Sensor-integrated 3D tissue scaffold for physiological interrogations

细胞和组织经常在体外的生存环境中培养，以促进疾病建模、药物测试和精准医学的各种研究。组织系统的力学和电行为是反映组织状态的两个基本生理特性。因此，在三维组织中实时监测这两个参数对于评估组织状态和揭示生物机制非常重要。全面的评估需要了解组织深处分布位置的两个参数，这仍然具有挑战性。该项目旨在将多功能生物电子传感器集成到3D大孔支架中，其中支架为组织培养提供3D微环境，而分布式和嵌入式传感器可以实时监测组织的电和机械响应。开发的系统可以导致更精确的生物医学设备用于疾病建模，药物筛选和健康诊断。外展工作预计将扩大STEM的参与和教育。跨学科的研究和培训将通过“创新挑战赛”为下一代年轻人准备创业经验。计划举办15 ~ 20名高中女生参加的“女工程师日”活动，并增加针对初高中女生的“Eureka”活动。了解深层组织中活细胞的生理和病理行为可以为疾病的生物学机制和生物医学解决方案提供基本的见解。传统的生物传感技术，如光学成像和平面生物芯片，往往局限于表面区域。为了超越这些限制，该项目旨在开发和验证一种新型的3D、传感器神经驱动的电子支架系统，该系统可以在工程组织中实现生物电学和生物力学信号的高速同时测量。核心方法是采用多级分层组件将多功能生物传感器集成到可编程的3D支架中。该系统将为细胞力学和电生理学的基础研究提供新的工具。这项研究还有望带来转化生物芯片，将目前的单参数、平面生理量化升级为工程组织中的多参数、深层组织生理量化。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Cells and tissues are often cultured outside the living environment (in vitro) to facilitate various studies in disease modeling, drug test and precision medicine. The mechanical and electrical behaviors of a tissue system are two basic physiological properties that indicate the tissue state. Consequently, the real-time monitoring of both parameters in the 3D tissue is important for assessing tissue state and revealing biological mechanisms. A comprehensive assessment requires the knowledge of both parameters at distributed locations buried deep in the tissue, which remains challenging. This project aims to integrate multifunctional bioelectronic sensors in a 3D macroporous scaffold, in which the scaffold provides a 3D microenvironment for tissue culturing whereas the distributed and embedded sensors can real-time monitor both electrical and mechanical responses from the tissue. The developed system can lead to more precise biomedical devices for disease modeling, drug screening, and health diagnostics. The outreach efforts are expected to broaden STEM participation and education. The interdisciplinary research and training will prepare next-generation young minds to entrepreneurial experiences through "Innovation-Challenge Competition". Plans are to create "Women Engineer Day" which will host 15-20 high school girls and to add "Eureka!" program to target middle to high school girls. Understanding physiological and pathological behaviors of live cells in deep tissues can provide both fundamental insights into biological mechanisms and biomedical solutions to diseases. Conventional biosensing technologies, such as optical imaging and planar biochips, are often confined to surface regions. To transcend these limitations, this project aims to develop and validate a novel type of 3D, sensor-innervated, electronic scaffold systems which can enable high-speed and simultaneous measurements of both bioelectrical and biomechanical signals within engineered tissues. The central approach is to employ multi-level hierarchical assemblies to integrate multifunctional biosensors in a programmable 3D scaffold. The developed system will provide a new tool to fundamental studies in cell mechanics and electrophysiology. The research is also expected to lead to translational biochips that can upgrade current single-parameter, planar physiological quantification into multi-parameter, deep-tissue physiological quantifications in engineered tissues.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.