CAREER: Hybrid Biorobotic Matrices to Simulate Diaphragmatic and Myocardial Biomechanics

职业：混合生物机器人矩阵模拟膈肌和心肌生物力学

• 批准号: 1847541
• 负责人: Ellen Roche
• 金额: $ 53.68万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1847541&HistoricalAwards=false
• 关键词: CAREER; Hybrid; Biorobotic; Matrices; Simulate

In order to improve understanding of an organ system, researchers often build physical/benchtop models that mimic the system sufficiently to reproduce, observe, and measure functions that are challenging to evaluate in the body. Though many such models of the cardiovascular and respiratory systems have been developed to simulate the motions of the beating heart and breathing, none faithfully replicates the mechanics of the diaphragm or faithfully mimics the three-dimensional twisting and compressive motion of the heart. Thus, the overall goal of this project is to build a lifelike, benchtop model that recreates the motion and function of the heart and the diaphragm using a combination of advanced robotic techniques and actual organic tissue. This model will provide insights into physiology, pathology and interdependence of the systems and serve as an innovative and effective teaching tool for educating students on cardiovascular and respiratory physiology and pathology. It will also serve as an anatomically and physiologically accurate testbed for implantable cardiac devices, representing a vast improvement over existing models and ultimately reducing the requirement for testing devices in animal models. Finally, it will act as an impactful visualization tool for educating and engaging the broader community (for example in museums and in Children's hospitals). The PI will use this demonstration and teaching model as one of many approaches in a multi-pronged initiative to recruit, train and retain a new generation of women in academic scientific positions.The goal of this project is to shift the paradigm of benchtop simulators from one where the respiratory and cardiovascular systems are independently simulated with synthetic phantoms or ex vivo tissue and motion is passively driven by fluid or external components to one where functional dynamic tissue is recreated using programmable biomimetic soft active materials. Synthetic soft robotic muscular simulators for the diaphragm and heart muscle (myocardium) will be combined with ex vivo biological tissue (entire lungs and intracardiac structures respectively) to create "hybrid biorobots" that will enable accurate representation of lung and heart motion, while preserving key anatomical structures, thus maintaining form while recapitulating function. Clinically derived motion data of the diaphragm and heart will be used to develop algorithms to "program" the design of fiber reinforced biomimetic soft actuators. Subsequently, these active elements will be embedded in anthropomorphic matrices to mimic the form and function of the diaphragm and heart. Diaphragm-driven breathing mechanics and cardiovascular hemodynamics will be recreated using pressurized anatomical chambers and mock circulatory loops. The Research Plan is organized under three objectives. The FIRST OBJECTIVE is to create a modular, active biorobotic diaphragm that can be integrated into an in vitro testbed that can be used simulate physiological and pathological biomechanics and generate ex vivo lung ventilation. The in vitro testbed will integrate pressurized chambers separated by an interchangeable diaphragm mimic to replicate the physiologic pressures of the thoracic and abdominal cavities. Soft-robotic actuators will be programmed to mimic the desired diaphragm motion trajectory as computationally extracted from clinical MRI data. This will be the first functional soft robotic diaphragm mimic to replicate a variety of clinically derived diaphragm motions. The SECOND OBJECTIVE is to create a cardiovascular testbed including a biorobotic heart that recreates cardiac wall motion and generates pressure changes to simulate hemodynamic conditions. A novel hybrid fabrication process will be used to preserve the intracardiac structures (endothelial lining, septum, valves, papillary muscles and chordae tendinae) of the heart using ex vivo tissue (porcine hearts) or high-resolution 3D printing. The active heart muscle will be replaced with a synthetic soft material containing fiber-reinforced actuators oriented in desired configurations. The biorobotic heart will be integrated with a partially compliant vascular flow loop to simulate hemodynamics. This will be the first realization of a soft biorobotic heart that integrates organic intracardiac tissue with soft robotic myocardium and the first cardiac simulator where cardiovascular hemodynamics are driven completely by a myocardial substitute that is capable of replicating twist as well as compression, which is critically important in the performance assessment of medical implants. The THIRD OBJECTIVE is to integrate components to make a cardiorespiratory platform and to demonstrate its utility in a model to simulate respiratory and hemodynamic biomechanics of Fontan patients. Physical cavities of the respiratory simulator will be designed based on Fontan patients' CT and MRI data. Based on previous work, a controller that actuates physiological pressure profiles during a breathing cycle in a simulated chest cavity of a Fontan patient with total cavopulmonary bypass will be developed. The respiratory simulator will then be combined with a partially compliant vascular flow loop to simulate venous pressure and flow patterns of Fontan patients. This will be the first combined cardiorespiratory simulator using a soft robotic heart and diaphragm and the first platform to recreate the Fontan physiology including both trans-diaphragmatic pressures and abdominal pressure.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.

