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Functionalized gold nanoparticles (AuNPs) have been widely investigated as promising multifunctional nanosystems for the theragnosis of lung cancer, the most common and prominent cause of cancer death worldwide. Nevertheless, nanoparticles are not in appropriate sizes for an accurate deep lung delivery and the lack of locally and effective delivery of therapeutic biomolecules to the deep lungs is, in fact, the major cause of low therapeutic outcome. Herein we incorporate, for the first time, AuNPs into respirable microparticles. AuNPs were functionalized with biocompatible oligo(2-oxazoline)-based optically stable fluorescent coatings, and conjugated with a laminin peptide (YIGSR) for targeted lung cancer delivery. These POxylated AuNPs were then incorporated into a chitosan matrix by a clean process, supercritical CO2-assisted spray drying (SASD), yielding nano-in-micro clean ultrafine dry powder formulations. The engineered formulations present the adequate morphology and flowability to reach the deep lung, with aerodynamic sizes ranging 3.2–3.8 μm, and excellent fine particle fraction (FPF) (FPF of 47% for CHT-bearing targeted AuNPs). The optimal biodegradation and release profiles enabled a sustained and controlled release of the embedded nanoparticles, with enhanced cellular uptake, opening new prospects for future lung theragnosis.

Quercus suber (cork oak) is an evergreen tree native to the Mediterranean basin, which plays a key role in the ecology and economy of this area. Over the last decades, this species has gone through an observable decline, mostly due to environmental factors. Deciphering the mechanisms of cork oak’s response to the environment and getting a deep insight into its biology are crucial to counteract biotic and abiotic stresses compromising the stability of a unique ecosystem. In the light of these setbacks, the publication of the genome in 2018 was a major step towards understanding the genetic make-up of this species. In an effort to integrate this information in a comprehensive, accessible and intuitive format, we have developed The Cork Oak Genome Database Portal (CorkOakDB). The CorkOakDB is supported by the BioData.pt e-infrastructure, the Portuguese ELIXIR node for biological data. The portal gives public access to search and explore the curated genomic and transcriptomic data on this species. Moreover, CorkOakDB provides a user-friendly interface and functional tools to help the research community take advantage of the increased accessibility to genomic information. A study case is provided to highlight the functionalities of the portal. CorkOakDB guarantees the update, curation and data collection, aiming to collect data besides the genetic/genomic information, in order to become the main repository in cork oak research. Database URL: http://corkoakdb.org/

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A common phenomenon in tissue engineering is rapid tissue formation on the outer edge of the scaffold which restricts cell penetration and nutrient exchange to the scaffold centre, resulting in a necrotic core. To address this problem, we generated scaffolds with both random and anisotropic open porous architectures to enhance cell and subsequent tissue infiltration throughout the scaffold for applications in bone and cartilage engineering. Hydroxyapatite (HA) and poly(D,L-lactic acid) (P(DL)LA) scaffolds with random open porosity were manufactured, using modified slip-casting and by supercritical fluid processing respectively, and subsequently characterised. An array of porous aligned channels (400 microm) was incorporated into both scaffold types and cell (human osteoblast sarcoma, for HA scaffolds; ovine meniscal fibrochondrocytes, for P(DL)LA scaffolds) and tissue infiltration into these modified scaffolds was assessed in vitro (cell penetration) and in vivo (tissue infiltration; HA scaffolds only). Scaffolds were shown to have an extensive random, open porous structure with an average porosity of 85%. Enhanced cell and tissue penetration was observed both in vitro and in vivo demonstrating that scaffold design alone can influence cell and tissue infiltration into the centre of tissue engineering scaffolds.

Microcellular foams were produced from polycaprolactone (PCL) using a method based on the rapid release of supercritical CO2. The average pore size in the structure was found to vary with the selected vent time and the final microstructure was a combination of open and closed cells. Thermal analysis showed that the degree of crystallinity of all foams was in the region of 70%. This was found to be consistent with the observation of lamellar textures on the inner surface of the pores. There was also a pronounced decrease in compressive modulus with increasing vent time and average pore size.

This paper describes recent progress made in the use of high pressure or supercritical fluids to process polymers into three-dimensional tissue engineering scaffolds. Three current examples are highlighted: foaming of acrylates for use in cartilage tissue engineering; plasticization and encapsulation of bioactive species into biodegradable polyesters for bone tissue engineering; and a novel laser sintering process used to fabricate three-dimensional biodegradable polyester structures from particles prepared via a supercritical route.

