BRITE Fellow: Intelligent Nanoscale 3D Biomanufacturing for Human-on-a-Chip

BRITE 研究员：用于芯片人体的智能纳米级 3D 生物制造

• 批准号: 2135720
• 负责人: Shaochen Chen
• 金额: $ 100万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2135720&HistoricalAwards=false
• 关键词: BRITE; Fellow; Intelligent; Nanoscale; 3D

This Boosting Research Ideas for Transformative and Equitable Advances in Engineering (BRITE) Fellow grant will provide a transformative nanoscale biomanufacturing platform powered by artificial intelligence. At the convergence of advanced additive manufacturing, stem cell biology, biomaterials, and biomechanics, biomanufacturing has the potential for creating three-dimensional biomimetic tissue constructs that can not only redefine the clinical capabilities of regenerative medicine but also transform the toolsets available for various applications such as disease modeling, pre-clinical drug screening, space exploratory and deep ocean studies with human-like tissues, and environmental health and safety studies using engineered human tissues. However, current biomanufacturing technologies have critical bottlenecks: a) they lack the resolution to resolve single cells and are too slow for fabricating a functional three-dimensional human tissues and organs, b) they are often conducted by trial and error, resulting in wasting expensive cells, biomaterials, and time, and c) the lack of systemic interactions with other tissues or organs at the human systemic level. This project aims to address fundamental research issues related to these bottlenecks. On the education side, a comprehensive equity, diversity, and inclusion plan will be developed. Graduate student researchers, undergraduate interns, and K-12 students from diverse backgrounds will have the opportunity to participate in this exciting research project and other outreach programs. As an eminent leader, the principal investigator is poised to make long lasting societal, educational, and commercial impacts on advanced manufacturing and nanoengineering. The research objectives of the project are to investigate ultrafast, near-field optics for nanoscale control of photo-polymerization in three-dimensional bioprinting, to investigate the machine learning methods for three-dimensional bioprinting, and to study the biomechanics and tissue functions of the bioprinted human-on-a-chip. To achieve these objectives, both theoretical and experimental investigations will be carried out to understand the nanoscale light control for bioprinting. Machine learning methods will be investigated for optimal control of the three-dimensional bioprinting process. The biomechanics issues and tissue functions in the human-on-a-chip will be studied. This will be the first attempt in the field to explore ultrafast near-field optics for bioprinting with nanoscale resolution. This research on machine learning methods is also quite novel, particularly for bioprinting so that traditional trial and error optimization will no longer be needed. Furthermore, the human-on-a-chip integrating major tissues such as heart, liver, lung, kidney in the microfluidic system will be an enabling platform for various applications. By integrating the emerging disruptive technologies in the multidisciplinary domains of biomanufacturing, artificial intelligence, and nanophotonics, this research supports exceptionally innovative, high risk, original, and unconventional research projects that have the potential to create new paradigms in advanced manufacturing.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.

这个促进工程变革和公平进步的研究思路（BRITE）研究员赠款将提供一个由人工智能驱动的变革性纳米级生物制造平台。在先进的增材制造，干细胞生物学，生物材料和生物力学的融合中，生物制造具有创造三维仿生组织结构的潜力，不仅可以重新定义再生医学的临床能力，而且还可以改变各种应用的工具集，如疾病建模，临床前药物筛选，空间探索和深海研究与人类相似的组织，以及使用工程化人体组织进行环境健康和安全研究。然而，目前的生物制造技术具有关键的瓶颈：a）它们缺乏分辨单个细胞的分辨率，并且对于制造功能性三维人体组织和器官来说太慢，B）它们通常通过试错进行，导致浪费昂贵的细胞、生物材料和时间，以及c）在人体系统水平上缺乏与其他组织或器官的系统相互作用。该项目旨在解决与这些瓶颈有关的基础研究问题。在教育方面，将制定一项全面的公平、多样性和包容性计划。来自不同背景的研究生研究人员，本科实习生和K-12学生将有机会参加这个令人兴奋的研究项目和其他推广计划。作为一位杰出的领导者，首席研究员准备对先进制造和纳米工程产生长期的社会，教育和商业影响。该项目的研究目标是研究用于三维生物打印中光聚合的纳米级控制的超快近场光学，研究三维生物打印的机器学习方法，并研究生物打印人芯片的生物力学和组织功能。为了实现这些目标，将进行理论和实验研究，以了解生物打印的纳米级光控制。机器学习方法将被研究用于三维生物打印过程的最佳控制。将研究人体芯片的生物力学问题和组织功能。这将是该领域首次尝试探索用于纳米级分辨率生物打印的超快近场光学。这项关于机器学习方法的研究也相当新颖，特别是对于生物打印，因此不再需要传统的试错优化。此外，在微流控系统中集成主要组织如心、肝、肺、肾等的芯片上的人将成为各种应用的使能平台。通过整合生物制造，人工智能和纳米光子学多学科领域的新兴颠覆性技术，这项研究支持非常创新，高风险，原创，该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准。

项目成果

High cell density and high-resolution 3D bioprinting for fabricating vascularized tissues.

• DOI: 10.1126/sciadv.ade7923
• 发表时间: 2023-02-22
• 期刊: SCIENCE ADVANCES
• 影响因子: 13.6
• 作者: You, Shangting;Xiang, Yi;Hwang, Henry H.;Berry, David B.;Kiratitanaporn, Wisarut;Guan, Jiaao;Yao, Emmie;Tang, Min;Zhong, Zheng;Ma, Xinyue;Wangpraseurt, Daniel;Sun, Yazhi;Lu, Ting-yu;Chen, Shaochen
• 通讯作者: Chen, Shaochen

Multimodal Three-Dimensional Printing for Micro-Modulation of Scaffold Stiffness Through Machine Learning

• DOI: 10.1089/ten.tea.2023.0193
• 发表时间: 2023-10-26
• 期刊: TISSUE ENGINEERING PART A
• 影响因子: 4.1
• 作者: Kiratitanaporn，Wisarut;Guan，Jiaao;Chen，Shaochen
• 通讯作者: Chen，Shaochen

Evaluation of CuO nanoparticle toxicity on 3D bioprinted human iPSC-derived cardiac tissues

CuO 纳米颗粒对 3D 生物打印的人 iPSC 衍生心脏组织的毒性评估

• DOI: 10.1016/j.bprint.2023.e00284
• 发表时间: 2023
• 期刊: Bioprinting
• 作者: Miller, Kathleen L.;Sit, Izaac;Xiang, Yi;Wu, Jerry;Pustelnik, Jacob;Tang, Min;Kiratitanaporn, Wisarut;Grassian, Vicki;Chen, Shaochen
• 通讯作者: Chen, Shaochen

3D bioprinting of gene delivery scaffolds with controlled release

• DOI: 10.1016/j.bprint.2023.e00270
• 发表时间: 2023-06-01
• 期刊: Bioprinting
• 作者: Xiang, Yi;Zhong, Zheng;Chen, Shaochen
• 通讯作者: Chen, Shaochen

Light-based vat-polymerization bioprinting

• DOI: 10.1038/s43586-023-00231-0
• 发表时间: 2023-06-22
• 期刊: NATURE REVIEWS METHODS PRIMERS
• 作者: Levato, Riccardo;Dudaryeva, Oksana;Zhang, Yu Shrike
• 通讯作者: Zhang, Yu Shrike