Childers Christopher, Edsall Connor, Mehochko Isabelle, Mustafa Waleed, Durmaz Yasemin Yuksel, Klibanov Alexander L, Rao Jayasimha, Vlaisavljevich Eli
Virginia Tech Carilion School of Medicine, USA.
Department of Biomedical Engineering and Mechanics, Virginia Tech, USA.
BME Front. 2022 Jul 5;2022:9826279. doi: 10.34133/2022/9826279. eCollection 2022.
. This paper is an initial work towards developing particle-mediated histotripsy (PMH) as a novel method of treating catheter-based medical device (CBMD) intraluminal biofilms. . CBMDs commonly become infected with bacterial biofilms leading to medical device failure, infection, and adverse patient outcomes. . Histotripsy is a noninvasive focused ultrasound ablation method that was recently proposed as a novel method to remove intraluminal biofilms. Here, we explore the potential of combining histotripsy with acoustically active particles to develop a PMH approach that can noninvasively remove biofilms without the need for high acoustic pressures or real-time image guidance for targeting. . Histotripsy cavitation thresholds in catheters containing either gas-filled microbubbles (MBs) or fluid-filled nanocones (NCs) were determined. The ability of these particles to sustain cavitation over multiple ultrasound pulses was tested after a series of histotripsy exposures. Next, the ability of PMH to generate selective intraluminal cavitation without generating extraluminal cavitation was tested. Finally, the biofilm ablation and bactericidal capabilities of PMH were tested using both MBs and NCs. . PMH significantly reduced the histotripsy cavitation threshold, allowing for selective luminal cavitation for both MBs and NCs. Results further showed PMH successfully removed intraluminal biofilms in Tygon catheters. Finally, results from bactericidal experiments showed minimal reduction in bacteria viability. . The results of this study demonstrate the potential for PMH to provide a new modality for removing bacterial biofilms from CBMDs and suggest that additional work is warranted to develop histotripsy and PMH for treatment of CBMD intraluminal biofilms.
本文是将粒子介导的组织超声破碎术（PMH）开发为一种治疗基于导管的医疗设备（CBMD）腔内生物膜的新方法的初步工作。CBMD通常会被细菌生物膜感染，导致医疗设备故障、感染和不良患者预后。组织超声破碎术是一种非侵入性聚焦超声消融方法，最近被提议作为一种去除腔内生物膜的新方法。在此，我们探索将组织超声破碎术与声活性粒子相结合的潜力，以开发一种无需高声压或实时图像引导靶向即可非侵入性去除生物膜的PMH方法。测定了含有充气微泡（MBs）或充液纳米锥（NCs）的导管中的组织超声破碎术空化阈值。在一系列组织超声破碎术暴露后，测试了这些粒子在多个超声脉冲下维持空化的能力。接下来，测试了PMH在不产生腔外空化的情况下产生选择性腔内空化的能力。最后，使用MBs和NCs测试了PMH的生物膜消融和杀菌能力。PMH显著降低了组织超声破碎术的空化阈值，使MBs和NCs都能实现选择性腔内空化。结果进一步表明，PMH成功去除了泰贡导管内的腔内生物膜。最后，杀菌实验结果表明细菌活力的降低最小。本研究结果证明了PMH为从CBMDs中去除细菌生物膜提供新方式的潜力，并表明有必要开展更多工作来开发用于治疗CBMD腔内生物膜的组织超声破碎术和PMH。
