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  • Dual-crosslinked injectable in situ forming Alginate/CaCl2/Pluronic F127/ α-Cyclodextrin hydrogels incorporating Doxorubicin and graphene-based nanomaterials for cancer chemo-photothermal therapy
    Publication . Gonçalves, Joaquim; Melo, Bruna Daniela Lopes ; Pouso, Manuel António do Rosário ; Correia, Ilídio Joaquim Sobreira ; de Melo-Diogo, Duarte
    Injectable in situ forming hydrogels have been emerging due to their capacity to perform the direct delivery of therapeutics into the tumor site with minimal off-target leakage. Particularly, physical crosslinked injectable in situ forming hydrogels are appealing due to their straightforward preparation that exploits the native jointing capabilities of specific polymers/materials. However, the features of these hydrogels (e.g., injectability, degradation, swelling) are strongly pre-determined by the physical interactions available on the selected polymers/ materials, occasionally yielding undesired outcomes. Thus, the combination of multiple physical crosslinking cues may allow the preparation of hydrogels with enhanced properties. In this work, a dual-crosslinked injectable in situ forming hydrogel was engineered by combining Pluronic F127/α-Cyclodextrin and Alginate/CaCl2 (i.e., combination of host-guest and electrostatic interactions), being loaded with Doxorubicin (chemotherapeutic drug) and Dopamine-reduced Graphene Oxide (photothermal nano-agent) for application in cancer chemophotothermal therapy. When compared to the single-crosslinked hydrogels, the dual-crosslinking contributed to the assembly of formulations with suitable injectability and improved degradation and water absorption behaviors. Moreover, the dual-crosslinked hydrogels presented a good photothermal capacity (ΔT ≈ 14 ◦C), leading to a 1.18-times enhanced Doxorubicin release. In in vitro cell-based studies, the dual-crosslinked hydrogels exhibited an excellent cytocompatibility towards healthy (normal human dermal fibroblasts) and breast cancer (MCF-7) cells. As importantly, the dual-crosslinked hydrogels were able to mediate a chemophotothermal effect that diminished the cancer cells’ viability to just 23 %. Overall, the developed dualcrosslinked injectable in situ forming hydrogels incorporating Doxorubicin and Dopamine-reduced Graphene Oxide are a promising macroscale system for breast cancer chemo-photothermal therapy.
  • Beeswax-enriched tricalcium phosphate/hydroxyapatite/sodium alginate/ thymol 3D-printed scaffolds for application in bone tissue engineering
    Publication . Francisco, Martinho Jorge ; Cabral, Cátia Solange Duarte; Calvinho, Paula Cristina Nunes Ferreira ; Correia, Ilídio Joaquim Sobreira ; Moreira, André Ferreira
    Tissue engineering, particularly bone tissue engineering (BTE), continues to pose significant challenges to modern medicine. In this work, a rapid prototyping technique was explored to create 3D scaffolds using a Fab@Home 3D-Plotter extruder. For that purpose, a novel composite mixture containing tricalcium phosphate (TCP), hydroxyapatite (HAp), sodium alginate (SA), beeswax (BW), and thymol (TM) was formulated. BW and TM resulted in 3D scaffolds with rougher surfaces and moderate hydrophilic profiles, properties crucial for mediating cell adhesion and proliferation. Moreover, the 3D scaffolds containing BW displayed a significant increase in compressive strength and Young modulus, being comparable to those exhibited by trabecular bone. TM loading prevented the establishment of Staphylococcus aureus and Escherichia coli infections, inhibiting bacterial adhesion and proliferation at the scaffolds' surface. Additionally, the cytocompatibility of the scaffolds was confirmed over 21 days, with the adhesion and proliferation of Human osteoblasts (hOB) at the scaffold's surfaces. Simultaneously, calcium and phosphate ions accumulated at the scaffolds' surface, forming apatite crystals. Therefore, this improved composite mixture showed promising results for being applied in BTE, not only facilitating hOB cell adhesion and proliferation but also avoiding bacterial infection, addressing a critical challenge in implant-based therapies.
