Targeting fibrin networks through mechanics-informed ultrasound-induced cavitation

Dense fibrous networks are hallmarks of pathological environments such as cancer stroma, wounds, and blood clots. They provide not only structural and functional support but also hinder drug transport. A major component of these networks is fibrin, a biopolymer that exhibits high extensibility and nonlinear strain-stiffening, making the matrix mechanically robust and resistant to disruption. Conventional mechanical or pharmacological methods often fail to alter or break these networks. While inertial cavitation has been shown to fragment tissues, it fails to break the fibrous networks. Here, we demonstrate that ultrasound-driven stable cavitation of microbubbles, informed by fibrin mechanics, can be engineered to penetrate and mechanically alter dense fibrin networks. Using high-speed imaging and microscale indentation, we identify the temporally evolving damage mechanisms induced during inertial and stable cavitation. We show that sustained forcing from stable cavitation leads to permanent reductions in matrix stiffness and enhances transport properties. These findings reveal that a stable cavitation-based strategy can be designed to potentially modulate fibrous biological materials.