Nanosystems Engineering Research Center for Directed Multiscale Assembly of Cellular Metamaterials with Nanoscale Precision: CELL-MET

纳米级精度细胞超材料定向多尺度组装纳米系统工程研究中心：CELL-MET

• 批准号: 1647837
• 负责人: David Bishop
• 金额: $ 1975万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-10-01 至 2027-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1647837&HistoricalAwards=false
• 关键词: Nanosystems; Engineering; Research; Center; Directed

Heart disease is the number one cause of death in the US and a leading cause worldwide, but current medicine cannot regenerate and or repair diseased human heart tissue. Today, there is no cure for a heart attack. The vision of Directed Multiscale Assembly of Cellular Metamaterials with Nanoscale Precision (CELL-MET) Nanosystems Engineering Research Center is to change this. CELL-MET will develop tissue-engineering principles to create scalable, low-cost technologies for growing clinically significant cardiac tissues from cell-level building blocks. The research approach is to adapt and advance novel nanomanufacturing techniques to integrate a variety of functional biological structures and elements into flexible polymer scaffolds that support and guide heart cells. The goal of this project is to create cardiac patches that will someday allow for the repair of hearts damaged by a heart attack or other diseases. In addition to their potential for repairing damaged hearts, artificial cardiac tissues will be used to test the effects of heart drugs or other drugs more realistically and efficiently than is currently possible. Broader impacts will include kindergarten to post-doctoral education and training programs that will produce a diverse, well-trained, world aware workforce to support the new billion dollar industries enabled by CELL-MET research. Industrial partners will work with CELL-MET to create these new industries, developing the business opportunities generated by the research breakthroughs.CELL-MET aims to create functional, clinically significant heart tissue in the laboratory by controlling the cardiac structure across different length scales. At sizes smaller than a micron and up to the ten micron scale of cells, CELL-MET will align heart muscle cells (cardiomyocytes) and connect them to one another via special cellular structures, enabling them to contract and relax in synchrony. At the multicellular scale, it will monitor and control chemical signaling both among these cells and between them and supporting cells. At the scale of tissue constructs, CELL-MET will create highly structured networks of blood vessels lined with epithelial cells, which are needed for any thick tissue. The ten-year vision encompasses the incorporation of endocardial cells that help define the large-scale structure and electrophysiological function of the heart, as well as the valves that ensure unidirectional blood flow.CELL-MET brings together a diverse, world-class team from Boston University, the University of Michigan, Florida International University, Harvard, Columbia, Argonne National Lab, EPFL (Switzerland), and Centro Atomico-Bariloche (Argentina). The team has expertice in semiconductors, photonics, nanotechnology, optical systems, organic molecules, cardiac biology, and cellular assembly. CELL-MET is uniquely positioned to harness the capabilities and synergies among these disciplines. CELL-MET plans to combine novel techniques for patterning molecules on the scale of 50 nm or less with nanometer resolution 3D-printed scaffolds. 3D nanoprinting technologies will produce scaffolds that Atomic Calligraphy and Organic Vapor Jet Printing will write upon to create the focal adhesion points, the places that attach the cells. Advanced tissue engineering techniques will populate these nanostructures with cardiomyocytes and other cardiac cell types to produce the living tissues.As CELL-MET advances the technology, it will work with commercial members of its Innovation Ecosystem to create entirely new industries. Through its Education and Workforce Development programs, CELL-MET will recruit and train a diverse, world aware workforce to support the industries that it creates.

