ESTG - Artigos em revistas internacionais
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- 3D Photo-Fabrication for Tissue Engineering and Drug DeliveryPublication . Brás Pereira, Rúben Filipe; Bartolo, PauloThe most promising strategies in tissue engineering involve the integration of a triad of biomaterials, living cells, and biologically active molecules to engineer synthetic environments that closely mimic the healing milieu present in human tissues, and that stimulate tissue repair and regeneration. To be clinically effective, these environments must replicate, as closely as possible, the main characteristics of the native extracellular matrix (ECM) on a cellular and subcellular scale. Photo-fabrication techniques have already been used to generate 3D environments with precise architectures and heterogeneous composition, through a multi-layer procedure involving the selective photocrosslinking reaction of a light-sensitive prepolymer. Cells and therapeutic molecules can be included in the initial hydrogel precursor solution, and processed into 3D constructs. Recently, photo-fabrication has also been explored to dynamically modulate hydrogel features in real time, providing enhanced control of cell fate and delivery of bioactive compounds. This paper focuses on the use of 3D photo-fabrication techniques to produce advanced constructs for tissue regeneration and drug delivery applications. State-of-the-art photo-fabrication techniques are described, with emphasis on the operating principles and biofabrication strategies to create spatially controlled patterns of cells and bioactive factors. Considering its fast processing, spatiotemporal control, high resolution, and accuracy, photo-fabrication is assuming a critical role in the design of sophisticated 3D constructs. This technology is capable of providing appropriate environments for tissue regeneration, and regulating the spatiotemporal delivery of therapeutics.
- 3D printing of new biobased unsaturated polyesters by microstereo-thermal-lithographyPublication . Gonçalves, Filipa A. M. M.; Costa, Cátia S. M. F.; Fabela, Inês G. P.; Farinha, Dina; Faneca, Henrique; Simões, Pedro N.; Serra, Arménio C.; Bártolo, Paulo J.; Coelho, Jorge F. J.New micro three-dimensional (3D) scaffolds using biobased unsaturated polyesters (UPs) were prepared by microstereo-thermal-lithography (μSTLG). This advanced processing technique offers indubitable advantages over traditional printing methods. The accuracy and roughness of the 3D structures were evaluated by scanning electron microscopy and infinite focus microscopy, revealing a suitable roughness for cell attachment. UPs were synthesized by bulk polycondensation between biobased aliphatic diacids (succinic, adipic and sebacic acid) and two different glycols (propylene glycol and diethylene glycol) using fumaric acid as the source of double bonds. The chemical structures of the new oligomers were confirmed by proton nuclear magnetic resonance spectra, attenuated total reflectance Fourier transform infrared spectroscopy and matrix assisted laser desorption/ionization-time of flight mass spectrometry. The thermal and mechanical properties of the UPs were evaluated to determine the influence of the diacid/glycol ratio and the type of diacid in the polyester's properties. In addition an extensive thermal characterization of the polyesters is reported. The data presented in this work opens the possibility for the use of biobased polyesters in additive manufacturing technologies as a route to prepare biodegradable tailor made scaffolds that have potential applications in a tissue engineering area.
- 3D-printed multisampling holder for microcomputed tomography applied to life and materials science researchPublication . Vasconcelos, Isabel; Franco, Margarida; Pereira, Mário; Duarte, Isabel; Ginjeira, António; Alves, NunoThe aim of this work was to design, fabricate, test and validate a 3D-printed multisampling holder for multi-analysis by microcomputed tomography. Different raw materials were scanned by microcomputed tomography. The raw material chosen was used to fabricate the holder by 3D printing. To validate the multisampling holder, five teeth were filled with a high density-material and scanned in two ways: a single and a multisampling scan mode. For each tooth, the root canal filling volume, porosity volume, closed pore volume, and open pore volume were calculated and compared when the same tooth was scanned in the two sampling scan mode. ABSplus P430™ allowed a high transmission value (84.3 %), and then it was the polymeric material selected to fabricate the holder. In a single sampling scan mode, the scan duration for scanning five teeth was 87.42 min, contrasting with 21.51 min for a multisampling scan mode, which scanned five teeth at the same time. The scan duration time and the cost using a multisampling holder represented a reduction of 75 % and the data volume generated represented a reduction of 60 %. Comparing the two scan modes, the results also showed that the difference of root canal filling volume, porosity volume, closed pore volume, and open pore volume was not statistically significant (p > .05). The multisampling holder was validated to do multi-analysis by microcomputed tomography without significant loss of quantitative accuracy data, allowing a reduction in scan duration time, imaging cost, and data storage.
