Browsing by Subject "FABRICATION"

Sort by: Order: Results:

Now showing items 1-20 of 35
  • Ahmadian, Zainab; Rebelo Correia, Alexandra Maria; Hasany, Masoud; Figueiredo, Patricia; Dobakhti, Faramarz; Reza Eskandari, Mohammad; Hosseini, Seyed; Abiri, Ramin; Khorshid, Shiva; Hirvonen, Jouni; Santos, Hélder A.; Shahbazi, Mohammad-Ali (2021)
    Generation of reactive oxygen species, delayed blood clotting, prolonged inflammation, bacterial infection, and slow cell proliferation are the main challenges of effective wound repair. Herein, a multifunctional extracellular matrix‐mimicking hydrogel is fabricated through abundant hydrogen bonding among the functional groups of gelatin and tannic acid (TA) as a green chemistry approach. The hydrogel shows adjustable physicochemical properties by altering the concentration of TA and it represents high safety features both in vitro and in vivo on fibroblasts, red blood cells, and mice organs. In addition to the merit of facile encapsulation of cell proliferation‐inducing hydrophilic drugs, accelerated healing of skin injury is obtained through pH‐dependent release of TA and its multifaceted mechanisms as an antibacterial, antioxidant, hemostatic, and anti‐inflammatory moiety. The developed gelatin‐TA (GelTA) hydrogel also shows an outstanding effect on the formation of extracellular matrix and wound closure in vivo via offered cell adhesion sites in the backbone of gelatin that provide increased re‐epithelialization and better collagen deposition. These results suggest that the multifunctional GelTA hydrogel is a promising candidate for the clinical treatment of full‐thickness wounds and further development of wound dressing materials that releases active agents in the neutral or slightly basic environment of infected nonhealing wounds.
  • Sodupe-Ortega, Enrique; Sanz-Garcia, Andres; Pernia-Espinoza, Alpha; Escobedo-Lucea, Carmen (2018)
    Most of the studies in three-dimensional (3D) bioprinting have been traditionally based on printing a single bioink. Addressing the complexity of organ and tissue engineering, however, will require combining multiple building and sacrificial biomaterials and several cells types in a single biofabrication session. This is a significant challenge, and, to tackle that, we must focus on the complex relationships between the printing parameters and the print resolution. In this paper, we study the influence of the main parameters driven multi-material 3D bioprinting and we present a method to calibrate these systems and control the print resolution accurately. Firstly, poloxamer hydrogels were extruded using a desktop 3D printer modified to incorporate four microextrusion-based bioprinting (MEBB) printheads. The printed hydrogels provided us the particular range of printing parameters (mainly printing pressure, deposition speed, and nozzle z-offset) to assure the correct calibration of the multi-material 3D bioprinter. Using the printheads, we demonstrated the excellent performance of the calibrated system extruding different fluorescent bioinks. Representative multi-material structures were printed in both poloxamer and cell-laden gelatin-alginate bioinks in a single session corroborating the capabilities of our system and the calibration method. Cell viability was not significantly affected by any of the changes proposed. We conclude that our proposal has enormous potential to help with advancing in the creation of complex 3D constructs and vascular networks for tissue engineering.
  • Loeblein, Jochen; Lorson, Thomas; Komma, Miriam; Kielholz, Tobias; Windbergs, Maike; Dalton, Paul D.; Luxenhofer, Robert (2021)
    Additive manufacturing or 3D printing as an umbrella term for various materials processing methods has distinct advantages over many other processing methods, including the ability to generate highly complex shapes and designs. However, the performance of any produced part not only depends on the material used and its shape, but is also critically dependent on its surface properties. Important features, such as wetting or fouling, critically depend mainly on the immediate surface energy. To gain control over the surface chemistry post-processing modifications are generally necessary, since it' s not a feature of additive manufacturing. Here, we report on the use of initiator and catalyst-free photografting and photopolymerization for the hydrophilic modification of microfiber scaffolds obtained from hydrophobic medical-grade poly(epsilon-caprolactone) via melt-electrowriting. Contact angle measurements and Raman spectroscopy confirms the formation of a more hydrophilic coating of poly(2-hydroxyethyl methacrylate). Apart from surface modification, we also observe bulk polymerization, which is expected for this method, and currently limits the controllability of this procedure.
