Collaborative Research: Transforming Cardiotoxic Drug Screening Using Bioprinted Myocardial Tissue Model with Self-Sensing Capacity

合作研究：利用具有自我感知能力的生物打印心肌组织模型改变心脏毒性药物筛选

• 批准号: 1936105
• 负责人: Y Shrike Zhang
• 金额: $ 30万
• 依托单位: Brigham & Women's Hospital Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1936105&HistoricalAwards=false
• 关键词: Collaborative; Research; Transforming; Cardiotoxic; Drug

Cardiotoxicity represents a major segment of drug toxicities, so there are considerable concerns about the cardiovascular safety profile of drugs used for non-cardiovascular medication. Conventional drug screening approaches, such as using a 2-dimensional cell culture and animal models, have notable limitations. Approaches are needed to fabricate cardiac tissue models that more reliably reproduce human physiology with respect to their structure and function. For cardiotoxicity assays it is equally important to monitor the behavior of the model tissue in response to drugs, ideally in a label-free and non-invasive manner. The goal of this research project is to develop an engineered cardiac tissue model for cardiotoxicity screening that will facilitate drug screening and personalized medicine. The design of the 3-dimensional model involves cardiac tissues that are embedded with soft and stretchable microelectronics that can continuously measure cardiotoxicity within the tissue. The outcomes of this project could lead to significant cost reductions for drug development by accurately predicting human responses to drug candidates. The research also could help reduce the use of animal models for drug screening. The project will provide opportunities to promote STEM education for K-12 students, especially those from under-represented groups, and to disseminate science and engineering knowledge to the public.This research project aims to develop a multi-material, stereolithographically-bioprinted cardiac tissue model with embedded soft and stretchable microelectronics. The main research idea is that seamless integration of mechanically matched soft microelectronics and bioprinted cardiac models will allow for continuous, in situ and intra-tissue measurements of cardiotoxicity in real time and in response to pharmaceutical compounds. The project participants will conduct experimental and analytical studies to design, optimize, fabricate, characterize and validate the hybridized cardiac tissue model. Specific steps include 1) optimizing the design and fabrication of the engineered microvascularized cardiac tissue model to achieve structural and functional similarity to its in vivo counterpart, 2) designing, analyzing, fabricating, and testing soft, stretchable microelectronics, 3) integrating the soft microelectronics with the bioprinted cardiac tissue to form hybridized cardiac tissue model, and 4) studying the screening of a panel of drugs with induced electrophysiological and mechanical beating signals from the intra-tissue microelectronics.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.

心脏毒性代表了药物毒性的主要部分，因此人们对用于非心血管药物的药物的心血管安全性有很大的关注。常规的药物筛查方法，例如使用二维细胞培养和动物模型，具有明显的局限性。需要采用方法来制造心脏组织模型，从而更可靠地重现人类的结构和功能。对于心脏毒性测定，监测模型组织对药物的行为同样重要，理想情况下，以无标签和非侵入性方式监测模型组织的行为。该研究项目的目的是开发一种工程的心脏组织模型，用于心脏毒性筛查，以促进药物筛查和个性化医学。三维模型的设计涉及心脏组织，这些心脏组织嵌入了柔软且可拉伸的微电子，可以连续测量组织内的心脏毒性。通过准确预测人类对候选药物的反应，该项目的结果可能会导致药物开发的大量成本降低。这项研究还可以帮助减少动物模型进行药物筛查。该项目将为K-12学生（尤其是来自代表性不足的群体的学生）提供机会，并向公众传播科学和工程知识。该研究项目旨在通过嵌入的软且可伸展的微电子电脑开发多材料，立体刻印的心脏组织模型。主要的研究思想是，机械匹配的软性微电子和生物打印心脏模型的无缝整合将使心脏毒性实时的原位和组织内测量值连续，并响应药物化合物。项目参与者将进行实验和分析研究，以设计，优化，制造，表征和验证杂交心脏组织模型。特定步骤包括1）优化工程微血管心脏组织模型的设计和制造，以实现与其体内对应物的结构和功能相似性，2）设计，分析，制造和测试柔软的，可伸展的微型电源，3）与形成杂种型杂种的柔软的微型电动型杂种，并将其整合到杂种中，并与杂种形成杂种型模型，并将其整合在一起。具有诱导电生理学和机械跳动信号的药物来自组织内微电子学。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，被认为值得通过评估来获得支持。

项目成果

Engineering (Bio)Materials through Shrinkage and Expansion.

• DOI: 10.1002/adhm.202100380
• 发表时间: 2021-07
• 期刊: Advanced healthcare materials
• 影响因子: 10
• 作者: Wang M;Li W;Tang G;Garciamendez-Mijares CE;Zhang YS
• 通讯作者: Zhang YS

Photoacoustic imaging of 3D-printed vascular networks.

• DOI: 10.1088/1758-5090/ac49d5
• 发表时间: 2022-01-24
• 期刊: Biofabrication
• 影响因子: 9
• 作者: Ma C;Li W;Li D;Chen M;Wang M;Jiang L;Mille LS;Garciamendez CE;Zhao Z;Zhou Q;Zhang YS;Yao J
• 通讯作者: Yao J

Biosurfactant-Stabilized Micropore-Forming GelMA Inks Enable Improved Usability for 3D Printing Applications

• DOI: 10.1007/s40883-022-00250-5
• 发表时间: 2022-03
• 期刊: Regenerative Engineering and Translational Medicine
• 影响因子: 2.6
• 作者: Xin-Sheng Qin;Mian Wang;Wanlu Li;Y. S. Zhang

A Heart-Breast Cancer-on-a-Chip Platform for Disease Modeling and Monitoring of Cardiotoxicity Induced by Cancer Chemotherapy.

• DOI: 10.1002/smll.202004258
• 发表时间: 2021-04
• 期刊: Small (Weinheim an der Bergstrasse, Germany)
• 作者: Lee J;Mehrotra S;Zare-Eelanjegh E;Rodrigues RO;Akbarinejad A;Ge D;Amato L;Kiaee K;Fang Y;Rosenkranz A;Keung W;Mandal BB;Li RA;Zhang T;Lee H;Dokmeci MR;Zhang YS;Khademhosseini A;Shin SR
• 通讯作者: Shin SR

Micropore‐Forming Gelatin Methacryloyl (GelMA) Bioink Toolbox 2.0: Designable Tunability and Adaptability for 3D Bioprinting Applications

Micropore™ 形成明胶甲基丙烯酰 (GelMA) Bioink Toolbox 2.0：针对 3D 生物打印应用的可设计可调性和适应性

• DOI: 10.1002/smll.202106357
• 发表时间: 2022
• 期刊: Small
• 影响因子: 13.3
• 作者: Yi, Sili;Liu, Qiong;Luo, Zeyu;He, Jacqueline Jialu;Ma, Hui‐Lin;Li, Wanlu;Wang, Di;Zhou, Cuiping;Garciamendez, Carlos Ezio;Hou, Linxi
• 通讯作者: Hou, Linxi