为了提高对器官系统的理解，研究人员经常建立物理/台式机模型，这些模型可以充分模仿该系统以复制，观察和测量在体内评估的具有挑战性的功能。尽管已经开发出许多此类心血管和呼吸系统模型来模拟跳动心脏和呼吸的动作，但没有一个忠实地复制隔膜的力学或忠实地模仿心脏的三维扭曲和压缩运动。因此，该项目的总体目标是建立一个栩栩如生的台式模型，该模型使用先进的机器人技术和实际有机组织的组合来重现心脏的运动和功能和隔膜。 该模型将提供有关系统生理，病理学和相互依存关系的见解，并作为一种创新和有效的教学工具，用于教育学生有关心血管和呼吸系统生理和病理学的教育。它还将作为可植入心脏设备的解剖学和生理准确的测试床，代表了对现有模型的巨大改进，并最终降低了动物模型中测试设备的需求。最后，它将充当有影响力的可视化工具，用于教育和吸引更广泛的社区（例如在博物馆和儿童医院中）。 PI将使用这种演示和教学模型作为多方面的倡议中的众多方法之一使用可编程的仿生软活性材料来重新创建功能动态组织。 用于隔膜和心肌（心肌）的合成软机器人肌肉肌肉模拟器将与外体生物组织（分别为整个肺和心内结构）结合使用，以创建“杂交生物体”，从而可以启用肺部和心脏运动的准确代表，同时保留钥匙的钥匙结构，同时恢复钥匙的启用。隔膜和心脏的临床衍生运动数据将用于开发算法，以“编程”纤维增强的仿生软致动器的设计。随后，这些活性元素将嵌入拟人化矩阵中，以模仿隔膜和心脏的形式和功能。通过加压解剖室和模拟循环环将重新创建隔膜驱动的呼吸力学和心血管血液动力学。 研究计划是在三个目标下组织的。 第一个目的是创建一个模块化的活性生物体隔膜，可以将其集成到体外测试床中，可用于模拟生理和病理生物力学并产生离体肺通风。体外测试床将整合被可互换diaphragm模拟的加压室，以复制胸腔和腹腔的生理压力。 将对软动态执行器进行编程，以模仿从临床MRI数据中提取的计算中所需的隔膜运动轨迹。这将是第一个功能性软机器人隔膜模拟物，以复制各种临床衍生的隔膜运动。 第二个目标是创建一个心血管测试床，包括重现心脏壁运动并产生压力变化以模拟血液动力学条件的心血管心脏。一种新型的杂种制造过程将用于保留心脏内衬里（内皮衬里，隔隔，瓣膜，乳头肌肉和脊柱肌tendineee），并使用离体组织（猪心）或高分辨率3D打印。活跃的心肌将被含有所需构型的纤维增强执行器的合成软材料代替。生物生物质心脏将与部分兼容的血管流动环集成，以模拟血液动力学。 这将是一种柔软的生物生物心脏心脏的第一次实现，该心脏将有机心脏内组织与软机器人心肌和第一个心脏模拟器整合在一起，在该心肌血液动力学中完全由心肌替代品完全驱动，而心肌替代品能够复制扭曲和压缩，这对于医疗植入者的绩效评估至关重要。 第三个目标是整合组件以建立心肺平台，并在模型中证明其效用，以模拟Fontan患者的呼吸道和血液动力学生物力学。呼吸模拟器的物理空腔将基于Fontan患者的CT和MRI数据设计。 基于先前的工作，将开发一个在呼吸周期内在呼吸周期中促进生理压力曲线的控制器，将开发出全腔旁路的Fontan患者的模拟胸腔。 然后，呼吸模拟器将与部分兼容的血管流环相结合，以模拟Fontan患者的静脉压力和流动模式。这将是使用柔软的机器人心脏和隔膜的第一个结合心肺模拟器，也是第一个重现Fontan生理学的平台，包括跨二足压力和腹部压力。这奖反映了NSF的法规任务，并认为通过基金会的知识优点和广泛的crietia crietia criter criter criteria criter criter criter criter criter criteria criter criteria criter criteria criteria criter criteria criteria recteria criteria criteria均值得一提。

项目成果

An organosynthetic soft robotic respiratory simulator

• DOI: 10.1063/1.5140760
• 发表时间: 2020-06-01
• 期刊: APL BIOENGINEERING
• 影响因子: 6
• 作者: Horvath, Markus A.;Hu, Lucy;Roche, Ellen T.
• 通讯作者: Roche, Ellen T.

Soft robotic patient-specific hydrodynamic model of aortic stenosis and ventricular remodeling

• DOI: 10.1126/scirobotics.ade2184
• 发表时间: 2023-02-22
• 期刊: SCIENCE ROBOTICS
• 影响因子: 25
• 作者: Rosalia，Luca;Ozturk，Caglar;Roche，Ellen T.
• 通讯作者: Roche，Ellen T.

Computational Design of a Soft Robotic Myocardium for Biomimetic Motion and Function

• DOI: 10.1002/adfm.202206734
• 发表时间: 2022-08
• 期刊: Advanced Functional Materials
• 影响因子: 19
• 作者: Clara Park;C. Ozturk;E. Roche

Precurved, Fiber-Reinforced Actuators Enable Pneumatically Efficient Replication of Complex Biological Motions

预弯曲纤维增强执行器可实现复杂生物运动的气动高效复制

• DOI: 10.1089/soro.2020.0087
• 发表时间: 2021
• 期刊: Soft Robotics
• 影响因子: 7.9
• 作者: Hu, Lucy;Gau, Dominik;Nixon, James;Klein, Melissa;Fan, Yiling;Menary, Gary;Roche, Ellen T.
• 通讯作者: Roche, Ellen T.

High-Fidelity Physical Organ Simulators: From Artificial to Bio-Hybrid Solutions

• DOI: 10.1109/tmrb.2021.3063808
• 发表时间: 2021-05-01
• 期刊: IEEE TRANSACTIONS ON MEDICAL ROBOTICS AND BIONICS
• 作者: Maglio, S.;Park, C.;Roche, E. T.
• 通讯作者: Roche, E. T.