  • Ding, Yaping; Li, Wei; W. Schubert, Dirk; R. Boccaccini , Aldo; A. Roether , Judith; Santos, Hélder A. (2021)
    Electrospun organic/inorganic hybrid scaffolds have been appealing in tissue regeneration owing to the integrated physicochemical and biological performances. However, the conventional electrospun scaffolds with non-woven structures usually failed to enable deep cell infiltration due to the densely stacked layers among the fibers. Herein, through self-assembly-driven electrospinning, a polyhydroxybutyrate/poly(e-caprolactone)/58S sol-gel bioactive glass (PHB/PCL/58S) hybrid scaffold with honeycomb-like structures was prepared by manipulating the solution composition and concentration during a one-step electrospinning process. The mechanisms enabling the formation of self-assembled honeycomb-like structures were investigated through comparative studies using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) between PHB/PCL/58S and PHB/PCL/sol-gel silica systems. The obtained honeycomb-like structure was built up from nanofibers with an average diameter of 370 nm and showed a bimodal distribution of pores: large polygonal pores up to hundreds of micrometers within the honeycomb-cells and irregular pores among the nanofibers ranging around few micrometers. The cell-materials interactions were further studied by culturing MG-63 osteoblast-like cells for 7 days. Cell viability, cell morphology and cell infiltration were comparatively investigated as well. While cells merely proliferated on the surface of non-woven structures, MG-63 cells showed extensive proliferation and deep infiltration up to 100-200 mu m into the honeycomb-like structure. Moreover, the cellular spatial organization was readily regulated by the honeycomb-like pattern as well. Overall, the newly obtained hybrid scaffold may integrate the enhanced osteogenicity originating from the bioactive components, and the improved cell-material interactions brought by the honeycomb-like structure, making the new scaffold a promising candidate for tissue regeneration.
  • Ahmadian, Zainab; Rebelo Correia, Alexandra Maria; Hasany, Masoud; Figueiredo, Patricia; Dobakhti, Faramarz; Reza Eskandari, Mohammad; Hosseini, Seyed; Abiri, Ramin; Khorshid, Shiva; Hirvonen, Jouni; Santos, Hélder A.; Shahbazi, Mohammad-Ali (2021)
    Extracellular matrix‐mimicking hydrogels with antioxidant, hemostasis, and antibacterial properties offer translating avenues towards wound repair through the promotion of fibroblast proliferation. In article number 2001122 by Hélder A. Santos, Mohammad‐Ali Shahbazi, and co‐workers, hydrogen bonding among the functional groups of gelatin and tannic acid creates a biocompatible hydrogel, where the improvement of re‐epithelialization and collagen deposition are its main features to treat full‐thickness wounds.
  • Ren, Hao; Yang, Peng; Winnik, Francoise M. (2020)
    Azo dyes, such as azobenzene, are able to convert absorbed light into motion or deformation on the macroscopic scale on the basis of their remarkable ability to undergo repeatedly and in 100% yield reversibletrans-to-cisphotoisomerization. Current needs for multiresponsive and fast photoswitches have led to the development of heteroaryl azo dyes, such as azopyridine. This remarkable azo compound combines the photoresponse of the azo chromophore with the chemistry of the pyridine ring, in particular its responsiveness to changes in pH and its ability to form hydrogen- and halogen-bonds. This mini-review summarizes key features of the photoisomerization of polymer-tethered azopyridine in aqueous media and describes a few recent research accomplishments in emerging areas that have benefited of the fast thermalcis-to-transrelaxation characteristics of azopyridinium or H-bonded azopyridine. It also discusses the effects of the photoisomerization of azopyridine on the thermoresponsive properties of azopyridine-tethered heat-sensitive polymers. Overall, azopyridine is a highly versatile actuator to consider when designing photo/multiresponsive polymeric materials.
