University of Oulu

Nieminen, H.J., Lampsijärvi, E., Barreto, G. et al. Localized delivery of compounds into articular cartilage by using high-intensity focused ultrasound. Sci Rep 9, 15937 (2019).

Localized delivery of compounds into articular cartilage by using high-intensity focused ultrasound

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Author: Nieminen, Heikki J.1,2,3; Lampsijärvi, Eetu1; Barreto, Gonçalo4,5;
Organizations: 1Electronics Research Laboratory, Department of Physics, University of Helsinki, Helsinki, Finland
2Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland
3Research Group of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
4Department of Medicine, University of Helsinki, Helsinki, Finland
5Orton Orthopaedic Hospital and Research Institute, Invalid Foundation, Helsinki, Finland
6Department of Chemistry - Radiochemistry, University of Helsinki, Helsinki, Finland
7Department of Rheumatology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
8Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
9Department of Laboratory Medicine and Pathobiology, University of Toronto and Mount Sinai Hospital, Toronto, Canada
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.8 MB)
Persistent link:
Language: English
Published: Springer Nature, 2019
Publish Date: 2020-04-22


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.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 9
Article number: 15937
DOI: 10.1038/s41598-019-52012-z
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
317 Pharmacy
Funding: Academy of Finland is acknowledged for funding this study (grants no. 253579, 268378 and 273571). We grateful to Ms. Krista Rahunen for conducting imaging for histology. We thank Lihakonttori Oy (Helsinki, Finland) and Veijo Votkin Oy (Helsinki, Finland) for providing the bovine joints. The funding sources are not associated with the scientific contents of the study.
Academy of Finland Grant Number: 268378
Detailed Information: 268378 (Academy of Finland Funding decision)
273571 (Academy of Finland Funding decision)
Copyright information: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit