We previously demonstrated that ultrasound can deliver molecules into AC non-destructively 18– 21. Because HIU can influence tissue in so many ways, it can provide a way to address targeted and localized release, deposition, and translation of drugs for therapeutic purposes. If the time-averaged ultrasound intensity is high, the absorbed ultrasound energy appears as heating, which can induce tissue edema 16 or thermal necrosis 17. during cavitation, can induce micro-streams or shear forces near the bubbles 12, which can lead to tissue permeabilization 13, 14 or if excess, to tissue emulsification 15. Importantly, HIU can palpate a material or translate particles and gas voids non-destructively 6, 11, 12 from a distance, e.g. When the ultrasound energy is absorbed into liquid, acoustic streaming may form 7, 10. when sound energy is absorbed into a medium, reflected from an acoustic interface or scattered from a particle or void, an acoustic radiation force is exerted 7– 9. at medium interfaces or inside objects 6, where the momentum of the wave is changed. A traveling ultrasound wave carries momentum, which is converted into a force e.g. High intensity ultrasound (HIU) provides a way to manipulate tissue from a distance in a non-invasive manner 5. At present, clinical methods to deliver a therapeutic compounds directly into a local OA cartilage lesion do not exist. In both approaches, the API may not reach the target cartilage tissue unless excessive doses, which may be toxic are administered. orally or locally as intra-articular injections. The active pharmaceutical ingredient (API) can be delivered systemically 4, e.g. However, methods to deliver therapeutic compounds into such lesions are still mostly unavailable. structural and compositional changes in articular cartilage (AC) and underlying bone 1, 2 The OA lesions can involve only limited areas of the cartilage 3. Pathogenetically OA exhibits changes in osteochondral tissue, i.e.
Osteoarthritis (OA) is one of the leading causes of disability worldwide. The method is a candidate for a future approach for managing OA. To conclude, HIFU delivers molecules into articular cartilage without major short-term concerns about safety. 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. 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%). In this study, we aimed to deliver methylene blue locally into bovine articular cartilage in vitro. High-intensity focused ultrasound (HIFU) provides a means to actuate matter from a distance in a non-destructive way. Localized delivery of drugs into an osteoarthritic cartilaginous lesion does not yet exist, which limits pharmaceutical management of osteoarthritis (OA).
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