  • Gal-Or, Eran; Gershoni, Yaniv; Scotti, Gianmario; Nilsson, Sofia Märta Elisabeth; Saarinen, Jukka Kalle Samuel; Jokinen, Ville Petteri; Strachan, Clare Joanna; Boije af Gennäs, Per Gustav; Yli-Kauhaluoma, Jari Tapani; Kotiaho, Ahti Antti Tapio (2019)
    Additive manufacturing (3D printing) is a disruptive technology that is changing production systems globally. In addition, microfluidic devices are increasingly being used for chemical analysis and continuous production of chemicals. Printing of materials such as polymers and metals is already a reality, but additive manufacturing of glass for microfluidic systems has received minor attention. We characterize microfluidic devices (channel cross-section dimensions down to a scale of 100 mm) that have been produced by additive manufacturing of molten soda-lime glass in tens of minutes and report their mass spectrometric and Raman spectroscopic analysis examples. The functionality of a microfluidic glass microreactor is shown with online mass spectrometric analysis of linezolid synthesis. Additionally, the performance of a direct infusion device is demonstrated by mass spectrometric analysis of drugs. Finally, the excellent optical quality of the glass structures is demonstrated with in-line Raman spectroscopic measurements. Our results promise a bright future for additively manufactured glass microdevices in diverse fields of science.
  • Calligaris, Sonia; Plazzotta, Stella; Valoppi, Fabio; Anese, Monica (2018)
    Combinations of ultrasound (US) and high-pressure homogenization (HPH) at low-medium energy densities were studied as alternative processes to individual US and HPH to produce Tween 80 and whey protein stabilized nanoemulsions, while reducing the energy input. To this aim, preliminary trials were performed to compare emulsification efficacy of single and combined HPH and US treatments delivering low-medium energy densities. Results highlighted the efficacy of US-HPH combined process in reducing the energy required to produce nanoemulsions stabilized with both Tween 80 and whey protein isolate. Subsequently, the effect of emulsifier content (1-3% w/w), oil amount (10-20% w/w) and energy density (47-175 MJ/m(3)) on emulsion mean particle diameter was evaluated by means of a central composite design. Particles of 140-190 nm were obtained by delivering 175 MJ/m(3) energy density at emulsions containing 3% (w/w) Tween 80 and 10% (w/w) oil. In the case of whey protein isolate stabilized emulsions, a reduced emulsifier amount (1% w/w) and intermediate energy density (120 MJ/m(3)) allowed a minimum droplet size around 220-250 nm to be achieved. Results showed that, in both cases, at least 50% of the energy density should be delivered by HPH to obtain the minimum particle diameter.
  • Fridlund, C.; Lopez-Cazalilla, A.; Nordlund, K.; Djurabekova, F. (2021)
    Structures consisting of a single Si nanodot buried within an insulating nanometric SiO2 layer stacked between two Si layers show promising properties for room temperature operational single-electron transistors. Moreover, such structures are highly compatible with modern complementary metal-oxide semiconductor technologies. Metastable SiOx phase separates into a Si nanodot and insulating, homogeneous SiO2 during annealing, providing a solid path towards the desired structure. However, achieving the necessary amount of excessive Si, dissolved in the SiO2 for correct concentrations of SiOx, remains a technological challenge. In this work, we investigate ion-induced atom mixing in pre-built Si/SiO2/Si nanopillars, which is considered to be a technologically promising way to produce the necessary concentrations of spatially confined SiOx in a controlled manner. During the high-fluence ion irradiation, we notice a significant shortening of the nanopillar and preferential loss of O atoms. Both sputtering and nanoscale ion hammering are found to be the cause of the deformation. The ion-hammering effect on nanoscale is explained by multiple small displacements, strongly enhanced after the nanopillar was rendered completely amorphous. The methods presented here can be used to determine the ion-fluence threshold for sufficient atom mixing in spatially confined regions before the large structural deformations are formed.
