Project Summary Soft connective tissues have remarkable mechanical functions, operating in the large deformation regime, showing highly nonlinear stress-strain response, and being physiologically under residual stress. Dysregulation of the tissue homeostatic state is associated with pathology, such as hypertrophic scar contracture and liver fibrosis. Progress in imaging modalities has opened a window into tissue kinematics in vivo in health and disease, for example high frequency ultrasound. Yet, measurement of mechanical properties in vivo remains out of reach. The state of the art in biomedical research remains ex vivo mechanical tests, which hinders progress in basic biomedical research towards understanding how tissues adapt mechanically in health and disease. Thus, for accurate measurement of the physiological mechanical environment of soft tissues, to better understand biomechanics of disease onset and progression, and eventually to improve diagnostics and treatment based on the evolving mechanics of soft tissue, new tools to measure mechanical properties in vivo are urgently needed. The objective of this proposal is to develop a novel remotely actuated deformable membrane to perform mechanical tests of soft tissue in vivo. We will develop a remotely actuated membrane capable of locally applying controlled stress fields to underlying tissue and measuring the ensuing deformation with high frequency ultrasound (Aim 1); develop a data-driven model of an active membrane adhered to a soft deformable substrate to enable parameter estimation from complex stress-strain data (Aim 2); and validate the technology on tissue phantoms, and murine skin and liver tissues ex vivo and in vivo (Aim 3). The work proposed here will result in a new technology to do in vivo mechanical tests of soft tissue, enabling progress of basic research in biomedical engineering. Development of this technology will open new possibilities to monitoring tissue mechanics in animal models of disease, expanding the current paradigm of kinematic tracking only. Our future work will continue in the direction of our long-term goal, towards development of implantable devices based on the same core technology proposed here.

Project Narrative This project will develop a new type of device and data-driven algorithm for characterization of tissue mechanical behavior and residual stress in situ. The current paradigm in biomedical research concerning the evolving mechanics of soft tissue in health and disease relies on in vivo kinematic data but only ex vivo mechanical tests. To enable the investigation of new research questions in tissue mechanics and mechanobiology, we will create thin remotely actuated membranes that can be attached to soft tissues and controlled with a magnetic field, together with new data-driven algorithms to process the resulting complex stress-strain field data to determine the underlying tissue properties.