Browsing by Author "Salmi, Ari"

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  • Comparison of traditional and ultrasound-enhanced electrospinning in fabricating nanofibrous drug delivery systems
    (2019-10-01) Hakkarainen, Enni; Kõrkjas, Arle; Laidmäe, Ivo; Lust, Andres; Semjonov, Kristian; Kogermann, Karin; Nieminen, Heikki J.; Salmi, Ari; Korhonen, Ossi; Haeggström, Edward; Heinämäki, Jyrki
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    We investigated nozzleless ultrasound-enhanced electrospinning (USES) as means to generate nanofibrous drug delivery systems (DDSs) for pharmaceutical and biomedical applications. Traditional electrospinning (TES) equipped with a conventional spinneret was used as a reference method. High-molecular polyethylene oxide (PEO) and chitosan were used as carrier polymers and theophylline anhydrate as a water-soluble model drug. The nanofibers were electrospun with the diluted mixture (7:3) of aqueous acetic acid (90% v/v) and formic acid solution (90% v/v) (with a total solid content of 3% w/v). The fiber diameter and morphology of the nanofibrous DDSs were modulated by varying ultrasonic parameters in the USES process (i.e., frequency, pulse repetition frequency and cycles per pulse). We found that the USES technology produced nanofibers with higher fiber diameter (402 ± 127 nm) than TES (77 ± 21 nm). An increase of a burst count in USES increased the fiber diameter (555 ± 265 nm) and the variation in fiber size. The slight-to-moderate changes in a solid state (crystallinity) were detected when compared the nanofibers generated by TES and USES. In conclusion, USES provides a promising alternative for aqueous-based fabrication of nanofibrous DDSs for pharmaceutical and biomedical applications.
  • Delivery of agents into articular cartilage with electric spark-induced sound waves
    (2018-10-16) Pérez, Alejandro García; Nieminen, Heikki J.; Finnilä, Mikko; Salmi, Ari; Pritzker, Kenneth P.H.; Lampsijärvi, Eetu; Paulin, Tor; Airaksinen, Anu J.; Saarakkala, Simo; Hæggström, Edward
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Localized delivery of drugs into articular cartilage (AC) may facilitate the development of novel therapies to treat osteoarthritis (OA). We investigated the potential of spark-gap-generated sound to deliver a drug surrogate, i.e., methylene blue (MB), into AC. In vitro experiments exposed bovine AC samples to either simultaneous sonication and immersion in MB (Treatment 1; n = 10), immersion in MB after sonication (Control 1; n = 10), solely immersion in MB (Control 2; n = 10), or neither sonication nor immersion in MB (Control 3; n = 10). The sonication protocol consisted of 1,000 spark-gap -generated pulses. Delivery of MB into AC was estimated from optical absorbance in transmission light microscopy. Optical absorbance was significantly greater in the treatment group up to 900 μm depth from AC surface as compared to all controls. Field emission scanning electron microscopy (FESEM), histological analysis, and digital densitometry (DD) of sonicated (n = 6) and non-sonicated (n = 6) samples showed no evidence of sonication-induced changes in proteoglycan content or collagen structure. Consequently, spark-gap -generated sound may offer a solution for localized drug delivery into AC in a non-destructive fashion. Further research on this method may contribute to OA drug therapies.
  • Evaluation of bone growth around bioactive glass S53P4 by scanning acoustic microscopy co-registered with optical interferometry and elemental analysis
    (2023-12) Holmström, Axi; Meriläinen, Antti; Hyvönen, Jere; Nolvi, Anton; Ylitalo, Tuomo; Steffen, Kari; Björkenheim, Robert; Strömberg, Gustav; Nieminen, Heikki J.; Kassamakov, Ivan; Pajarinen, Jukka; Hupa, Leena; Salmi, Ari; Hæggström, Edward; Lindfors, Nina C.
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Bioactive glass (BAG) is a bone substitute that can be used in orthopaedic surgery. Following implantation, the BAG is expected to be replaced by bone via bone growth and gradual degradation of the BAG. However, the hydroxyapatite mineral forming on BAG resembles bone mineral, not providing sufficient contrast to distinguish the two in X-ray images. In this study, we co-registered coded-excitation scanning acoustic microscopy (CESAM), scanning white light interferometry (SWLI), and scanning electron microscopy with elemental analysis (Energy Dispersive X-ray Spectroscopy) (SEM–EDX) to investigate the bone growth and BAG reactions on a micron scale in a rabbit bone ex vivo. The acoustic impedance map recorded by the CESAM provides high elasticity-associated contrast to study materials and their combinations, while simultaneously producing a topography map of the sample. The acoustic impedance map correlated with the elemental analysis from SEM–EDX. SWLI also produces a topography map, but with higher resolution than CESAM. The two topography maps (CESAM and SWLI) were in good agreement. Furthermore, using information from both maps simultaneously produced by the CESAM (acoustic impedance and topography) allowed determining regions-of-interest related to bone formation around the BAG with greater ease than from either map alone. CESAM is therefore a promising tool for evaluating the degradation of bone substitutes and the bone healing process ex vivo.
