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

Heikki J. Nieminen; Eetu Lampsijärvi; Gonçalo Barreto; Mikko A.J. Finnilä; Ari Salmi; Anu J. Airaksinen; Kari K. Eklund; Simo Saarakkala; Kenneth P.H. Pritzker; Edward Hæggström

doi:10.1038/s41598-019-52012-z

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

Heikki J. Nieminen^*, Eetu Lampsijärvi, Gonçalo Barreto, Mikko A.J. Finnilä, Ari Salmi, Anu J. Airaksinen, Kari K. Eklund, Simo Saarakkala, Kenneth P.H. Pritzker, Edward Hæggström

^*Corresponding author for this work

Department of Neuroscience and Biomedical Engineering

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Abstract

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.

Original language	English
Article number	15937
Pages (from-to)	1-9
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-52012-z
Publication status	Published - 1 Dec 2019
MoE publication type	A1 Journal article-refereed

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abstract = "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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AU - Salmi, Ari

AU - Airaksinen, Anu J.

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AU - Hæggström, Edward

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

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