of poly(ε-caprolactone)/polyethylene oxide blend films as a function of composition and the addition of nanofillers with different functionalities

Films of a blend of semi-crystalline polymers, namely poly(e-caprolactone) (PCL) and poly(ethylene oxide) (PEO), are prepared by casting drops of ethyl lactate (EL) polymer solutions onto a glass substrate. The goal of this work is to assess how the surface structure of the blend films can be controlled by: (i) varying the relative amounts of the polymeric components, and (ii) adding inorganic nanoparticles (NPs) with different functionality. Specifically, four types of NPs are used here: bare and silanized titanium dioxide, hydroxyapatite and aluminum–magnesium layered double hydroxide. All the films exhibit a segregated surface morphology, characterized by either PEO-rich domains dispersed in a PCL continuous phase or discrete PCL domains embedded in a PEO-rich phase, depending on the composition of the blend. Phase inversion occurs within the 30–40% range of PEO weight fraction. The incorporation of NPs to the starting polymeric solution is found to significantly affect the final blend morphology, leading to either a coarsening or a refinement of the polymer phases mainly according to the chemical affinity between the NPs and the suspending medium.

PCL–HA microscaffolds for in vitro modular bone tissue engineering

The evolution of microscaffolds and bone‐bioactive surfaces is a pivotal point in modular bone tissue engineering. In this study, the design and fabrication of porous polycaprolactone (PCL) microscaffolds functionalized with hydroxyapatite (HA) nanoparticles by means of a bio‐safe and versatile thermally‐induced phase separation process is reported. The ability of the as‐prepared nanocomposite microscaffolds to support the adhesion, growth and osteogenic differentiation of human mesenchymal stem cells (hMSCs) in standard and osteogenic media and using dynamic seeding/culture conditions was investigated. The obtained results demonstrated that the PCL–HA nanocomposite microparticles had an enhanced interaction with hMSCs and induced their osteogenic differentiation, even without the exogenous addition of osteogenic factors. In particular, calcium deposition, alizarin red assay, histological analysis, osteogenic gene expression and collagen I secretion were assessed. The results of these tests demonstrated the formation of bone microtissue precursors after 28 days of dynamic culture. These findings suggest that PCL–HA nanocomposite microparticles represent an excellent platform for in vitro modular bone tissue engineering. Copyright

An Unprecedented Stimuli‐Controlled Single‐Crystal Reversible Phase Transition of a Metal–Organic Framework and Its Application to a Novel Method of Guest Encapsulation

The flexibility and unexpected dynamic behavior of a third-generation metal-organic framework are described for the first time. The synthetic strategy is based on the flexibility and spherical shape of dipyridyl-based carborane linkers that act as pillars between rigid Co/BTB (BTB: 1,3,5-benzenetricarboxylate) layers, providing a 3D porous structure (1). A phase transition of the solid can be induced to generate a new, nonporous 2D structure (2) without any loss of the carborane linkers. The structural transformation is visualized by snapshots of the multistep single-crystal-to-single-crystal transformation by single-crystal and powder X-ray diffraction. Poor hydrogen bond acceptors such as MeOH, CHCl3 or supercritical CO2 induce such a 3D to 2D transformation. Remarkably, the transformation is reversible and the 2D phase 2 is further converted back into 1 by heating in dimethylformamide. The energy requirements involved in such processes are investigated using periodic density functional theory calculations. As a proof of concept for potential applications, encapsulation of C60 is achieved by trapping this molecule during the reversible 2D to 3D phase transition, whereas no adsorption is observed by straight solvent diffusion into the pores of the 3D phase.

Impact of solvents and supercritical CO2 drying on the morphology and structure of polymer-based biofilms

In the present work, two-dimensional systems based on biodegradable polymers such as poly(e-caprolactone) (PCL), poly(ethylene oxide) (PEO) and polylactic acid (PLA) are fabricated by means of a sustainable approach which consists in inducing phase separation in solutions of such polymers and “green” solvents, namely ethyl lactate (EL) and ethyl acetate (EA). The extraction of the solvent is promoted by a controlled drying process, which is performed in either air or supercritical CO2. The latter can indeed act as both an antisolvent, which favors the deposition of the polymer by forming a mixture with EL and EA, and a plasticizing agent, whose solvation and transport properties may considerably affect the microstructure and crystallinity of the polymer films. The morphological, topographical and crystalline properties of the films are tailored through a judicial selection of the materials and the processing conditions and assessed by means of thermal analyses, polarized optical microscopy, scanning elect...