  • Injectable and implantable hydrogels for localized delivery of drugs and nanomaterials for cancer chemotherapy: A review
    Publication . Pouso, Manuel António do Rosário ; Melo, Bruna Daniela Lopes ; Gonçalves, Joaquim; Louro, Ricardo; Mendonça, António; Correia, Ilídio Joaquim Sobreira ; de Melo-Diogo, Duarte
    Multiple chemotherapeutic strategies have been developed to tackle the complexity of cancer. Still, the outcome of chemotherapeutic regimens remains impaired by the drugs’ weak solubility, unspecific biodistribution and poor tumor accumulation after systemic administration. Such constraints triggered the development of nanomaterials to encapsulate and deliver anticancer drugs. In fact, the loading of drugs into nanoparticles can overcome most of the solubility concerns. However, the ability of systemically administered drug-loaded nanomaterials to reach the tumor site has been vastly overestimated, limiting their clinical translation. The drugs’ and drug-loaded nanomaterials’ systemic administration issues have propelled the development of hydrogels capable of performing their direct/local delivery into the tumor site. The use of these macroscale systems to mediate a tumor-confined delivery of the drugs/drugs-loaded nanomaterials grants an improved therapeutic efficacy and, simultaneously, a reduction of the side effects. The manufacture of these hydrogels requires the careful selection and tailoring of specific polymers/materials as well as the choice of appropriate physical and/or chemical crosslinking interactions. Depending on their administration route and assembling process, these matrices can be classified as injectable in situ forming hydrogels, injectable shear-thinning/selfhealing hydrogels, and implantable hydrogels, each type bringing a plethora of advantages for the intended biomedical application. This review provides the reader with an insight into the application of injectable and implantable hydrogels for performing the tumor-confined delivery of drugs and drug-loaded nanomaterials.
  • Renewable Photo-Cross-Linkable Polyester-Based Biomaterials: Synthesis, Characterization, and Cytocompatibility Assessment
    Publication . Cernadas, Maria Teresa; Pereira, João; Melo, Bruna Daniela Lopes ; de Melo-Diogo, Duarte; Correia, Ilídio Joaquim Sobreira ; Alves, Patrícia; Calvinho, Paula Cristina Nunes Ferreira
    TThe present work consist of the synthesis of photo-crosslinkable materials, based on unsaturated polyesters (UPs), synthesized from biobased monomers from renewable sources such as itaconic acid and 1,4- butanediol. The UPs were characterized to assess the influence of polycondensation reaction temperature and cross-linking time on their final properties. For this purpose, different UV irradiation exposure periods were tested. Homogeneous, uniform, and transparent films were obtained after 1, 3, and 5 min of UV exposure. These cross-linked films were then characterized. All materials presented high gel content, which was dependent on the reaction’s temperature. The thermal behaviors of the UPs were shown to be similar. In vitro hydrolytic degradation tests showed that the materials can undergo degradation in phosphate-buffered saline (PBS) at pH 7.4 and 37 °C, ensuring their biodegradability over time. Finally, to assess the applicability of the polyesters as biomaterials, their cytocompatibility was determined by using human dermal fibroblasts.
  • Flapping Airfoil Aerodynamics using Recurrent Neural Network
    Publication . Pereira, João A.; Camacho, Emanuel A. R.; Marques, Flávio D.; Silva, André
    The recent increase in interest in artificial intelligence and neural networks has stirred up various industries. Inevitably, its application will trickle down to the most fundamental studies, for instance, unsteady aerodynamics. The present paper serves the purpose of exploring the ability of a recurrent neural network to predict flapping airfoil aerodynamics, in particular the lift coefficient of a plunging NACA0012 airfoil. Thus, a neural network is designed and trained using motion parameters, such as motion frequency and effective angle of attack, to output the instantaneous lift coefficient over a plunging period. Training data is generated using a panel code (HSPM) for fast generation and early testing. Results show that the neural network can adequately predict the lift coefficient for various conditions, including plunging kinematics that are far from the training domain. Future work will build on this framework and extend it to other aerodynamic coefficients using CFD results and experiments, which should enhance the value of the estimates.
