Nondestructive, High Resolution Imaging Platform For Tissue Regeneration Research

用于组织再生研究的无损高分辨率成像平台

• 批准号: 8744688
• 负责人: SHAY SOKER
• 金额: $ 18.62万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8744688
• 关键词: Achievement; Address; Area; Ballistics; Biological; Biological Assay; Biological Process; Biology; Biomedical Engineering; Bioreactors; Blood Vessels; Blood capillaries; Cancer Biology; Cell Communication; Cell Culture Techniques; Cell Differentiation process; Cell physiology; Cells; Coculture Techniques; Complex; Computational Technique; Confocal Microscopy; Data; Development; Developmental Biology; Disease; Disease model; Documentation; Endothelial Cells; Extracellular Matrix; Fiber; Fiber Optics; Fluorescent Probes; Functional disorder; Future; Generations; Goals; Histocompatibility Testing; Histology; Human; Image; Imagery; Imaging Device; Imaging technology; In Vitro; Label; Light; Manuscripts; Medical Research; Methods; Microscopy; Modeling; Molecular; Monitor; Motivation; Muscle; Muscle Fibers; Natural regeneration; Optics; Organism; Pathogenesis; Pathology; Penetration; Pharmaceutical Preparations; Photons; Physiology; Play; Process; Publishing; Research; Resolution; Role; Sampling; Seminal; Skeletal Muscle; Solutions; Stem cells; Structure; System; Techniques; Technology; Testing; Time; Tissue Engineering; Tissue Model; Tissues; United States National Institutes of Health; Validation; absorption; base; capillary; cell type; clinically relevant; fluorescence imaging; high throughput screening; image reconstruction; imaging modality; improved; in vivo; injured; instrument; interdisciplinary approach; minimally invasive; molecular imaging; new technology; novel; optical fiber; optical imaging; public health relevance; research and development; scaffold; tissue culture; tissue regeneration; tomography

DESCRIPTION (provided by applicant): Tissue development and regeneration is highly complex and dynamic, involved with extensive remodeling of cells and the extracellular matrix surrounding them inside the developing and/or injured tissues. Despite the rapid development of tissue engineering technologies to study regeneration, a major barrier still exists in our inabilit to monitor dynamic biological processes in a minimally invasive real-time fashion, which significantly reduces the clinical relevance of these techniques. Most available assessment methods are static, requiring sacrifice of experimental samples at fixed time points. Therefore, there is an unmet need for new technologies that will provide non-destructive and dynamic monitoring of the development and regeneration processes. Optical imaging in biology can be broadly classified as either ballistic imaging or diffusive imaging. The combination of fluorescent and bioluminescent probes with optoelectronics and computing techniques has led to the development of optical molecular imaging tools that allow the visualization of biologic interactions in complex, living systems over time. However, despite the great potential of optical molecular imaging, it has not yet been harnessed as an enabling technology for tissue regeneration research, due to tissue turbidity, resulting in strong scatter and absorption of light and limited penetration depth, requiring direct view of the tissue. We have recently published several seminal manuscripts describing the development of an indirect, non-destructive, cellular-level imaging instrument through a combination of fiber optic technology and an image reconstruction approach and generation of bioengineered mature and vascularized skeletal muscle tissue using combinations of fluorescently labeled cells. These achievements serve as the motivation for the current proposal, which aims to utilize the model of bioengineered skeletal muscle to develop and validate a novel optical molecular tomography platform, which could be broadly used for tissue regeneration research. We hypothesize that 1) optical imaging, photon transport modeling, and image reconstruction will allow for the non- invasive (indirect), dynamic analysis of bioengineered muscle tissue constructs~ and 2) tomography of distinct fluorescent probes will improve the examination of developing bioengineered muscle constructs, comprised of multiple cell types. We will test these hypotheses by developing a multiwell tissue culture dish equipped with fiber-based imaging system. We will first test the capacity of the imaging system to generate optical phantoms of fluorescently labeled cells and subsequently use the imaging system to assess the organization and differentiation of muscle progenitor and endothelial cells into a multicellular skeletal muscle tissue in vitro. These studies have the potential to drive a paradigm shift from static assays of cellular function in 2D culture models towards systematic analyses of 3D tissues. Achieving the goals set forth in this proposal will establish a novel technology to construct and image 3D composite bioengineered tissues and improve our understanding of tissue development and regeneration mechanisms.

描述（由申请人提供）：组织发育和再生是高度复杂和动态的，涉及发育和/或受损组织内细胞和细胞外基质周围的广泛重塑。尽管组织工程技术的快速发展，研究再生，一个主要的障碍仍然存在于我们无法监测动态的生物过程中的微创实时的方式，这显着降低了这些技术的临床相关性。大多数可用的评估方法是静态的，需要在固定的时间点牺牲实验样品。因此，对于将提供开发和再生过程的非破坏性和动态监测的新技术存在未满足的需求。 生物学中的光学成像可以大致分为弹道成像或扩散成像。结合荧光 生物发光探针与光电子学和计算技术的结合导致了光学分子成像工具的发展，该工具允许随着时间的推移可视化复杂的生命系统中的生物相互作用。然而，尽管光学分子成像具有巨大的潜力，但由于组织混浊，导致光的强散射和吸收以及有限的穿透深度，需要直接观察组织，因此尚未将其用作组织再生研究的使能技术。我们最近发表了几篇开创性的手稿，描述了一种间接的，非破坏性的，细胞水平的成像仪器的发展，通过光纤技术和图像重建方法的组合，并产生生物工程的成熟和血管化的骨骼肌组织使用荧光标记的细胞的组合。这些成果是当前提案的动机，其目的是利用生物工程骨骼肌模型开发和验证一种新的光学分子断层扫描平台，该平台可广泛用于组织再生研究。我们假设1）光学成像、光子传输建模和图像重建将允许生物工程化肌肉组织构建体的非侵入性（间接）动态分析，以及2）不同荧光探针的断层扫描将改善对由多种细胞类型组成的开发中的生物工程化肌肉构建体的检查。我们将通过开发一个配备光纤成像系统的多孔组织培养皿来测试这些假设。我们将首先测试成像系统产生荧光标记细胞的光学幻影的能力，随后使用成像系统来评估肌肉祖细胞和内皮细胞在体外向多细胞骨骼肌组织的组织和分化。 这些研究有可能推动从2D培养模型中的细胞功能静态测定向3D组织的系统分析的范式转变。实现本提案中提出的目标将建立一种新的技术来构建和成像3D复合生物工程组织，并提高我们对组织发育和再生机制的理解。

项目成果

Adaptive mode control based on a fiber Bragg grating.

基于光纤布拉格光栅的自适应模式控制。

• DOI: 10.1364/ol.40.003488
• 发表时间: 2015
• 期刊: Optics letters
• 影响因子: 3.6
• 作者: Lu,Peng;Wang,Anbo;Soker,Shay;Xu,Yong
• 通讯作者: Xu,Yong

The role of endothelial cells in myofiber differentiation and the vascularization and innervation of bioengineered muscle tissue in vivo.

• DOI: 10.1016/j.biomaterials.2012.09.045
• 发表时间: 2013-01
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Criswell, Tracy L.;Corona, Benjamin T.;Wang, Zhan;Zhou, Yu;Niu, Guoguang;Xu, Yong;Christ, George J.;Soker, Shay
• 通讯作者: Soker, Shay