Supercritical CO2 assisted impregnation of ibuprofen on medium-chain-length polyhydroxyalkanoates (mcl-PHA)

This work is financed by national funds from FCT-Fundacao para a Ciencia e a Tecnologia, I.P., in the scope of the project UIDB/50006/2020 of the Associate Laboratory for Green Chemistry-LAQV, the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences-UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy-i4HB. Liane Meneses and Alexandre Paiva would like to acknowledge FCT for the financial support through SFRH/BD/148510/2019 and IF/01146/2015.In this work, we propose the utilization of scCO2 to impregnate ibuprofen into the mcl- PHA matrix produced by Pseudomonas chlororaphis subs. aurantiaca (DSM 19603). The biopolymer has adhesive properties, is biocompatible and has a melting temperature of 45 °C. Several conditions, namely, pressure (15 and 20 MPa) and impregnation time (30 min, 1 h and 3 h) were tested. The highest ibuprofen content (90.8 ± 6.5 mg of ibuprofen/gPHA) was obtained at 20 MPa and 40 °C, for 1 h, with an impregnation rate of 89 mg/(g.h). The processed mcl-PHA samples suffered a plasticization, as shown by the decrease of 6.5 °C in the Tg, at 20 MPa. The polymer’s crystallinity was also affected concomitantly with the matrices’ ibuprofen content. For all the impregnation conditions tested the release of ibuprofen from the biopolymer followed a type II release profile. This study has demonstrated that the mcl-PHA produced by P. chlororaphis has a great potential for the development of novel topical drug delivery systems.publishersversionpublishe

Early pseudoprogression following chemoradiotherapy in glioblastoma patients: the value of RANO evaluation

Early Pseudo-progression Following Chemoradiotherapy in Glioblastoma Patients: The Value of RANO EvaluationThe aim of this study was to determine the frequency of pseudoprogression in a cohort of glioblastoma (GBM) patients following radiotherapy/temozolomide (RT/TMZ) by comparing Macdonald criterial to Response Assessment in Neuro-Oncology (RANO) criteria. The impact on prognosis and survival analysis was also studied. Materials and Methods. All patients receiving RT/TMZ for newly diagnosed GBM from January 2005 to December 2009 were retrospectively evaluated, and demographic, clinical, radiographic, treatment, and survival data were reviewed. Updated RANO criteria were used for the evaluation of the pre-RT and post-RT MRI and compared to classic Macdonald criteria. Survival data was evaluated using the Kaplan-Meier and log-rank analysis. Results and Discussion. 70 patients were available for full radiological response assessment. Early progression was confirmed in 42 patients (60%) according to Macdonald criteria and 15 patients (21%) according to RANO criteria. Pseudoprogression was identified in 10 (23.8%) or 2 (13.3%) patients in Macdonald and RANO groups, respectively. Cumulative survival of pseudoprogression group was higher than that of true progression group and not statistically different from the non-progressive disease group. Conclusion. In this cohort, the frequency of pseudoprogression varied between 13% and 24%, being overdiagnosed by older Macdonald criteria, which emphasizes the importance of RANO criteria and new radiological biomarkers for correct response evaluation.The authors acknowledge Francisco Soares, MD, for statistical support

Pseudo scapula alata: a case report of a scapular osteochondroma

An osteochondroma is a type of cartilaginous tumour, that frequently affects long bones. In the scapula, although rare, this benign tumour is the most frequently encountered. The symptoms at this location are usually related to the mass effect that it can produce. Surgery is recommended when symptoms of compression, pain or an increase in size are noticed. The authors present a case of a 11 year-old-boy with an osteochondroma on the ventral surface of the scapula, that cause a pseudo winging of this bone and pain, with indication for surgical excision. Pseudo scapula alata should be differentiated from the true one, which is a dynamic dyskinesia. In the presence of this static deformity the surgeon must keep in mind other diagnosis as a scapular osteochondroma or other mass effect lesions. This benign tumour does not frequently suffer malignant transformation. Surgery can lead to a complete resolution of the symptoms, and if done properly decrease to almost zero the rate of recurrence. The diagnosis of the tumour in this location can be delayed due to its atypical location and presentation. With this case report the authors expect to raise awareness of the unusual manifestations of osteochondroma, especially in the paediatric setting.