  • Wester, Niklas; Mikladal, Bjorn F.; Varjos, Ilkka; Peltonen, Antti; Kalso, Eija; Lilius, Tuomas; Laurila, Tomi; Koskinen, Jari (2020)
    A disposable electrochemical test strip for the quantitative point-of-care (POC) determination of acetaminophen (paracetamol) in plasma and finger-prick whole blood was fabricated. The industrially scalable dry transfer process of single-walled carbon nanotubes (SWCNTs) and screen printing of silver were combined to produce integrated electrochemical test strips. Nafion coating stabilized the potential of the Ag reference electrode and enabled the selective detection in spiked plasma as well as in whole blood samples. The test strips were able to detect acetaminophen in small 40 mu L samples with a detection limit of 0.8 mu M and a wide linear range from 1 mu M to 2 mM, well within the required clinical range. After a simple 1:1 dilution of plasma and whole blood, a quantitative detection with good recoveries of 79% in plasma and 74% in whole blood was achieved. These results strongly indicate that these electrodes can be used directly to determine the unbound acetaminophen fraction without the need for any additional steps. The developed test strip shows promise as a rapid and simple POC quantitative acetaminophen assay.
  • Kiiski, Iiro; Ollikainen, Elisa; Artes, Sanna; Järvinen, Päivi; Jokinen, Ville; Sikanen, Tiina (2021)
    UDP-glucuronosyltransferases (UGTs), located in the endoplasmic reticulum of liver cells, are an important family of enzymes, responsible for the biotransformation of several endogenous and exogenous chemicals, including therapeutic drugs. However, the phenomenon of 'latency', i.e., full UGT activity revealed by disruption of the microsomal membrane, poses substantial challenges for predicting drug clearance based on in vitro glucuronidation assays. This work introduces a microfluidic reactor design comprising immobilized human liver microsomes to facilitate the study of UGT-mediated drug clearance under flow-through conditions. The performance of the microreactor is characterized using glucuronidation of 8-hydroxyquinoline (via multiple UGTs) and zidovudine (via UGT2B7) as the model reactions. With the help of alamethicin and albumin effects, we show that conducting UGT metabolism assays under flow conditions facilitates in-depth mechanistic studies, which may also shed light on UGT latency.
  • Nilsson, Sofia; Suriyanarayanan, Subramanian; Kathiravan, Subban; Yli-Kauhaluoma, Jari; Kotiaho, Tapio; Nicholls, Ian A. (2019)
    Significant enantioselective recognition has been achieved through the introduction of long range ordered and highly interconnected 300 nm diameter pores in molecularly imprinted polymer matrices.
  • Hasselmann, Sebastian; Hahn, Lukas; Lorson, Thomas; Schaetzlein, Eva; Sebastien, Isabelle; Beudert, Matthias; Luehmann, Tessa; Neubauer, Julia C.; Sextl, Gerhard; Luxenhofer, Robert; Heinrich, Doris (2021)
    In this study, a novel approach to create arbitrarily shaped 3D hydrogel objects is presented, wherein freeform two-photon polymerization (2PP) is enabled by the combination of a photosensitive hydrogel and an intrinsic support matrix. This way, topologies without physical contact such as a highly porous 3D network of concatenated rings were realized, which are impossible to manufacture with most current 3D printing technologies. Micro-Raman and nanoindentation measurements show the possibility to control water uptake and hence tailor the Young's modulus of the structures via the light dosage, proving the versatility of the concept regarding many scaffold characteristics that makes it well suited for cell specific cell culture as demonstrated by cultivation of human induced pluripotent stem cell derived cardiomyocytes.