心脏病是美国的头号死因，也是全球的主要死因，但目前的医学无法再生和/或修复患病的人类心脏组织。今天，没有治愈心脏病发作的方法。定向多尺度组装细胞超材料与纳米级精度（CELL-MET）纳米系统工程研究中心的愿景是改变这一点。CELL-MET将开发组织工程原理，以创建可扩展的，低成本的技术，用于从细胞水平构建块中生长临床重要的心脏组织。研究方法是适应和推进新型纳米制造技术，将各种功能生物结构和元素整合到支持和引导心脏细胞的柔性聚合物支架中。该项目的目标是创造心脏补丁，有朝一日可以修复心脏病发作或其他疾病造成的心脏损伤。人工心脏组织除了具有修复受损心脏的潜力外，还将被用于测试心脏药物或其他药物的效果，比目前可能的更真实、更有效。更广泛的影响将包括幼儿园到博士后教育和培训计划，这些计划将产生多样化，训练有素，具有世界意识的劳动力，以支持CELL-MET研究所支持的新的十亿美元产业。产业合作伙伴将与CELL-MET合作创建这些新产业，开发研究突破所产生的商业机会。CELL-MET旨在通过控制不同长度尺度的心脏结构，在实验室中创建功能性的、具有临床意义的心脏组织。在小于一微米和高达十微米尺度的细胞中，CELL-MET将对齐心肌细胞（心肌细胞），并通过特殊的细胞结构将它们彼此连接，使它们能够同步收缩和放松。在多细胞尺度上，它将监测和控制这些细胞之间以及它们与支持细胞之间的化学信号。在组织结构的规模上，CELL-MET将创建由上皮细胞排列的高度结构化的血管网络，这是任何厚组织所需要的。CELL-MET汇集了来自波士顿大学、密歇根大学、佛罗里达国际大学、哈佛大学、哥伦比亚大学、阿贡国家实验室、洛桑联邦理工学院（EPFL）、麻省理工学院（麻省理工学院）、麻省理工（瑞士）和Centro Atomico-Bariloche（阿根廷）。该团队拥有半导体、光子学、纳米技术、光学系统、有机分子、心脏生物学和细胞组装方面的专业知识。CELL-MET在利用这些学科之间的能力和协同作用方面具有独特的优势。CELL-MET计划将联合收割机用于在50 nm或更小的尺度上图案化分子的新技术与纳米分辨率3D打印支架相结合。3D纳米打印技术将产生支架，原子书法和有机蒸汽喷射打印将在其上书写，以创建粘着点，即附着细胞的地方。先进的组织工程技术将在这些纳米结构中植入心肌细胞和其他心脏细胞类型，以产生活组织。随着技术的进步，CELL-MET将与其创新生态系统的商业成员合作，创造全新的产业。通过其教育和劳动力发展计划，CELL-MET将招募和培训多元化的，具有世界意识的劳动力，以支持其创建的行业。

项目成果

In vitro Models of Ischemia-Reperfusion Injury.

• DOI: 10.1007/s40883-018-0056-0
• 发表时间: 2018-09
• 期刊: Regenerative engineering and translational medicine
• 影响因子: 2.6
• 作者: Chen T;Vunjak-Novakovic G
• 通讯作者: Vunjak-Novakovic G

Building a Casimir Metrology Platform with a commercial MEMS sensor

使用商用 MEMS 传感器构建卡西米尔计量平台

• DOI: 10.1038/s41378-019-0054-5
• 发表时间: 2019
• 期刊: 07 Nature
• 作者: Stange, A.;Imboden, M.;Javor, J.;Barrett, L.;Bishop, D.
• 通讯作者: Bishop, D.

Simultaneous mapping of nanoscale topography and surface potential of charged surfaces by scanning ion conductance microscopy

• DOI: 10.1039/d0nr04555a
• 发表时间: 2020-10-28
• 期刊: NANOSCALE
• 影响因子: 6.7
• 作者: Chen, Feng;Panday, Namuna;He, Jin
• 通讯作者: He, Jin

GATA6 mutations in hiPSCs inform mechanisms for maldevelopment of the heart, pancreas, and diaphragm.

• DOI: 10.7554/elife.53278
• 发表时间: 2020-10-15
• 期刊: eLife
• 影响因子: 7.7
• 作者: Sharma A;Wasson LK;Willcox JA;Morton SU;Gorham JM;DeLaughter DM;Neyazi M;Schmid M;Agarwal R;Jang MY;Toepfer CN;Ward T;Kim Y;Pereira AC;DePalma SR;Tai A;Kim S;Conner D;Bernstein D;Gelb BD;Chung WK;Goldmuntz E;Porter G;Tristani-Firouzi M;Srivastava D;Seidman JG;Seidman CE;Pediatric Cardiac Genomics Consortium
• 通讯作者: Pediatric Cardiac Genomics Consortium

Printable Organic Electronic Materials for Precisely Positioned Cell Attachment

用于精确定位电池附着的可印刷有机电子材料

• DOI: 10.1021/acs.langmuir.0c03319
• 发表时间: 2021
• 期刊: Langmuir
• 影响因子: 3.9
• 作者: Horowitz, Jeffrey A.;Zhong, Xiaoyang;DePalma, Samuel J.;Ward Rashidi, Maria R.;Baker, Brendon M.;Lahann, Joerg;Forrest, Stephen R.
• 通讯作者: Forrest, Stephen R.