3D bionic network as a closed-loop interface for bidirectional communication with cells and tissues

在生物医学系统中实现实时优化可以彻底改变当今现有的医疗技术，使医学更加个性化，治疗更加精确。特别地，这种实时优化有希望实现对中风、心血管疾病、神经障碍等的先进主动治疗，具有增强的功效、降低的风险/毒性和长期的持续效果。生物电子学的最新进展实现了类似组织的力学和小型化架构，以形成与皮肤或内部器官的亲密界面，用于增强生物传感;然而，生物-非生物界面处的单向通信路径限制了设备的适应性和时间动态优化。巨大的挑战仍然是在一个亲密的电子接口的发展，以双向沟通与生物生命系统在多尺度和良性的方式。该提案旨在研究生物-非生物界面的物理和生物通信，并了解使多材料系统异质整合与细胞和组织双向通信的基本机制。这些拟议的项目将使人们能够系统地了解集成方案、结构设计、材料力学、电子制造和接口兼容性，从而通过智能传感和动态优化来推进个性化医疗保健。拟议的研究途径将导致设计和开发一个3D仿生网络作为通信门户，以加深我们对大脑发育和疾病病理学的理解，并为医学提供非传统的智能。在3D结构设计和功能材料的混合构建方面的创新努力将为创造有利于细胞的通信模式奠定工程基础，这将为生物学和临床医学的基础研究开辟新的机会。与危重疾病相关的代谢和生理变化的实时知识对于提供靶向、及时和有效的治疗至关重要。感测组织力学、pH和电生理学的局部变化可以用作反馈基础，以动态地优化药物递送时间表、外科手术干预程序和恢复/康复方案。然而，现有的生物医学系统通常在空间上和时间上将感测与刺激/治疗分离，从而导致对不良事件的出现的延迟响应、错过治疗干预的机会以及副作用的潜在风险。该提案旨在开发和设计一种仿生电子网络，该网络依赖于生物启发的设计方法，以实现闭环通信的细胞偏好模式，目标是模糊生物-非生物界面的障碍，并确保通信的稳定性，灵敏度和准确性。开发一种在微尺度上集成生物传感和刺激的多模态平台，具有高性能和强大的操作特性，可以形成闭环接口网络，从而实现与生物对应物的整体集成和通信。仿生电子网络可以被配置为具有增强的生物相容性和先进的感测能力（包括生物流体压力、微环境温度、电生理学、组织变形等）的电子植入物。设想的系统旨在以自然和无干扰的方式协调传感和刺激，以潜在地加深对伤口愈合的理解，监测心血管生理学，调节细胞代谢，并最终创新主动治疗。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

Enabling real-time optimization in biomedical systems could revolutionize the existing medical technology today, allowing medicine to be more personalized and therapeutics to be more precise. Particularly, such real-time optimization is promising to enable advanced proactive treatment for stroke, cardiovascular diseases, neurological disorders, and others, with enhanced efficacy, reduced risks/toxicity, and sustaining effects over a long period. Recent advancements in bioelectronics achieved the tissue-like mechanics and miniaturized architectures to form an intimate interface with skin or internal organs, for enhanced biosensing; However, the unidirectional pathway of communications at the biotic-abiotic interface limits the device adaptability and time-dynamic optimization. Grand challenges remain in the development of an intimate electronic interface to communicate bidirectionally with biological living systems at multiscale and in a benign fashion. This proposal aims to study physical and biological communications at the biotic-abiotic interface and understand fundamental mechanisms that enable heterogeneous integration of multi-materials systems for bidirectional communications with cells and tissues. These proposed projects will enable a systematic understanding of the integration schemes, structural designs, materials mechanics, electronics fabrication, and interfacing compatibility to advance personalized healthcare with smart sensing and dynamic optimization. The proposed research pathway will lead to the design and develop a 3D bionic network as a communication portal to deepen our understanding of brain development and disease pathology, and to equip medicine with unconventional intelligence. The innovative efforts in 3D structural design and hybrid construction of functional materials will form an engineering foundation for creating cell-favored modalities of communications, which will open up new opportunities in both fundamental research in biology and clinical medicine.Real-time knowledge of metabolic and physiological variations associated with critical diseases is essential in providing target-specific, timely, and effective therapeutic treatments. Sensing local changes in tissue mechanics, pH, and electrophysiology can serve as the feedback basis to optimize, dynamically, pharmacological delivery schedules, surgical intervention procedures, and recovery/rehabilitation protocols. However, existing biomedical systems often separate sensing from stimulation/treatment both spatially and temporally, thus leading to a delayed response to emergence of adverse events, missed opportunities for therapeutic interventions, and potential risks of side effects. This proposal aims to develop and design a bionic electronic network that relies on bio-inspired design approaches to enable cell-favored modalities of closed-loop communications with the goal to blur the barrier at the biotic-abiotic interface and ensure communication stability, sensitivity, and accuracy. Developing a multi-modality platform that integrates biosensing and stimulation at microscale, with high performance and robust operational characteristics can form a closed-loop interfacing network that enables holistic integration and communications with the biological counterpart. The bionic electronic network could be configured as an electronic implant with enhanced biocompatibility and advanced sensing capabilities, including biofluidic pressure, microenvironment temperature, electrophysiology, tissue deformation, and others. The envisioned systems aim to orchestrate sensing and stimulation in a natural and undisruptive fashion to potentially deepen the understanding of wound healing, monitor cardiovascular physiology, modulate the cellular metabolism, and eventually innovate proactive treatment.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.