Jarkko Leskinen

Ultrasound stimulation of bone and cartilage – Interactions in common in vitro and tissue engineering configurations

Opponent

Professor Chris Moonen, University Medical Center Utrecht, the Netherlands

Reviewers

Professor Diane Dalecki, University of Rochester, United States of America

Professor Chen Deng, University of Michigan, United States of America

Supervisors

Professor Kullervo Hynynen, Sunnybrook Health Sciences Centre, Toronto, Canada

Research Director Mikko Lammi, University of Eastern Finland, Finland

Therapeutic ultrasound is clinically used to accelerate bone fracture healing. It alleviates osteoarthritic pain and improves joint functionality in the form of physiotherapy. The combination of stem cell engineering and therapeutic ultrasound has potential to differentiate and stimulate cells in scaffolds. However, the exact ultrasound mechanism causing these effects is unclear. In vitro studies form the biological and physical bases for this technique, and also provide the environment wherein the engineered cell structures are exposed. Ultrasound stimulation may not be repeatable in common in vitro setups that are usually optimized for culturing and biochemical assays. This results in variation in the exposure, and may affect the properties of the engineered material. In this thesis, cartilage and bone cells were sonicated in in vitro systems. Ultrasound-induced temperature elevation was measured andthe stimulating effect of ultrasound was compared with temperature elevation alone. In addition, non-invasive acoustic and optical measurement methods were used to show the complex nature of in vitro sonications. Results indicated that ultrasound stimulation, not temperature rise alone, induces proteoglycan synthesis in primary bovine chondrocytes. Ultrasound activated Wnt/β-catenin signaling in human osteoblastic MG-63 cells through both the thermal and non-thermal routes. Thermocouple and infrared camera measurements showed that many configurations are likely to have ultrasound-induced temperature elevations. Ultrasound standing waves were generated in typical exposure conditions and were sensitive to setup details. Optical measurements indicated that guided Lamb waves are generated on the commercial cell wells. Our results indicate that ultrasound exposures in common in vitro configurations are complex and highly variable.

  1. Kopakkala-Tani M, Leskinen JJ, Karjalainen HM, Karjalainen T, Hynynen K, Töyräs J, Jurvelin JS, Lammi MJ: Ultrasound stimulates proteoglycan synthesis in bovine primary chondrocytes. Biorheology 43(3-4):271-282, 2006 [Pubmed] [Full text]

  2. Leskinen JJ, Karjalainen HM, Olkku A, Hynynen K, Mahonen A, Lammi MJ: Genome-wide microarray analysis of MG-63 osteoblastic cells exposed to ultrasound. Biorheology 45(3-4):345-354, 2008 [Pubmed] [Full text]
  3. Olkku A, Leskinen JJ, Lammi MJ, Hynynen K, Mahonen A: Ultrasound-induced activation of Wnt signaling in human MG-63 osteoblastic cells. Bone 47(2):320-330, 2010 [Pubmed] [Full text]
  4. Leskinen JJ, Hynynen K: Study of factors affecting the magnitude and nature of ultrasound exposure with in vitro set-ups. Ultrasound Med Biol 38(5): 777-794, 2012 [Pubmed] [Full text]
  5. Leskinen JJ, Olkku A, Mahonen A, Hynynen K: Nonuniform temperature rise in in vitro osteoblast ultrasound exposures with associated bioeffect. IEEE Trans Biomed Eng 61(3): 620-927, 2014 [Pubmed] [Full text]

Last updated January 29, 2019

Articles of the thesis