  • Golda-Cepa, Monika; Riedlova, Kamila; Kulig, Waldemar; Cwiklik, Lukasz; Kotarba, Andrzej (2020)
    Interactions at the solid-body fluid interfaces play a vital role in bone tissue formation at the implant surface. In this study, fully atomistic molecular dynamics (MD) simulations were performed to investigate interactions between the physiological components of body fluids (Ca2+, HPO42-, H2PO4-, Na+, Cl-, and H2O) and functionalized parylene C surface. In comparison to the native parylene C (-Cl surface groups), the introduction of -OH, -CHO, and -COOH surface groups significantly enhances the interactions between body fluid ions and the polymeric surface. The experimentally observed formation of calcium phosphate nanocrystals is discussed in terms of MD simulations of the calcium phosphate clustering. Surface functional groups promote the clustering of calcium and phosphate ions in the following order: -OH > -CHO > -Cl (parent parylene C) approximate to -COO-. This promoting role of surface functional groups is explained as stimulating the number of Ca2+ and HPO42- surface contacts as well as ion chemisorption. The molecular mechanism of calcium phosphate cluster formation at the functionalized parylene C surface is proposed.
  • Li, Wei; Chen, Jian; Zhao, Shujie; Huang, Tianhe; Ying, Huiyan; Trujillo, Claudia; Molinaro, Giuseppina; Zhou, Zheng; Jiang, Tao; Liu, Wei; Li, Linwei; Bai, Yuancheng; Quan, Peng; Ding, Yaping; Hirvonen, Jouni; Yin, Guoyong; Santos, Helder A.; Fan, Jin; Liu, Dongfei (2022)
    High drug loading improves therapeutic efficacy and reduces side effects in drug delivery. Here, the authors use controlled diffusion of solvents to precipitate drug nanoparticles in polymer particles while the polymer is solidifying and demonstrate the particles for drug delivery in a spinal cord injury model. Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8-63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 mu g) within the limited administration volume (10 mu L) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.
  • Tähkä, Sari; Sarfraz, Jawad; Urvas, Lauri; Provenzani, Riccardo; Wiedmer, Susanne K.; Peltonen, Jouko; Jokinen, Ville; Sikanen, Tiina (2019)
    We introduce rapid replica molding of ordered, high-aspect-ratio, thiol-ene micropillar arrays for implementation of microfluidic immobilized enzyme reactors (IMERs). By exploiting the abundance of free surface thiols of off-stoichiometric thiol-ene compositions, we were able to functionalize the native thiol-ene micropillars with gold nanoparticles (GNPs) and these with proteolytic alpha-chymotrypsin (CHT) via thiol-gold interaction. The micropillar arrays were replicated via PDMS soft lithography, which facilitated thiol-ene curing without the photoinitiators, and thus straightforward bonding and good control over the surface chemistry (number of free surface thiols). The specificity of thiol-gold interaction was demonstrated over allyl-rich thiol-ene surfaces and the robustness of the CHT-IMERs at different flow rates and reaction temperatures using bradykinin hydrolysis as the model reaction. The product conversion rate was shown to increase as a function of decreasing flow rate (increasing residence time) and upon heating of the IMER to physiological temperature. Owing to the effective enzyme immobilization onto the micropillar array by GNPs, no further purification of the reaction solution was required prior to mass spectrometric detection of the bradykinin hydrolysis products and no clogging problems, commonly associated with conventional capillary packings, were observed. The activity of the IMER remained stable for at least 1.5 h (continuous use), suggesting that the developed protocol may provide a robust, new approach to implementation of IMER technology for proteomics research.
