Electronics Research Laboratory, Department of Physics, University of Helsinki, Helsinki, Finland.
Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.
Sci Rep. 2019 Nov 4;9(1):15937. doi: 10.1038/s41598-019-52012-z.
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.
局部递药进入骨关节炎软骨病变尚未实现，这限制了骨关节炎（OA）的药物治疗。高强度聚焦超声（HIFU）提供了一种远距离非破坏性作用于物质的手段。在这项研究中，我们旨在将亚甲蓝局部递送至牛关节软骨中。HIFU 处理的样本（n=10）在超声处理期间（f=2.16MHz，峰正压=3.5MPa，机械指数=1.8，脉冲重复频率=3.0kHz，每脉冲串的周期：50，占空比：7%）浸泡在亚甲蓝（MB）溶液中。相邻的对照 1 组织（n=10）首先用 HIFU 预处理，然后浸泡在 MB 中；相邻对照 2 组织（n=10）浸泡在 MB 中而不进行超声暴露。与对照相比，HIFU 处理的样本在距离 AC 表面 600µm 深度处的 MB 含量均更高（p<0.05）。与对照相比，HIFU 处理的样本中的软骨细胞活力和与软骨退化相关的 RNA 表达水平没有差异（p>0.05）。总之，HIFU 可将分子递送至关节软骨中，而不会对安全性产生重大短期担忧。该方法是未来治疗 OA 的一种候选方法。
