Modeling Perineural Invasion Using a Bioorthogonally Integrated Hydrogel Platform

使用生物正交集成水凝胶平台模拟神经周围侵袭

基本信息

  • 批准号:
    1809612
  • 负责人:
  • 金额:
    $ 54.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-08-15 至 2022-07-31
  • 项目状态:
    已结题

项目摘要

Non Technical Abstract:To accelerate the development of cancer therapies, we need to understand cancer metastasis, a process by which cancer cells detach from the primary tumor site and spread to a different tissue or organ. In addition to blood and lymph systems, cancer cells can hijack the nerves to travel to a distant location. Although nerve-guided tumor dissemination is clinically observed, the underlying mechanism remains largely unknown. The goal of this project is to develop lab-grown tumor models for studying cancer-nerve interactions. Prostate cancer cells will be allowed to aggregate in a custom-designed mold to form compact, micrometer-sized spheres. The multicellular spheres will be embedded in a gelatinous material exhibiting spatial gradients of stiffness, degradability and cell binding capacity. Aligned, micron-sized synthetic fibers capable of releasing molecules that nerve cells produce will be included in the scaffold to mimic the cancer-associated nerve fibers. Using this model, the PIs will investigate how cancer cells grow and travel along the nerve-mimicking fibers. The PIs will determine whether the nerve-guided cell migration can be blocked by compounds that reduce the association of cancer cells with the nerve. These studies will improve understanding of cancer metastasis and accelerate the design of innovative strategies for cancer diagnosis and treatment, thus justifying the public support. Our outreach and education efforts will help maintain the United States' global competitiveness. In addition to course development and student training, effort will be dedicated to the engaging and empowering of pre-service, early childhood teachers who will inspire the next generation scientists.Technical Abstract:This award by the Biomaterials Program in the Division of Materials Research to the University of Delaware (UD) aims to engineer a physiologically relevant tumor model with an integrated cancer-nerve interface to better understand perineural invasion, a process in which malignant cells migrate along, around and through nerves to a distal location. We will accomplish this goal by culturing pre-assembled multicellular tumoroids in a hyaluronic acid-derived hydrogel matrix containing nerve mimicking polymer fibers. The engineered microenvironment will be produced via a novel interfacial crosslinking process employing the rapid, bioorthogonal and highly efficient cycloaddition reaction between s-tetrazines and trans-cyclooctene derivatives. The hydrogel matrix will exhibit defined spatial gradients to promote cell proliferation, aggregation and migration, while the aligned, micron-sized fibers will mimic the tumor-associated nerve fibers structurally and biochemically. We will characterize the phenotype and migration of prostate cancer cells, as well as their responses to pharmacological inhibitors. The goal is to gain improved understanding of the neurotropism of malignant cancer cells, accelerating the design of innovative strategies for cancer diagnosis and treatment. The proposed research activity will not only contribute to the education of the next generation scientists and engineers, but also empower early childhood teachers. Concerted effort will be dedicated to the creation of discovery-based teaching modules, lab-based research modules and community-based design and innovation activities.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.
为了加速癌症治疗的发展,我们需要了解癌症转移,这是癌细胞从原发肿瘤部位分离并扩散到不同组织或器官的过程。除了血液和淋巴系统外,癌细胞还可以劫持神经前往远处。虽然神经引导的肿瘤传播在临床上观察到,基本机制仍然在很大程度上未知。该项目的目标是开发实验室生长的肿瘤模型,用于研究癌症-神经相互作用。前列腺癌细胞将被允许在定制设计的模具中聚集,形成紧凑的微米大小的球体。多细胞球体将嵌入凝胶状材料中,该凝胶状材料表现出刚度、降解性和细胞结合能力的空间梯度。能够释放神经细胞产生的分子的对齐的微米级合成纤维将被包括在支架中,以模拟癌症相关的神经纤维。利用这个模型,PI将研究癌细胞如何沿着神经模拟纤维生长和沿着行进。PI将确定神经引导的细胞迁移是否可以被减少癌细胞与神经关联的化合物阻断。这些研究将提高对癌症转移的认识,并加速癌症诊断和治疗的创新策略的设计,从而证明公众的支持是合理的。我们的推广和教育工作将有助于保持美国的全球竞争力。除了课程开发和学生培训,努力将致力于从事和授权的前服务,幼儿教师谁将激励下一代科学家。技术摘要:该奖项由生物材料计划在材料研究部的特拉华州大学(UD)的目的是设计一个生理相关的肿瘤模型与综合癌症神经接口,以更好地了解神经周围的入侵,在这个过程中,恶性细胞迁移沿着,周围和通过神经到远端位置。我们将通过在含有神经模拟聚合物纤维的透明质酸衍生的水凝胶基质中培养预组装的多细胞类肿瘤来实现这一目标。该工程微环境将通过一种新的界面交联方法产生,该方法采用s-四嗪和反式环辛烯衍生物之间的快速,生物正交和高效的环加成反应。水凝胶基质将表现出限定的空间梯度以促进细胞增殖、聚集和迁移,而对齐的微米级纤维将在结构上和生物化学上模拟肿瘤相关的神经纤维。我们将表征前列腺癌细胞的表型和迁移,以及它们对药物抑制剂的反应。其目标是更好地了解恶性癌细胞的嗜神经性,加速癌症诊断和治疗的创新策略的设计。拟议的研究活动不仅将有助于下一代科学家和工程师的教育,而且还将增强幼儿教师的能力。该奖项反映了NSF的法定使命,并通过使用基金会的知识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

