Special Issue: Biopolymers in Drug Delivery and Regenerative Medicine

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Green Processing of Nanoporous Biodegradable Carriers of Bioactive Agents for Pharmaceutical and Biomedical Applications

Pharmaceutical and biomedical industries demand simple, safe and reproducible processing methods thus urging the development of novel straightforward manufacturing approaches. The product manufacturing by the green processing of admixtures and end-product would avoid long and costly purification (downstream) steps. In this work, the green supercritical fluid technology is used for the processing of nanoporous carriers (aerogels) for bioactive agents [1,2]. Aerogels in the form of one micron-sized particles were processed and loaded with a model bioactive compound (ketoprofen). Results show that the carrier has excellent textural properties (specific surface area of 200 m2/g) and a high loading capacity (7 wt.%) of the bioactive compound in the amorphous form. Release profile tests show the capacity of the carrier to modulate the drug release to the medium (PBS pH 7.4). The resulting material can be incorporated in the formulation of several pharmaceutical and biomedical products

Drones and Sensors Ecosystem to Maximise the “Storm Effects” in Case of CBRNe Dispersion in Large Geographic Areas

The advancements in the field of robotics, specifically in the aerial robotics, combined with technological improvements of the capability of drones, have increased dramatically the use of these devices as a valuable tool in a wide range of applications. From civil to commercial and military area, the requirements in the emerging application for monitoring complex scenarios that are potentially dangerous for operators give rise to the need of a more powerful and sophisticated approach. This work aims at proposing the use of swarm drones to increase plume detection, tracking and source declaration for chemical releases. The several advantages which this technology may lead to this research and application fields are investigated, as well as the research and technological activities to be performed to make swarm drones efficient, reliable, and accurate

BUILDING VULNERABILITY ASSESSMENT FOR EXPLOSIVE AND CBR TERRORIST ATTACKS

Assessing the vulnerabilities of a building/site for a specific threat is one of the key issues in the risk assessment process. A vulnerability is defined as any weakness that can be exploited by an aggressor to make an asset susceptible to damage. The purpose of the vulnerability assessment process discussed in this paper is to identify the main vulnerabilities which influence a building’s risk level when a specific explosive or chemical, biological, radiological (CBR) threat arises. Vulnerability assessments are designed to provide an in-depth analysis of the characteristics of a facility and its associated elements to identify building weaknesses and lack of redundancy, as well as to determine protective or corrective actions that can be designed or implemented to reduce building vulnerabilities. This work proposes an innovative building vulnerability assessment method (BVAM), comprised of three steps. The first step, building criticality analysis (BCA), seeks to verify the criticality of several building aspects elaborated from best practices on the analysis of building structure and function. The result of this BCA determines if critical building components or systems, designed for the deterrence, detection, and limitation of damages, can continue to function properly during a crisis, and to ensure the correct operation of the emergency systems. The second step aims at characterising the application of a given number of specific threats to the building. The third step focuses on a final assessment of the level of vulnerability associated with the various applied threats, for the specific building and the specific assets to be protected. This result is achieved by employing a proposed seven-level vulnerability scale. The result of the evaluation of the level of vulnerability can be used for the final risk assessment phase

Bioaerogels: Promising Nanostructured Materials in Fluid Management, Healing and Regeneration of Wounds

Wounds affect one’s quality of life and should be managed on a patient-specific approach, based on the particular healing phase and wound condition. During wound healing, exudate is produced as a natural response towards healing. However, excessive production can be detrimental, representing a challenge for wound management. The design and development of new healing devices and therapeutics with improved performance is a constant demand from the healthcare services. Aerogels can combine high porosity and low density with the adequate fluid interaction and drug loading capacity, to establish hemostasis and promote the healing and regeneration of exudative and chronic wounds. Bio-based aerogels, i.e., those produced from natural polymers, are particularly attractive since they encompass their intrinsic chemical properties and the physical features of their nanostructure. In this work, the emerging research on aerogels for wound treatment is reviewed for the first time. The current scenario and the opportunities provided by aerogels in the form of films, membranes and particles are identified to face current unmet demands in fluid managing and wound healing and regenerationThis work was carried out in the frame of COST Action CA18125 “Advanced Engineering and Research of aeroGels for Environment and Life Sciences (AERoGELS)”, funded by the European Commission. This work was supported by National Funds from Fundação para a Ciência e a Tecnologia (FCT), through project UIDB/50016/2020, and by Xunta de Galicia [ED431C 2020/17], MCIUN [RTI2018-094131-A-I00], Agencia Estatal de Investigación [AEI] and FEDER fundsS

Peribiliary glands as a niche of extra-pancreatic precursors yielding insulin-producing cells in experimental and human diabetes