Supercritical fluid processing of natural based polymers doped with ionic liquids

Some approaches have been developed in our group to investigate the role of ionic liquids as process and property modifiers of natural-based polymers. In our previous work, we proposed the use of ionic liquids as plasticizing agents for the creation of porous structures from a semi-crystalline natural-based polymer. The current work intended to complement the previous studies, evaluating the ability of ionic liquid (IL) to plasticize blends of starch with poly (lactic) acid, with different ratios of starch and PLA of 50:50 and 30:70, and its effect on supercritical fluid foaming process (SCF) and providing more insights on the mechanisms involved. For this purpose, SPLA blends were modified and processed using 1-butyl-3-methylimidazolium chloride ([bmim]Cl). Supercritical fluid foaming was studied at different soaking times (1, 3 and 6 h) using carbon dioxide at 20.0 MPa and 40 oC. The blends were characterized by different techniques, such as infra-red spectroscopy, differential scanning calorimetry and compression and tensile mechanical analysis. The morphology of the foamed structures was analyzed by scanning electron microscopy and micro-computed tomography. The results suggest that after 3h of soaking time an equilibrium state of carbon dioxide into the bulk samples is attained, yielding structures with 6% and 15% of porosity, for SPLA70 and SPLA50 respectively. The solubility of carbon dioxide withinthe matrices was studied for the same conditions and the results demonstrate a higher sorption degree in the samples doped with ionic liquid. Sorption and desorption diffusion coefficients of supercritical CO2 in the SPLA matrix were determined for the raw polymer and for the SPLA doped with [bmim]Cl. It was found that the lower desorption diffusion coefficients are related with the higher porosity obtained by the foaming process.The research leading to these results has received funding from Fundacao da Ciencia e Tecnologia (FCT) through the project ENIG-MA - PTDC/EQU-EPR/121491/2010 and from the European Union's Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. REGPOT-CT2012-316331-POLARIS. Marta Martins and Rita Craveiro are grateful for financial support from Fundacao da Ciencia e Tecnologia (FCT) through the Grants BIM/PTDC/EQUEPR/121491/2010/ENIGMA and PTDC/EQUEPR/12191/2010/ENIGMA

Preparation of β-glucan scaffolds by hydrogel foaming with supercritical CO2

New materials and processing techniques are being constantly developed for the production of scaffolds for tissue engineering applications. Traditionally, foaming of polymers with supercritical fluids is one of the procedures used to create porous matrices. However, this technique cannot be applied to hydrophilic polymers which suffer degradation below their melting temperature. Foaming of hydrogels is an alternative to conventional gas foaming for the processing of hydrophilic polymers by dissolution of supercritical CO2 in the water of the hydrogels [1]. Through a fast depressurization, a highly porous structure is obtained, which results in the foamed matrix of polymer after water removal. In this work, β-glucan aerogels are produced by hydrogel foaming with supercritical CO2. Among polysaccharides, β-glucans have not been widely explored yet for tissue engineering applications. Depending on their origin, they posses different structures and properties. In our study, hydrogels were created from barley and yeast β-glucans. The produced aerogels were characterized in terms of morphology, mechanical properties and degradation rate in physiological fluids.MINECO (CTQ2013-44143-R)MINECO and UVa for Cierva fellowship (JCI-2012-14992)

Preparation of barley and yeast β-glucan scaffolds by hydrogel foaming: evaluation of dexamethasone release

Porous polymeric materials are studied in tissue engineering, because they can act as support for cell proliferation and as drug delivery vehicles for regeneration of tissues. Hydrogel foaming with supercritical CO2 is a suitable alternative for the creation of these structures, since it avoids the use of organic solvents and high temperature in the processing. In this work, β-glucans were used as raw materials to create hydrogels due to their easily gelation and biological properties. The enhancement of porosity was generated by a fast decompression after keeping the hydrogels in contact with CO2. The effect of the processing conditions and type of β-glucan in the final properties was assessed regarding morphological and mechanical properties. Finally, the ability of these materials to sustainably deliver dexamethasone was evaluated. The scaffolds had good morphology and provided a controlled release, thus being suitable to be used as scaffolds and drug delivery vehicles.Authors acknowledge Ministerio de Economía y Competitividad (MINECO) through project CTQ2013-44143-R and project PIP 063/ 147181 from Fundación General of the University of Valladolid for financial support. M. Salgado thanks to Ministerio de Educación, Ciencia y Deporte (MECD) for her FPU and mobility grants. S. Rodríguez-Rojo acknowledges to MINECO and UVa for her Juan de la Cierva fellowship (JCI-2012-14992). The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS and from the project “Novel smart and biomimetic materials for innovative regenerative medicine approaches” RL1 − ABMR − NORTE-01-0124-FEDER-000016) co- financed by North Portugal Regional Operational Programme (ON.2–O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio

