Collaborative Research: Mimicking Stress-Mediated Invasive Solid Tumor Using Bioprinted Microtissue and Acoustofluidics

合作研究：利用生物打印微组织和声流控技术模拟压力介导的侵袭性实体瘤

• 批准号: 2243507
• 负责人: Chen Shen
• 金额: $ 18.9万
• 依托单位: Rowan University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2243507&HistoricalAwards=false
• 关键词: Collaborative; Research; Mimicking; Stress; Mediated

In solid tumors, chemical and physical signals lead to cancer cells invading nearby tissue and vascularized systems. A well-known physical signal is the interstitial fluid pressure in the tumor region, and existing tumor models have difficulties regulating such a volumetric pressure. It is known that tumor regions with high interstitial pressure typically resist the delivery of the anti-cancer drugs and therapeutics. The goal of this project is to create and study how interstitial pressure can regulate the tumor cell response in a biomimetic (biology mimicking) tumor model. Bioprinting technology and hydrogel engineering will be used to construct the model. The tumor microenvironment will be introduced using the controlled formation of cell spheroids. Physical forces will be induced by acoustic waves, and their role in drug mass transport and the metastatic behavior of tumor cells will be studied. Successful development of such a model will represent a paradigm shift in the cancer community by improving patients’ quality of life, potentially prolonging survival, and opening up new clinical trials to test various new drug formulations. The educational objective is to broaden the participation of underrepresented minorities in STEM fields. This will be accomplished through various educational activities by integrating the research into project-based educational activities for undergraduate students and summer internships for underrepresented students. The tumor microenvironment (TME) is highly complex, with a distinct extracellular matrix composition and leaky vasculature that regulate the tumorigenic function of tumor cells. The investigators hypothesize that acoustic-driven, flow-induced pressure, hydrogel bioprinting, and theoretical simulation could be employed to replicate TME-associated pressure gradients and hypoxic conditions for an invasion behavior in tumor cells. A novel way is proposed for regulating biophysical pressure using the acoustic field in cell-laden microtissue models. A tumor-spheroid-laden microfluidic device equipped with interdigital transducers that generate surface acoustic waves will be developed and used to test the hypothesis. Through digital light processing bioprinting, the project aims to create a high-resolution vascular microtissue with spatial gradients of stiffness and pore sizes. Then, a wide range of acoustic fields (in the megahertz regime) will be made to induce pressure fields onto the tumor spheroids and characterize the tumor cells' invasion markers. Finally, a multi-physics theoretical and numerical approach will be developed to help quantify the variation of acoustic radiation forces within a fluid-saturated poroelastic environment and estimate the induced pressure field.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.

在实体瘤中，化学和物理信号导致癌细胞侵入附近的组织和血管系统，众所周知的物理信号是肿瘤区域中的间质流体压力，并且已知现有的肿瘤模型难以调节这种体积压力。具有高间质压力的肿瘤区域通常会抵抗抗癌药物和治疗的输送，该项目的目标是创建和研究间质压力如何在仿生（生物模拟）中调节肿瘤细胞反应。肿瘤模型将使用生物打印技术和水凝胶工程来构建肿瘤微环境，通过声波诱导物理力的形成，以及它们在药物质量运输和转移行为中的作用。研究肿瘤细胞的成功开发将代表癌症界的范式转变，改善患者的生活质量，可能延长生存期，并开展新的临床试验来测试各种新药物制剂。就是要扩大参与范围这将通过各种教育活动，将已完成的研究整合到针对本科生的基于项目的教育活动和针对代表性不足的学生的暑期实习中。肿瘤微环境（TME）非常复杂，具有独特的细胞外基质组成。研究人员认为，声驱动、流动诱导压力、水凝胶生物打印和理论模拟可用于复制 TME 相关的压力梯度和缺氧条件。提出了一种利用充满细胞的微组织模型中的声场调节生物物理压力的新方法，将开发和使用配备有叉指换能器的充满肿瘤球体的微流体装置。为了验证这一假设，该项目旨在通过数字光处理生物打印来创建具有刚度和孔径空间梯度的高分辨率血管微组织，然后产生广泛的声场（兆赫兹级）。最后，将开发一种多物理理论和数值方法来帮助量化流体饱和多孔弹性体中声辐射力的变化。该奖项反映了 NSF 的法定使命，并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，被认为值得支持。

项目成果

Underwater double vortex generation using 3D printed acoustic lens and field multiplexing

使用 3D 打印声学透镜和场复用产生水下双涡流

• DOI: 10.1063/5.0201781
• 发表时间: 2024-03
• 期刊: APL Materials
• 影响因子: 6.1
• 作者: Ellouzi, Chadi;Zabihi, Ali;Aghdasi, Farhood;Kayes, Aidan;Rivera, Milton;Zhong, Jiaxin;Miri, Amir;Shen, Chen
• 通讯作者: Shen, Chen

Experimental demonstration of rainbow trapping of elastic waves in two-dimensional axisymmetric phononic crystal plates

二维轴对称声子晶体板中弹性波彩虹捕获的实验演示

• DOI: 10.1121/10.0025179
• 发表时间: 2024-03
• 期刊: The Journal of the Acoustical Society of America
• 作者: Ellouzi, Chadi;Zabihi, Ali;Gormley, Louis;Aghdasi, Farhood;Stojanoska, Katerina;Miri, Amir;Jha, Ratneshwar;Shen, Chen
• 通讯作者: Shen, Chen