  • Dynamic Stall Mitigation Using a Deflectable Leading Edge: The IK30 Mechanism
    Publication . Camacho, Emanuel A. R.; Silva, A. R. R.; Marques, Flávio D.
    One major problem affecting rotor blade aerodynamics is dynamic stall, characterized by a series of events where transient vortex shedding negatively affects drag and lift, leading to abrupt changes in the wing’s pitching moment. The present work focuses on the mitigation of such effects by using a modified NACA0012 airfoil—the NACA0012-IK30 airfoil—previously used for thrust enhancement in flapping propulsion. An experimental rig is designed to study the advantages of a deflectable leading edge on a plunging and pitching wing, more specifically its influence on the aerodynamic coefficients over time. In the first stage, results indicate that the proposed IK30 mechanism does mitigate the stall effects under static conditions, with stall visualization data corroborating it. Regarding time-varying conditions, the data presents the adequacy of the proposed geometry under different plunging and pitching conditions, which, when correctly used, can mitigate or even eradicate the adverse effects of dynamic stall experienced, leading to significant drag reductions and modest lift enhancements. In the absence of a dynamic stall, the movable leading edge can also provide operational advantages, where it does not negatively affect drag or lift but can reduce the pitching moment intensity by indirectly shifting the pressure center. This study contributes to the long-standing discussion on how to mitigate the adverse effects of dynamic stall by providing an innovative yet simple solution.
  • Influence of aluminum nanoparticles in alternative fuel: Single droplet combustion experiments and modeling
    Publication . Ferrão, Inês; Mendes, Tomás; Mendes, Miguel; Moita, A. S.; Silva, A. R. R.
    In this work, the effect of adding aluminum nanoparticles on hydrotreated vegetable oil was investigated experimentally and numerically in terms of nanofuel stability and single droplet combustion. The purpose is to understand the phenomena related to isolated droplet combustion when metallic particles are added to a liquid biofuel. Falling droplet combustion experiments were conducted in a drop tube furnace at two different furnace temperatures (800 C and 1000 C) using a high-speed camera coupled with a high magnification lens to investigate the droplet size evolution as disruptive burning phenomena. In numerical terms, a simplified macroscopic model was developed to predict the burning behavior of isolated nanofuel droplets, considering hexadecane as a surrogate fuel for the biofuel. The results reveal that adding nanoparticles resulted in a departure from the -law. Moreover, an increase in the overall droplet burning rate was observed, and according to the numerical results, nanoparticle radiation absorption is the responsible mechanism. Micro-explosions occurred for all nanofuels, and this disruptive burning behavior substantially influenced the droplet lifetime.
  • Housekeeping System for Suborbital Vehicles: VIRIATO Mock-Up Vehicle Integration and Testing
    Publication . Rodrigues, Geraldo; Arribas, Beltran; Melício, Rui; Gordo, Paulo; Valério, Duarte; Casaleiro, J.; Silva, André
    The work presented in this paper regards the improvement of a housekeeping system for data acquisition of a suborbital vehicle (VIRIATO rocket or launcher). The specifications regarding the vehicle are presented and hardware is chosen accordingly, considering commercial off-the-shelf components. Mechanical and thermal simulations are performed regarding the designed system and a physical prototype is manufactured, assembled and programmed. Functional and field test results resorting to unmanned aerial vehicles, as well as the system’s integration within VIRIATO project’s mock-up vehicle, are presented. These tests demonstrate the viability of this system as an independent data acquisition system, and simulation results show that commercial off-the-shelf components have the capability of surviving expected launch environments.
