Development of remotely actuated deformable membranes for in situ mechanical testing of soft tissue

项目摘要 软结缔组织具有显著的机械功能，工作在大变形区域， 表现出高度非线性的应力-应变响应，生理上处于残余应力状态。调控失调 组织的动态平衡状态与病理有关，如增生性瘢痕痉挛和肝脏 纤维化症。成像方式的进步为了解健康和疾病的活体组织运动学打开了一扇窗， 例如高频超声波。然而，活体机械性能的测量仍然遥不可及。 生物医学研究的最新状态仍然是体外机械试验，这阻碍了基础研究的进展 生物医学研究，旨在了解组织如何在健康和疾病中机械适应。因此，对于 准确测量软组织的生理力学环境，以便更好地了解 疾病发生和发展的生物力学，并最终改善诊断和治疗的基础上 迫切需要软组织力学演化的新工具来测量活体的力学性能。 该方案目的是开发一种新型的遥控驱动可变形膜 活体软组织的力学测试。我们将开发一种能够局部应用的远程驱动膜 控制下伏组织的应力场，并以高频测量随后的变形 超声波(目标1)；开发附着在柔软可变形衬底上的有源膜的数据驱动模型 能够从复杂的应力-应变数据中估计参数(目标2)；并在组织上验证该技术 体模、体外和体内小鼠皮肤和肝脏组织(目标3)。这里提出的工作将导致一个 软组织活体力学测试的新技术，使生物医学基础研究取得进展 工程学。这项技术的发展将为监测动物的组织力学提供新的可能性 疾病模型，仅扩展了当前运动学跟踪的范例。我们今后的工作将继续下去 我们长期目标的方向是基于相同核心的植入式设备的开发 这里提出的技术。

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.