Cell adhesion and proliferation on poly(D,L-lactic acid) (PDLLA) tissue-engineering scaffolds is low. This is generally regarded to be due to the surface chemistry of the PDLLA polymer, although topographic features often worsen the situation. This study reports for the first time successful deposition of a plasma polymer throughout the porous network of a three-dimensional scaffold. This allylamine plasma deposit was used to improve cell adhesion on the PDLLA surface. X-ray photoelectron spectroscopy (XPS) analysis of sectioned scaffolds was used to demonstrate the penetration of nitrogen species to the inner surfaces and to compare the virgin PDLLA scaffold and the plasma polymer coated PDLLA scaffold with plasma-grafted allylamine. The nitrogen concentration at the exterior and interior scaffold surfaces was greater for the plasma deposits than for the grafted surfaces, and the chemical state of the incorporated surface nitrogen using the two methods was found to be different. Evaluation in vitro was carried out by studying 3T3 fibroblast attachment, morphology, and metabolic activity on the scaffolds. Cell activity and attachment was found to be greater for the plasma deposits than the plasma-grafted PDLLA scaffolds, and both were greater than for the virgin PDLLA scaffolds. It is concluded that plasma deposition is a viable method of increasing cell attachment throughout porous PDLLA scaffolds without changing the bulk characteristics of the polymer.

We describe the synthesis of new stabilizers for the free radical polymerization of methyl methacrylate in supercritical carbon dioxide. The stabilizers are based on commercially available copolymers containing maleic anhydride moieties. The maleic anhydride moieties undergo thermal ring opening in the presence of a fluorinated alcohol to form graft copolymers containing pendant fluorinated chains and carboxylic acid groups. We have investigated different polymer backbones to fabricate a range of materials that have been tested in scCO2 for their effectiveness as stabilizers. FTIR analysis indicates that the mode of stabilization is through an interaction between the carbonyl group of monomer (methyl methacrylate) and the carboxylic acid group of the stabilizer. Our results confirm that the correct choice of stabilizer backbone and fluorinated chain length leads to effective stabilization and production of poly(methyl methacrylate) in high yield, with an acceptable molecular weight, and with spherical par...

Lung cancer is one of the leading causes of death worldwide. Therefore, it is of extreme importance to develop new systems that can deliver anticancer drugs into the site of action when initiating a treatment. Recently, the use of nanotechnology and particle engineering has enabled the development of new drug delivery platforms for pulmonary delivery. In this work, POXylated strawberry-like gold-coated magnetite nanocomposites and ibuprofen (IBP) were encapsulated into a chitosan matrix using Supercritical Assisted Spray Drying (SASD). The dry powder formulations showed adequate morphology and aerodynamic performances (fine particle fraction 48%-55% and aerodynamic diameter of 2.6-2.8 µm) for deep lung deposition through the pulmonary route. Moreover, the release kinetics of IBP was also investigated showing a faster release of the drug at pH 6.8, the pH of lung cancer. POXylated strawberry-like gold-coated magnetite nanocomposites proved to have suitable sizes for cellular internalization and their fluorescent capabilities enable their future use in in vitro cell based assays. As a proof-of-concept, the reported results show that these nano-in-micro formulations could be potential drug vehicles for pulmonary administration.

Porous scaffold structures are used in tissue engineering to provide structural guidance for regenerating tissues. The use of carbon dioxide (CO2) to create such scaffolds has received some attention in the past but many researchers believe that although CO2 processing of polymers can lead to porous scaffolds there is limited interconnectivity between the pores. In this study, highly porous (greater than 85%) and well interconnected scaffolds were obtained in which the size, distribution and number of pores could be controlled. This control was achieved by altering the rate of venting from polymer discs saturated with CO2 under modest temperature and pressure. The polymer used is a blend of poly (ethyl methacrylate) and tetrahydrofurfuryl methacrylate (PEMA/THFMA). This polymer system has shown promise for potential applications in cartilage repair.

Supercritical carbon dioxide (scCO2) is a unique solvent with a wide range of interesting properties. This review focuses upon recent advances in the use of scCO2 in materials synthesis and materials processing. In particular, we consider the advances made in three major areas. First the design and application of new surfactants for use in scCO2, which enable the production of metal nanoparticles, porous polymers and polymers of high molecular weight with excellent morphology. Second the development of new polymer processing and polymer blend technologies in scCO2, which enable the synthesis of some very complex polymer composites and blends. Finally, the application of scCO2 in the preparation of novel biomedical materials, for example biodegradable polymer particles and scaffolds. The examples described here highlight that scCO2 allows facile synthesis and processing of materials, leading to new products with properties that would otherwise be very difficult to achieve.