  • Localized delivery of compounds into articular cartilage by using high-intensity focused ultrasound
    (2019-12-01) Nieminen, Heikki J.; Lampsijärvi, Eetu; Barreto, Gonçalo; Finnilä, Mikko A.J.; Salmi, Ari; Airaksinen, Anu J.; Eklund, Kari K.; Saarakkala, Simo; Pritzker, Kenneth P.H.; Hæggström, Edward
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Localized delivery of drugs into an osteoarthritic cartilaginous lesion does not yet exist, which limits pharmaceutical management of osteoarthritis (OA). High-intensity focused ultrasound (HIFU) provides a means to actuate matter from a distance in a non-destructive way. In this study, we aimed to deliver methylene blue locally into bovine articular cartilage in vitro. HIFU-treated samples (n = 10) were immersed in a methylene blue (MB) solution during sonication (f = 2.16 MHz, peak-positive-pressure = 3.5 MPa, mechanical index = 1.8, pulse repetition frequency = 3.0 kHz, cycles per burst: 50, duty cycle: 7%). Adjacent control 1 tissue (n = 10) was first pre-treated with HIFU followed by immersion into MB; adjacent control 2 tissue (n = 10) was immersed in MB without ultrasound exposure. The MB content was higher (p < 0.05) in HIFU-treated samples all the way to a depth of 600 µm from AC surface when compared to controls. Chondrocyte viability and RNA expression levels associated with cartilage degeneration were not different in HIFU-treated samples when compared to controls (p > 0.05). To conclude, HIFU delivers molecules into articular cartilage without major short-term concerns about safety. The method is a candidate for a future approach for managing OA.
  • Practical realization of a sub-λ/2 acoustic jet
    (2019-12-01) Veira Canle, Daniel; Kekkonen, Tuukka; Mäkinen, Joni; Puranen, Tuomas; Nieminen, Heikki J.; Kuronen, Antti; Franssila, Sami; Kotiaho, Tapio; Salmi, Ari; Hæggström, Edward
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Studies in optics and acoustics have employed metamaterial lenses to achieve sub-wavelength localization, e.g. a recently introduced concept called ‘acoustojet’ which in simulations localizes acoustic energy to a spot smaller than λ/2. However previous experimental results on the acoustojet have barely reached λ/2-wide localization. Here we show, by simulations and experiments, that a sub-λ/2 wide localization can be achieved by translating the concept of a photonic jet into the acoustic realm. We performed nano- to macroscale molecular dynamics (MD) and finite element method (FEM) simulations as well as macroscale experiments. We demonstrated that by choosing a suitable size cylindrical lens, and by selecting the speed-of-sound ratio between the lens material(s) and the surrounding medium, an acoustic jet (‘acoustic sheet’) is formed with a full width at half maximum (FWHM) less than λ/2. The results show, that the acoustojet approach can be experimentally realized with easy-to-manufacture acoustic lenses at the macroscale. MD simulations demonstrate that the concept can be extended to coherent phonons at nanoscale. Finally, our FEM simulations identify some micrometer size structures that could be realized in practice. Our results may contribute to starting a new era of super resolution acoustic imaging: We foresee that jet generating constructs can be readily manufactured, since suitable material combinations can be found from nanoscale to macroscale. Tight focusing of mechanical energy is highly desirable in e.g. electronics, materials science, medicine, biosciences, and energy harvesting.
  • Ultrasound-enhanced electrospinning
    (2018-12-01) Nieminen, Heikki J.; Laidmäe, Ivo; Salmi, Ari; Rauhala, Timo; Paulin, Tor; Heinämäki, Jyrki; Hæggström, Edward
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Electrospinning is commonly used to produce polymeric nanofibers. Potential applications for such fibers include novel drug delivery systems, tissue engineering scaffolds, and filters. Electrospinning, however, has shortcomings such as needle clogging and limited ability to control the fiber-properties in a non-chemical manner. This study reports on an orifice-less technique that employs high-intensity focused ultrasound, i.e. ultrasound-enhanced electrospinning. Ultrasound bursts were used to generate a liquid protrusion with a Taylor cone from the surface of a polymer solution of polyethylene oxide. When the polymer was charged with a high negative voltage, nanofibers jetted off from the tip of the protrusion landed on an electrically grounded target held at a constant distance from the tip. Controlling the ultrasound characteristics permitted physical modification of the nanofiber topography at will without using supplemental chemical intervention. Possible applications of tailor-made fibers generated by ultrasound-enhanced electrospinning include pharmaceutical controlled-release applications and biomedical scaffolds with spatial gradients in fiber thickness and mechanical properties.