Particle-mediated Histotripsy for the Targeted Treatment of Intraluminal Biofilms in Catheter-based Medical Devices

Date
2022-08-09Author
Childers, Christopher
Edsall, Connor
Mehochko, Isabelle
Mustafa, Waleed
Yuksel Durmaz, Yasemin
Klibanov, Alexander L.
Rao, Jayasimha
Vlaisavljevich, Eli
Metadata
Show full item recordAbstract
Objective: 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.
Impact Statement: CBMDs commonly become infected with bacterial biofilms leading to medical device failure, infection, and adverse patient outcomes.
Introduction: 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.
Methods: 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.
Results: 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.
Conclusion: 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.