Laser-ultrasonic delivery of agents into articular cartilage

Abstract Research is ongoing to develop drug therapies to manage osteoarthritis (OA) and articular cartilage (AC) injuries. However, means to deliver drug to localized AC lesions are highly limited and not clinically available. This study investigates the capability of laser ultrasound (laser-induce...

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Main Authors: Heikki J. Nieminen, Gonçalo Barreto, Mikko A. Finnilä, Alejandro García-Pérez, Ari Salmi, Sanjeev Ranjan, Kari K. Eklund, Kenneth P. H. Pritzker, Simo Saarakkala, Edward Hæggström
Format: Article
Language:English
Published: Nature Portfolio 2017-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-04293-5
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author Heikki J. Nieminen
Gonçalo Barreto
Mikko A. Finnilä
Alejandro García-Pérez
Ari Salmi
Sanjeev Ranjan
Kari K. Eklund
Kenneth P. H. Pritzker
Simo Saarakkala
Edward Hæggström
author_facet Heikki J. Nieminen
Gonçalo Barreto
Mikko A. Finnilä
Alejandro García-Pérez
Ari Salmi
Sanjeev Ranjan
Kari K. Eklund
Kenneth P. H. Pritzker
Simo Saarakkala
Edward Hæggström
author_sort Heikki J. Nieminen
collection DOAJ
description Abstract Research is ongoing to develop drug therapies to manage osteoarthritis (OA) and articular cartilage (AC) injuries. However, means to deliver drug to localized AC lesions are highly limited and not clinically available. This study investigates the capability of laser ultrasound (laser-induced plasma sound source) to deliver agents (methylene blue, MB, in PBS) into bovine AC. Treatment samples (n = 10) were immersed in MB solution simultaneously with LU exposure, while adjacent control 1 tissue (n = 10) was pre-treated with LU followed by immersion in MB and adjacent control 2 tissue (n = 10) was only immersed in MB. AC exposed (n = 22) or not exposed (n = 27) to LU were characterized for anomalies in structure, composition, viability or RNA expression. Optically detected MB content was significantly (p < 0.01) higher in treatment samples up to a depth of 500 µm from AC surface as compared to controls. No major unwanted short-term effects on AC structure, proteoglycan or collagen contents, chondrocyte viability or RNA expression levels were detected. In conclusion, LU can deliver agents into AC without major short-term concerns on safety. LU could reveal new strategies for the development of localized drug therapies in AC.
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spelling doaj.art-4c04c73ebf2b43d4b65dd64e478ad4142022-12-21T21:51:45ZengNature PortfolioScientific Reports2045-23222017-06-017111210.1038/s41598-017-04293-5Laser-ultrasonic delivery of agents into articular cartilageHeikki J. Nieminen0Gonçalo Barreto1Mikko A. Finnilä2Alejandro García-Pérez3Ari Salmi4Sanjeev Ranjan5Kari K. Eklund6Kenneth P. H. Pritzker7Simo Saarakkala8Edward Hæggström9Electronics Research Laboratory, Department of Physics, University of HelsinkiOrton Orthopaedic Hospital and Research Institute, Invalid FoundationResearch Group of Medical Imaging, Physics and Technology, Faculty of Medicine, University of OuluElectronics Research Laboratory, Department of Physics, University of HelsinkiElectronics Research Laboratory, Department of Physics, University of HelsinkiLaboratory of Radiochemistry, Department of Chemistry, University of HelsinkiDepartment of Rheumatology, University of Helsinki and Helsinki University HospitalDepartment of Laboratory Medicine and Pathobiology, University of TorontoResearch Group of Medical Imaging, Physics and Technology, Faculty of Medicine, University of OuluElectronics Research Laboratory, Department of Physics, University of HelsinkiAbstract Research is ongoing to develop drug therapies to manage osteoarthritis (OA) and articular cartilage (AC) injuries. However, means to deliver drug to localized AC lesions are highly limited and not clinically available. This study investigates the capability of laser ultrasound (laser-induced plasma sound source) to deliver agents (methylene blue, MB, in PBS) into bovine AC. Treatment samples (n = 10) were immersed in MB solution simultaneously with LU exposure, while adjacent control 1 tissue (n = 10) was pre-treated with LU followed by immersion in MB and adjacent control 2 tissue (n = 10) was only immersed in MB. AC exposed (n = 22) or not exposed (n = 27) to LU were characterized for anomalies in structure, composition, viability or RNA expression. Optically detected MB content was significantly (p < 0.01) higher in treatment samples up to a depth of 500 µm from AC surface as compared to controls. No major unwanted short-term effects on AC structure, proteoglycan or collagen contents, chondrocyte viability or RNA expression levels were detected. In conclusion, LU can deliver agents into AC without major short-term concerns on safety. LU could reveal new strategies for the development of localized drug therapies in AC.https://doi.org/10.1038/s41598-017-04293-5
spellingShingle Heikki J. Nieminen
Gonçalo Barreto
Mikko A. Finnilä
Alejandro García-Pérez
Ari Salmi
Sanjeev Ranjan
Kari K. Eklund
Kenneth P. H. Pritzker
Simo Saarakkala
Edward Hæggström
Laser-ultrasonic delivery of agents into articular cartilage
Scientific Reports
title Laser-ultrasonic delivery of agents into articular cartilage
title_full Laser-ultrasonic delivery of agents into articular cartilage
title_fullStr Laser-ultrasonic delivery of agents into articular cartilage
title_full_unstemmed Laser-ultrasonic delivery of agents into articular cartilage
title_short Laser-ultrasonic delivery of agents into articular cartilage
title_sort laser ultrasonic delivery of agents into articular cartilage
url https://doi.org/10.1038/s41598-017-04293-5
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