  • Microstructural properties of Asian hornet nest paper-like materials: Preliminary step towards biomimicry materials for civil engineering applications
    Publication . Sedira, Naim; Pinto, Jorge; Gomes, Ana; Nepomuceno, Miguel; Pereira, Sandra
    This paper presents a comprehensive examination of the microstructure and mineralogy of the paper-like material found in Asian hornet nests (referred to as AHN P-LM) and the nearby tree leaves, utilising scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) and X-ray diffraction (XRD). The analysis conducted through SEM-EDS demonstrates that AHN P-LM is primarily composed of plant fragments, with slight traces of inorganic substances (such as CaOx). The thread-like morphologies observed in the SEM analysis, which are linked to the secretion of hornets, warrant attention due to their significance in understanding the microstructure of AHN P-LM. The presence of nitrogen (N) in the EDS analysis of AHN P-LM, in contrast to its absence in analysed leaves, strongly implies that the nitrogen originates from hornet saliva. Additionally, SEM-EDS analysis revealed the impact of chemical composition variations on colour differences within AHN P-LM. Furthermore, X-ray diffraction analysis on ash samples from AHN P-LM confirmed the presence of minerals such as quartz, lime, phlogopite, and microcline. These findings about mineral composition align closely with results obtained from SEM-EDS analyses, presenting various aspects related to understanding the structure and compositional makeup of AHN P-LM. Biomimicry principles can be applied to draw inspiration from the AHN P-LM for replication in the civil engineering field, facilitating innovative solutions. Understanding hornet behaviour and nest material composition is essential. Future outlook includes utilising these materials in wood construction, 3D printing for structural components, shelters, infrastructure repair, green building, and architectural innovation.
  • Development of dual-crosslinked Pluronic F127/Chitosan injectable hydrogels incorporating graphene nanosystems for breast cancer photothermal therapy and antibacterial applications
    Publication . Pouso, Manuel António do Rosário; Melo, Bruna L.; Gonçalves, Joaquim; Mendonça, António; Correia, I.J.; Diogo, Duarte de Melo
    Nanomaterials with responsiveness to near-infrared light can mediate the photoablation of cancer cells with an exceptional spatio-temporal resolution. However, the therapeutic outcome of this modality is limited by the nanostructures’ poor tumor uptake. To address this bottleneck, it is appealing to develop injectable in situ forming hydrogels due to their capacity to perform a tumor-confined delivery of the nanomaterials with minimal off-target leakage. In particular, injectable in situ forming hydrogels based on Pluronic F127 have been emerging due to their FDA-approval status, biocompatibility, and thermosensitive sol–gel transition. Nevertheless, the application of Pluronic F127 hydrogels has been limited due to their fast dissociation in aqueous media. Such limitation may be addressed by combining the thermoresponsive sol–gel transition of Pluronic F127 with other polymers with crosslinking capabilities. In this work, a novel dual-crosslinked injectable in situ forming hydrogel based on Pluronic F127 (thermosensitive gelation) and Chitosan (ionotropic gelation in the presence of NaHCO3), loaded with Dopamine-reduced graphene oxide (DOPA-rGO; photothermal nanoagent), was developed for application in breast cancer photothermal therapy. The dual-crosslinked hydrogel incorporating DOPA-rGO showed a good injectability (through 21 G needles), in situ gelation capacity and cytocompatibility (viability > 73 %). As importantly, the dual-crosslinking improved the hydrogel’s porosity and prevented its premature degradation. After irradiation with near-infrared light, the dual-crosslinked hydrogel incorporating DOPA-rGO produced a photothermal heating (ΔT ≈ 22 °C) that reduced the breast cancer cells’ viability to just 32 %. In addition, this formulation also demonstrated a good antibacterial activity by reducing the viability of S. aureus and E. coli to 24 and 33 %, respectively. Overall, the dual-crosslinked hydrogel incorporating DOPA-rGO is a promising macroscale technology for breast cancer photothermal therapy and antimicrobial applications.