Development of an optically transparent, tendon-mimicking hydrogel for histotripsy

Abstract

Collagenous, anisotropic tissues such as tendon are resilient to liquefaction by histotripsy, despite verification of cavitation activity using B-mode imaging. In previous published work, dehydrated fibrin gels were shown to mimic tendon bubble dynamics but are limited in thickness due to high opacity. Here, we aim to fabricate a thicker, more optically transparent hydrogel possessing similar cavitation dynamics to tendon. Highly transparent collagen hydrogels (TeloCol®, 10 mg/mL) were fabricated, and axial sound speeds were measured to determine anisotropy. Hydrogels were then exposed to 1.5-MHz focused ultrasound with 10-ms pulses at 1-Hz for 60 s with p + =127 MPa, p− = 35 MPa. Cavitation activity was monitored with high-speed photography and passive cavitation imaging using a Philips/ATL L7-4 transducer and Vantage® ultrasound system. Despite exhibiting low degrees of anisotropy like other non-dehydrated gels (<1.2), peak cavitation energy was >20% lower than soft-tissue mimicking polyacrylamide. Additionally, both resilience to fractionation and transparency were notably improved compared to previously tested PureCol® collagen formulations. Different levels of collagen dehydration will be explored to further increase resilience to liquefaction and assess the role of water content in histotripsy fractionation. [Work supported by NIH R01EB032860.]