Peribiliary glands (PBGs) are niches in the biliary tree and containing heterogeneous endodermal stem/progenitors cells that can differentiate, in vitro and in vivo, towards pancreatic islets. The aim of this study was to evaluate, in experimental and human diabetes, proliferation of cells in PBGs and differentiation of the biliary tree stem/progenitor cells (BTSCs) towards insulin-producing cells. Diabetes was generated in mice by intraperitoneal injection of a single dose of 200 mg/kg (N=12) or 120 mg/kg (N=12) of streptozotocin. Liver, pancreas and extrahepatic biliary trees were en bloc dissected and examined. Cells in PBGs proliferated in experimental diabetes, and their proliferation was greatest in the PBGs of the hepato-pancreatic ampulla, and inversely correlated with the pancreatic islet area. In rodents, the cell proliferation in PBGs was characterized by the expansion of Sox9-positive stem/progenitor cells that gave rise to insulin-producing cells. Insulin-producing cells were located mostly in PBGs in the portion of the biliary tree closest to the duodenum, and their appearance was associated with up-regulation of MafA and Gli1 gene expression. In patients with type 2 diabetes, PBGs at the level of the hepato-pancreatic ampulla contained cells showing signs of proliferation and pancreatic fate commitment. In vitro, high glucose concentrations induced the differentiation of human BTSCs cultures towards pancreatic beta cell fates. The cells in PBGs respond to diabetes with proliferation and differentiation towards insulin-producing cells indicating that PBG niches may rescue pancreatic islet impairment in diabetes. These findings offer important implications for the patho-physiology and complications of this disease. This article is protected by copyright. All rights reserved

Hazelnut (Corylus avellana l.) shells extract: Phenolic composition, antioxidant effect and cytotoxic activity on human cancer cell lines

Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE)/g of extract). Neolignans, lawsonicin and cedrusin, a cyclic diarylheptanoid, carpinontriol B, and two phenol derivatives, C-veratroylglycol, and β-hydroxypropiovanillone, were the main components of the extract (0.71%-2.93%, w/w). The biological assays suggested that the extract could be useful as a functional ingredient in food technology and pharmaceutical industry showing an in vitro scavenging activity against the radical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (EC50 = 31.7 µg/mL with respect to α-tocopherol EC50 = 10.1 µg/mL), and an inhibitory effect on the growth of human cancer cell lines A375, SK-Mel-28 and HeLa (IC50 = 584, 459, and 526 µg/mL, respectively). The expression of cleaved forms of caspase-3 and poly(ADP-ribose) polymerase-1 (PARP-1) suggested that the extract induced apoptosis through caspase-3 activation in both human malignant melanoma (SK-Mel-28) and human cervical cancer (HeLa) cell lines. The cytotoxic activity relies on the presence of the neolignans (balanophonin), and phenol derivatives (gallic acid), showing a pro-apoptotic effect on the tested cell lines, and the neolignan, cedrusin, with a cytotoxic effect on A375 and HeLa cells

Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells

Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cultured in a weightless and protected environment SGM produced by the Rotary Cell Culture System (Synthecon) and control condition in normal gravity (NG). Self-replication and differentiation toward mature cells were determined by culturing hBTSCs in Kubota's Medium (KM) and in hormonally defined medium (HDM) tailored for hepatocyte differentiation. The effects on the expression and cell exo-metabolome profiles of SMG versus NG cultures were analyzed. SMG promotes tridimensional (3D) cultures of hBTSCs and HepG2. Significative increase of stemness gene expression (p < 0.05) has been observed in hBTSCs cultured in SMG when compared to NG condition. At the same time, the expression of hepatocyte lineage markers in hBTSCs differentiated by HDM was significantly lower (p < 0.05) in SMG compared to NG, demonstrating an impaired capability of hBTSCs to differentiate in vitro toward mature hepatocytes when cultured in SMG condition. Furthermore, in HepG2 cells the SMG caused a lower (p < 0.05 vs controls) transcription of CYP3A4, a marker of late-stage (i.e. Zone 3) hepatocytes. Exo-metabolome NMR-analysis showed that both cell cultures consumed a higher amount of glucose and lower glutamate in SMG respect to NG (p < 0.05). Moreover, hBTSCs media cultures resulted richer of released fermentation (lactate, acetate) and ketogenesis products (B-hydroxybutyrate) in SGM (p < 0.05) than NG. While, HepG2 cells showed higher consumption of amino acids and release of ketoacids (3-Methyl-2-oxovalerate, 2-oxo-4-methyl-valerate) and formiate with respect to normogravity condition (p < 0.05). Based on our results, SMG could be helpful for developing hBTSCs-derived liver devices. In conclusion, SMG favored the formation of hBTSCs and HepG2 3D cultures and the maintenance of stemness contrasting cell differentiation; these effects being associated with stimulation of glycolytic metabolism. Interestingly, the impact of SMG on stem cell biology should be taken into consideration for workers involved in space medicine programs