- Additive manufactured porous biomaterials targeting orthopedic implants: A suitable combination of mechanical, physical and topological propertiesPublication . Bartolomeu, F.; Dourado, N.; Pereira, F.; Alves, N.; Miranda, G.; Silva, F. S.Orthopedic implants are under incessant advancement to improve their interactions with surrounding bone tissue aiming to ensure successful outcomes for patients. A successful biological interaction between implant and surrounding bone depends on the combination of mechanical, physical and topological properties. Hence, Ti6Al4V cellular structures appear as very promising solutions towards the improvement of conventional orthopedic implants. This work addresses a set of fundamental tools that allow improving the design of Ti6Al4V cellular structures produced by Selective Laser Melting (SLM). Three-point bending tests were carried out to estimate the elastic modulus of the produced structures. Morphological analysis allowed to evaluate the dimensional differences that were noticed between the model CAD and the SLM structures. Finite element models (adjusted CAD) were constructed with the experimentally obtained dimensions to replicate the mechanical response of the SLM structures. Linear correlations were systematically found for the dimensions of the SLM structures as a function of the designed model CAD dimensions. This has also been observed for the measured porosities as a function of the designed CAD models. This data can be used in further FE analyses as design guidelines to help engineers fabricating near-net-shape SLM Ti6Al4V cellular structures. Besides, polished and sandblasted surface treatments performed on the Ti6Al4V cellular structures allowed to obtain suitable properties regarding roughness and wettability when compared to as-produced surfaces. The capillarity tests showed that all the analyzed Ti6Al4V structures are able to transport fluid along its structure. The cell viability tests demonstrate Ti6Al4V cellular structures SLM produced did not release toxic substances to the medium, indicating that these structures can assure a suitable environment for cells to proliferate and attach. This study proposes a design methodology for Ti6Al4V cellular structures, that owe suitable mechanical properties but also provide a proper combination of porosity, roughness, wettability, capillarity and cell viability, all of them relevant for orthopedic applications. A Ti6Al4V cellular structured hip implant prototype gathering the suitable features addressed in this study was successfully SLM-produced.
- Advances in phytochemical delivery systems for improved anticancer activityPublication . Lagoa, Ricardo; Silva, João; Rodrigues, Joaquim Rui; Bishayee, AnupamNatural compounds have significant anticancer pharmacological activities, but often suffer from low bioavailability and selectivity that limit therapeutic use. The present work critically analyzes the latest advances on drug delivery systems designed to enhance pharmacokinetics, targeting, cellular uptake and efficacy of anticancer phytoconstituents. Various phytochemicals, including flavonoids, resveratrol, celastrol, curcumin, berberine and camptothecins, carried by liposomes, nanoparticles, nanoemulsions and films showed promising results. Strategies to avoid drug metabolism, overcome physiological barriers and achieve higher concentration at cancer sites through skin, buccal, nasal, vaginal, pulmonary and colon targeted delivery are presented. Current limitations, challenges and future research directions are also discussed.
- AlineaGA - a genetic algorithm with local search optimization for multiple sequence alignmentPublication . Silva, Fernando José Mateus da; Pérez, Juan Manuel Sánchez; Pulido, Juan Antonio Gómez; Rodríguez, Miguel A. VegaThe alignment and comparison of DNA, RNA and Protein sequences is one of the most common and important tasks in Bioinformatics. However, due to the size and complexity of the search space involved, the search for the best possible alignment for a set of sequences is not trivial. Genetic Algorithms have a predisposition for optimizing general combinatorial problems and therefore are serious candidates for solving multiple sequence alignment tasks. Local search optimization can be used to refine the solutions explored by Genetic Algorithms. We have designed a Genetic Algorithm which incorporates local search for this purpose: AlineaGA. We have tested AlineaGA with representative sequence sets of the globin family. We also compare the achieved results with the results provided by T-COFFEE.
- Analysis of friction in the ejection of thermoplastic mouldingsPublication . Correia, Mário Simões; Miranda, Antonio Sousa; Oliveira, Marta Cristina; Capela, Carlos Alexandre; Pouzada, Antonio SergioThe ejection force of injection-moulded thermoplastics depends on the contact conditions at the moment of ejection. Replication of the polymer part surface occurs onto the mould surface during injection of the melt. Ejection takes place in a very short time, hence the static coefficient of friction must be considered for modelling the ejection process. To understand the contribution of the mechanisms involved in the friction during the ejection stage, a mixed approach was followed: analytical simulation of the ploughing, numerical simulation of the deformation, and experimental inference of the adhesion. The relevance of roughness, temperature and contact pressure in the coefficient of friction was evidenced.