  • Liu, Dongfei; Lipponen, Katriina; Quan, Peng; Wan, Xiaocao; Zhan, Hongbo; Makilä, Ermei; Salonen, Jarno; Kostiainen, Risto; Hirvonen, Jouni; Kotiaho, Tapio; Santos, Helder A. (2018)
    By exploiting its porous structure and high loading capacity, porous silicon (PSi) is a promising biomaterial to fabricate protocells and biomimetic reactors. Here, we have evaluated the impact of physicochemical properties of PSi particles [thermally oxidized PSi, TOPSi; annealed TOPSi, AnnTOPSi; (3-aminopropyl) triethoxysilane functionalized thermally carbonized PSi, APTES-TCPSi; and thermally hydrocarbonized PSi, THCPSi] on their surface interactions with different phospholipids. All of the four phospholipids were similarly adsorbed by the surface of PSi particles, except for TOPSi. Among four PSi particles, TOPSi with hydrophilic surface and smaller pore size showed the weakest adsorption toward phosphatidylcholines. By increasing the pore size from roughly 12.5 to 18.0 nm (TOPSi vs AnnTOPSi), the quantity of phosphatidylcholines adsorbed by TOPSi was enhanced to the same level of hydrophilic APTES-TCPSi and hydrophobic THCPSi. The 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) exhibited the highest release ratio of phospholipids from all four PSi particles, and phosphatidylserine (DPPS) showed the lowest release ratio of phospholipids from PSi particles, except for TOPSi, which adsorbed less phospholipids due to the small pore size. There is consistency in the release extent of phospholipids from PSi particles and the isosteric heat of adsorption. Overall, our study demonstrates the importance of pore size and surface chemistry of PSi particles as well as the structure of phospholipids on their interactions. The obtained information can be employed to guide the selection of PSi particles and phospholipids to fabricate highly ordered structures, for example, protocells, or biomimetic reactors.
  • Lumen, Dave; Wang, Shiqi; Mäkilä, Ermei; Imlimthan, Surachet; Sarparanta, Mirkka; Rebelo Correia, Alexandra Maria; Haug, Christina Westerveld; Hirvonen, Jouni; Santos, Hélder A.; Airaksinen, Anu; Filtvedt, Werner; Salonen, Jarno (2021)
    Porous silicon (PSi) is a biocompatible and biodegradable material, which can be utilized in biomedical applications. It has several favorable properties, which makes it an excellent material for building engineered nanosystems for drug delivery and diagnostic purposes. One significant hurdle for commercial applications of PSi is the lack of industrial scale production of nanosized PSi particles. Here, we report a novel two-step production method for PSi nanoparticles. The method is based on centrifuge chemical vapor deposition (cCVD) of elemental silicon in an industrial scale reactor followed by electrochemical post-processing to porous particles. Physical properties, biocompatibility and in vivo biodistribution of the cCVD produced nanoparticles were investigated and compared to PSi nanoparticles conventionally produced from silicon wafers by pulse electrochemical etching. Our results demonstrate that the cCVD production provides PSi nanoparticles with comparable physical and biological quality to the conventional method. This method may circumvent several limitations of the conventional method such as the requirements for high purity monocrystalline silicon substrates as starting material and the material losses during the top-down milling process of the pulse-etched films to porous nanoparticles. However, the electroless etching required for the porosification of cCVD-produced nanoparticles limited control over the pore size, but is amenable for scaling of the production to industrial requirements.
  • Singh, Akanksha; Scotti, Gianmario; Sikanen, Tiina; Jokinen, Ville; Franssila, Sami (2014)
  • Jutila, Eveliina; Koivunen, Risto; Kiiski, Iiro; Bollström, Roger; Sikanen, Tiina; Gane, Patrick (2018)
    Cytochrome P450 (CYP) is a superfamily of enzymes in charge of elimination of the majority of clinically used drugs and other xenobiotics. This study focuses on the development of a rapid microfluidic lateral flow assay to study human phase I metabolism reactions mediated by CYP2A6 isoenzyme, the major detoxification route for many known carcinogens and drugs, with coumarin 7-hydroxylation, as the prototype model reaction. Assay fabrication utilizes custom-designed porous functionalized calcium carbonate (FCC) coatings and inkjet-printed fluid barriers. All materials used are novel and carefully chosen to preserve biocompatibility. The design comprises separate zones for reaction, separation and detection, and an absorbent pad to keep the assay wet for extended periods (up to 10 min) even when heated to physiological temperature. The concept enables CYP assays to be made at lower cost than conventional well-plate assays, while providing increased selectivity at equally high speed, owing to the possibility for simultaneous chromatographic separation of the reaction products from the reactants on the FCC coating. The developed concept provides a viable rapid prediction of the interaction risks related to metabolic clearance of drugs and other xenobiotics, and exemplifies a novel coating technology illustrating the opportunity to broaden application functionality.