期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Core–Shell Microfibers via Bioorthogonal Layer-by-Layer Assembly
通过生物正交逐层组装的核壳超细纤维
  • DOI:
    10.1021/acsmacrolett.0c00515
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    7.015
  • 作者:
    Ravikrishnan, A.;Zhang, H.;Fox, J. M.;Jia, X.
  • 通讯作者:
    Jia, X.
Hydrogel-Supported, Engineered Model of Vocal Fold Epithelium.
  • DOI:
    10.1021/acsbiomaterials.0c01741
  • 发表时间:
    2021-09-13
  • 期刊:
  • 影响因子:
    5.8
  • 作者:
    Ravikrishnan A;Fowler EW;Stuffer AJ;Jia X
  • 通讯作者:
    Jia X
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Xinqiao Jia其他文献

Tissue Engineering Strategies for Vocal Fold Repair and Regeneration
声带修复和再生的组织工程策略
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    0
  • 作者:
    A. Farran;Zhixiang Tong;R. Witt;Xinqiao Jia
  • 通讯作者:
    Xinqiao Jia
Label-free, in situ monitoring of viscoelastic properties of cellular monolayers via elastohydrodynamic phenomena
通过弹性流体动力学现象对细胞单层的粘弹性特性进行无标记原位监测
  • DOI:
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Tianzheng Guo;X. Zou;Shalini Sundar;Xinqiao Jia;Charles Dhong
  • 通讯作者:
    Charles Dhong
Chemical modification of solid surfaces and interfaces and template-assisted fabrication of surface nanostructures
固体表面和界面的化学改性以及表面纳米结构的模板辅助制造
  • DOI:
  • 发表时间:
    2002
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Xinqiao Jia
  • 通讯作者:
    Xinqiao Jia
Hyaluronic acid-based hydrogels as 3D matrices for in vitro tumor engineering
基于透明质酸的水凝胶作为体外肿瘤工程的 3D 基质
Salivary Gland Tissue Engineering and Repair
唾液腺组织工程与修复
  • DOI:
    10.1016/b978-0-12-397157-9.00050-3
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    7.6
  • 作者:
    S. Pradhan;K. Cannon;D. Zakheim;D. Harrington;R. Duncan;Xinqiao Jia;M. Farach;R. Witt
  • 通讯作者:
    R. Witt

Xinqiao Jia的其他文献

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{{ truncateString('Xinqiao Jia', 18)}}的其他基金

Modeling Salivary Gland Fibrosis Using a Bioorthogonally Integrated Hydrogel Platform
使用生物正交集成水凝胶平台模拟唾液腺纤维化
  • 批准号:
    2243648
  • 财政年份:
    2023
  • 资助金额:
    $ 54.6万
  • 项目类别:
    Standard Grant
Spatial Control of Cell Behavior via Interfacial Bioorthogonal Chemistry
通过界面生物正交化学空间控制细胞行为
  • 批准号:
    1506613
  • 财政年份:
    2015
  • 资助金额:
    $ 54.6万
  • 项目类别:
    Continuing Grant
Travel Support for "Polymeric Biomaterials" Symposium at the 249th American Chemical Society (ACS) National Meeting
第 249 届美国化学会 (ACS) 全国会议“高分子生物材料”研讨会的差旅支持
  • 批准号:
    1464454
  • 财政年份:
    2015
  • 资助金额:
    $ 54.6万
  • 项目类别:
    Standard Grant
Bioactive Scaffolds with Elastomeric Properties for the Engineering of Mechanically Active Tissues
用于机械活性组织工程的具有弹性特性的生物活性支架
  • 批准号:
    1206310
  • 财政年份:
    2012
  • 资助金额:
    $ 54.6万
  • 项目类别:
    Continuing Grant
Travel Support for Students, Post-Docs, and Young Faculty to Attend the Symposium on "Controlling Cellular Behavior with Polymer Synthesis and Engineering" At the 235th ACS Meeting
为学生、博士后和年轻教师参加第 235 届 ACS 会议上的“用聚合物合成和工程控制细胞行为”研讨会提供差旅支持
  • 批准号:
    0801520
  • 财政年份:
    2007
  • 资助金额:
    $ 54.6万
  • 项目类别:
    Standard Grant
CAREER: Mechano-Responsive Biomaterials with Controlled Architectures and Improved Mechanical Properties via Biomimetic Strategies
职业:通过仿生策略具有受控架构和改进机械性能的机械响应生物材料
  • 批准号:
    0643226
  • 财政年份:
    2007
  • 资助金额:
    $ 54.6万
  • 项目类别:
    Standard Grant

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Elucidating cancer-intrinsic mechanisms of perineural invasion in pancreatic cancer
阐明胰腺癌神经周围浸润的癌症内在机制
  • 批准号:
    10647832
  • 财政年份:
    2022
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    $ 54.6万
  • 项目类别:
Elucidation of perineural invasion of distal cholangiocarcinoma using tissue clearing method
使用组织透明法阐明远端胆管癌的神经周围浸润
  • 批准号:
    22K08861
  • 财政年份:
    2022
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    $ 54.6万
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    Grant-in-Aid for Scientific Research (C)
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利用体外共培养模型揭示胰腺癌神经周围浸润的机制
  • 批准号:
    20K22838
  • 财政年份:
    2022
  • 资助金额:
    $ 54.6万
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    Grant-in-Aid for Research Activity Start-up
Elucidating cancer-intrinsic mechanisms of perineural invasion in pancreatic cancer
阐明胰腺癌神经周围浸润的癌症内在机制
  • 批准号:
    10428889
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Investigating the Regulation of RET Receptor-Mediated Perineural Invasion and Metastasis
RET 受体介导的神经周围侵袭和转移的调控研究
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    2021
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  • 财政年份:
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通过显示神经周围侵袭的新小鼠神经胶质瘤模型开发新的治疗方法。
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