- Analysis of manufacturing parameters on the shear strength of aluminium adhesive single-lap jointsPublication . Pereira, A. M.; Ferreira, J. M.; Antunes, F. V.; Bártolo, P. J.An experimental and numerical investigation into the shear strength behaviour of aluminium alloy adhesive lap joints was carried out in order to understand the effect of geometrical and manufacturing parameters on the strength of adhesive bonding joints, with the aim of optimizing shear strength. The adherend material used for the experimental tests was an aluminium alloy in the form of thin sheets, and the adhesive used was a high strength epoxy. Five surface treatments were studied. The surface treatments process using sodium dichromate-sulphuric acid etch (CSA) and abrasive polishing (AP) resulted in improved joint shear strength when compared to acetone cleaning (SW), caustic etch (CE), and Tucker's reagent etch (TR). The decrease in surface roughness was found to increase the shear strength of single-lap joints. An increase in adherend thickness and overlap length was found to increase shear strength which means that an increase in joint rigidity increases its strength. A numerical analysis was developed to explain the effect of the geometrical parameters on rotation angle, stress and strain fields, and failure load. An increase in adherend thickness and overlap length decreases the joint rotation angle, reducing the plastic strain peak and therefore increasing the failure load.
- Analyzing the evidence of an IPR take-off in China and IndiaPublication . Godinho, Manuel Mira; Ferreira, VítorBoth China and India have been experiencing a historical take-off in the use of intellectual property rights (IPR). In terms of trademark applications filed with domestic IP offices in 2009, the evidence demonstrates that China now ranks 1st worldwide and India 5th, while for patent filings China ranks 3rd worldwide and India ranks 9th. This performance is remarkable as both China and India experienced negligible demand for IPR protection as recently as two decades ago. The IPR take up trends in these two countries are analyzed in detail, highlighting the structure of patent and trademark demand since 1990. Specifically, the available series are broken down and analyzed according to: (i) national versus foreign origin of patents and trademarks; (ii) technological (IPC) and trademark (NICE) classes; and (iii) the major individual patent users in each country. The data used refers to applications in the Chinese and Indian IP offices although the demand from residents of these two countries in both the international and other national systems is also assessed. Beyond the existing momentum in IPR registrations by China and India and their capacity to maintain it into the near future, the paper addresses practical questions about the strategies, motives and benefits behind the current trends. In particular, we seek to evaluate the capacity of both China’s and India’s National Innovation Systems to internalize the potential returns of this increasing demand for IPR. The insight reached finds that should both China and India sustain their current IPR growth rates, they will be able to catch up with the most advanced economies within the time span of a few decades.
- Application of curcuminoids in inflammatory, neurodegenerative and aging conditions - Pharmacological potential and bioengineering approaches to improve efficiencyPublication . Lagoa, Ricardo; Rajan, Logesh; Violante, Cristiana; Babiaka, Smith B.; Marques da Silva, Dorinda; Kapoor, Bhupinder; Reis, Flávio; Atanasov, Atanas G.Curcumin, a natural compound found in turmeric, has shown promise in treating brain-related diseases and conditions associated with aging. Curcumin has shown multiple anti-inflammatory and brain-protective effects, but its clinical use is limited by challenges like poor absorption, specificity and delivery to the right tissues. A range of contemporary approaches at the intersection with bioengineering and systems biology are being explored to address these challenges. Data from preclinical and human studies highlight various neuroprotective actions of curcumin, including the inhibition of neuroinflammation, modulation of critical cellular signaling pathways, promotion of neurogenesis, and regulation of dopamine levels. However, curcumin’s multifaceted effects - such as its impact on microRNAs and senescence markers - suggest novel therapeutic targets in neurodegeneration. Tetrahydrocurcumin, a primary metabolite of curcumin, also shows potential due to its presence in circulation and its anti-inflammatory properties, although further research is needed to elucidate its neuroprotective mechanisms. Recent advancements in delivery systems, particularly brain-targeting nanocarriers like polymersomes, micelles, and liposomes, have shown promise in enhancing curcumin’s bioavailability and therapeutic efficacy in animal models. Furthermore, the exploration of drug-laden scaffolds and dermal delivery may extend the pharmacological applications of curcumin. Studies reviewed here indicate that engineered dermal formulations and devices could serve as viable alternatives for neuroprotective treatments and to manage skin or musculoskeletal inflammation. This work highlights the need for carefully designed, long-term studies to better understand how curcumin and its bioactive metabolites work, their safety, and their effectiveness.