Subcritical carbon dioxide foaming of polycaprolactone for bone tissue regeneration

Accepted manuscriptThe preparation of three-dimensional polycaprolactone scaffolds using dense CO2 as foaming agent, without supercritical conditions, was evaluated in this study towards future applications in bone repair. Herein, 3D foams were obtained at 5.0 MPa and 45 °C. To induce bioactivity, β-tricalcium phosphate (β-TCP, 10 wt%) and dexamethasone (5 and 10 wt%) were dispersed in the scaffolds. Foams revealed a pore size range of 164–882 μm, 73–99% porosity and 79–99% interconnectivity, assessed by micro-computed tomography, and a Young modulus of 1.76–2.92 MPa. Dexamethasone did not impair morphology of the matrices in comparison with PCL+β-TCP, which presented a water uptake of nearly 100% after 14 days. A sustained release of dexamethasone was achieved over 35 days in physiologic solution. This study reports the feasibility of using dense CO2 to produce in one-step a porous matrix loaded with active agents opening new possibilities towards injectable systems for in situ foamingEuropean Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS. It was also funded by the project “Novel smart and biomimetic materials for innovative regenerative medicine approaches” (RL1-ABMR-NORTE-01-0124-FEDER-000016) co-financed by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF) and the project NORTE‐01‐0145‐FEDER‐000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement. The authors would like to acknowledge the funding of the project Associate Laboratory ICVS/3B’s, under grant agreement number POCI-01-0145-FEDER-007038 supported by FEDER, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT)info:eu-repo/semantics/publishedVersio

Current nanotechnology advances in diagnostic biosensors

Current diagnostics present challenges that are imposed by increased life expectancy in the worldwide population. These challenges are related, not only to satisfy the need for higher performance of diagnostic tests, but also to the capacity of creating pointâ ofâ care, wearable, multiplexing and implantable diagnostic platforms that will allow early detection, continuous monitoring and treatment of health conditions in a personalized manner. These health challenges are translated into technological issues that need to be solved with multidisciplinary knowledge. Nanoscience and technology play a fundamental role in the development of miniaturized sensors that are cheap, accurate, sensitive and consume less power. At nanometre scale, these materials possess higher volumeâ toâ surface ratio and display novel properties (composition, charge, reactive sites, physical structure and potential) that are exploited for sensing purposes. These nanomaterials can therefore be integrated into diagnostic sensing platforms allowing the creation of novel technologies that tackle current health challenges. These nanomaterialâ enhanced sensors are extremely diverse, since they use numerous types of materials, nanostructures and detection modes for a multitude of biomarkers. The purpose of this review is to summarize the current stateâ ofâ theâ art of nanomaterialâ enhanced sensors, emphasizing and discussing the diagnostic challenges that are addressed by the different engineering and nanotechnology approaches. This review also aims to identify the drawbacks of nanomaterialâ enhanced sensors, as well as point out future developmental directions.This research was funded by FCT- FUNDAÇÃO PARA A CIÊNCIA E TECNOLOGIA, grant numbers: PTDC/EMD-EMD/31590/2017 and PTDC/BTM-ORG/28168/2017

Alternative methodology for chitin/hydroxyapatite composites using ionic liquids and supercritical fluid technology

An alternative, green method was used to develop chitin-based biocomposite (ChHA) materials by an integrated strategy using ionic liquids, supercritical fluid drying, and salt leaching. ChHA matrices were produced by dissolving chitin in 1-butyl-methylimidazolium acetate along with salt and/or hydroxyapatite particles and then subsequent drying. The ChHA composite formed had a heterogeneous porous microstructure with 65%–85% porosity and pore sizes in the range of 100–300 µm. The hydroxyapatite was found to be well distributed within the composite structures and had a positive effect in the viability and proliferation of osteoblast-like cells, in vitro. Our findings indicate that these ChHA matrices have potential applications in bone tissue engineering.Simone S. Silva and Miguel Oliveira received financial support from the Portuguese Foundation for Science and Technology-FCT (Grant SFRH/BPD/45307/2008 and SFRH/BPD/21786/2009, respectively), "Fundo Social Europeu"-FSE, and "Programa Diferencial de Potencial Humano-POPH." This work was partially supported by the FEDER through POCTEP 0330_IBEROMARE_1_P and European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. KBBE-2010-266033 (project SPECIAL)