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.

心脏毒性是药物毒性的一个主要部分，因此对于用于非心血管药物的药物的心血管安全性存在相当大的担忧。传统的药物筛选方法，例如使用二维细胞培养和动物模型，具有明显的局限性。需要一些方法来制造心脏组织模型，以更可靠地再现人类生理学的结构和功能。对于心脏毒性测定，监测模型组织对药物的反应同样重要，最好以无标记和非侵入性的方式进行。该研究项目的目标是开发用于心脏毒性筛查的工程心脏组织模型，以促进药物筛选和个性化医疗。 3维模型的设计涉及嵌入柔软且可拉伸的微电子器件的心脏组织，可以连续测量组织内的心脏毒性。该项目的成果可以通过准确预测人类对候选药物的反应，从而显着降低药物开发成本。该研究还有助于减少使用动物模型进行药物筛选。该项目将为 K-12 学生（尤其是来自弱势群体的学生）提供促进 STEM 教育的机会，并向公众传播科学和工程知识。该研究项目旨在开发一种多材料、立体光刻生物打印心脏组织具有嵌入式柔软且可拉伸微电子器件的模型。主要研究思想是，机械匹配的软微电子学和生物打印心脏模型的无缝集成将允许实时连续、原位和组织内测量心脏毒性并响应药物化合物。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。具体步骤包括 1) 优化工程微血管化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、制造和测试软性可拉伸微电子学，3) 集成软性微电子学与生物打印的心脏组织形成杂交心脏组织模型，以及4）研究通过组织内微电子诱导电生理和机械跳动信号筛选一组药物。该奖项反映了 NSF 的法定使命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，并被认为值得支持。

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

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

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