Whole-organ bioreactor with integrated nondestructive 3D molecular imaging

具有集成无损 3D 分子成像的全器官生物反应器

• 批准号: 9977285
• 负责人: Tomasz Joseph Czernuszewicz
• 金额: $ 90.69万
• 依托单位: SONOVOL, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-11 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977285
• 关键词: 3-Dimensional; Acoustics; Address; Agreement; Algorithms; Anatomy; Animal Model; Basic Science; Binding; Biological Assay; Biomedical Engineering; Bioreactors; Biotechnology; Cell Culture Techniques; Cells; Clinic; Clinical; Clinical Trials; Communities; Complex; Computer software; Contrast Media; Custom; Data; Development; Devices; Endothelial Cells; Endothelium; Engineering; Ensure; Evaluation; Family suidae; Feedback; Financial Hardship; Functional Imaging; Future; Generations; Goals; Growth; Heart; Histologic; Histology; Human; Image; Image Analysis; Imaging technology; In Vitro; Institution; Light; Lung; Lung Transplantation; Magnetic Resonance Imaging; Maps; Measurement; Medical; Medical Imaging; Metabolism; Methods; Molecular; Multimodal Imaging; Mus; Organ; Organ Size; Organ Transplantation; Output; Pathology; Patients; Performance; Phase; Procedures; Protocols documentation; Quality Control; Regulation; Research; Research Personnel; Resolution; Resources; Robotics; Role; Sampling; Small Business Innovation Research Grant; Source; Sterility; System; Technology; Testing; Three-Dimensional Image; Time; Tissue Donors; Tissue Engineering; Tissues; Trachea; Transducers; Translating; Translations; Ultrasonic Transducer; Ultrasonic wave; Ultrasonography; Vascular Graft; Vascular Patency; base; cell growth; cellular imaging; contrast enhanced; cost; density; design; experimental study; high resolution imaging; human model; human tissue; imaging modality; imaging study; imaging system; implantation; improved; innovation; interest; migration; molecular imaging; nanoparticle; non-invasive imaging; novel; organ growth; photoacoustic imaging; preclinical imaging; research and development; scaffold; scale up; serial imaging; software development; stem cell biology; targeted agent; tool; wasting

Abstract Significance: Donor tissue shortage remains a critical problem in lung transplantation. Recent advances in tissue engineering have allowed for the possibility of generating bioengineered lungs from decellularized organ scaffolds. These scaffolds, created from the donor’s tissue, become functionalized after recellularization with a patient’s own cells. However, translation of whole-lung decell/recell technology to the clinic has been hampered by the lack of sophisticated tissue growth technologies (e.g. bioreactors) that are capable of providing precise feedback and control of the microenvironment within the scaffold. Innovation: One specific feature that all bioreactors currently lack is a way to noninvasively image the developing organs within them, or quantitatively assess the seeding and growth of cells over time. Currently, these parameters can only be evaluated destructively by histology or by rudimentary input/output assays that have no spatial sensitivity. Therefore, we propose a novel bioreactor that will provide a new layer of information and feedback to the user based on 3D contrast-enhanced ultrasound/photoacoustic (USPA) image data. USPA is a new functional imaging modality that utilizes a light source to generate ultrasonic waves throughout a tissue volume. This approach can provide noninvasive high-resolution images of cellular distribution and cellular metabolism in 3D. Team: SonoVol, Inc., a company specializing in 3D robotic ultrasound imaging, will partner with a team of tissue engineer (UMN), photoacoustics (Johns Hopkins), and medical image analysis (Kitware) experts to build a specialized bioreactor with integrated noninvasive molecular imaging feedback. Hypothesis: The USPA enabled bioreactor will improve whole-organ engineering research by providing real time quantitative feedback on cellular distribution and metabolism. This will accelerate the experimental feedback loop as compared to conventional histology, as well as reduce costs. Approach: During Phase I we will demonstrate feasibility within a mouse lung. During Phase II we will scale the system up for use in translational-sized porcine organs, and perform the commercial R&D necessary to deliver our first calibrated and validated systems to customers. Impact: This technology will be the first commercially available bioreactor of its kind, specifically designed for noninvasive molecular imaging and nondestructive assessment of the 3D organ constructs. Initially its commercial impact will be primarily focused at academic research institutions, however as lung bioengineering technologies mature, the technology could eventually serve a critical role in biotech after bioengineered lungs are approved for clinical use.

抽象的 意义：供体组织短缺仍然是肺移植中的关键问题。最近的 组织工程的进步允许产生生物工程的可能性 来自脱细胞器官支架的肺。这些脚手架是由捐助者组织创建的， 用患者自己的细胞进行覆盖后，在功能化。但是，翻译 由于缺乏精致的 组织生长技术（例如生物反应器）能够提供精确反馈和 控制支架内的微环境。创新：全部的一项特定功能 目前缺乏生物反应器是一种无创图像其中的发育器官，或者 随着时间的推移，定量评估细胞的播种和生长。目前，这些参数可以 仅通过组织学或没有具有的基本输入/输出测定对没有的毁灭性评估 空间灵敏度。因此，我们提出了一个新型的生物反应器，该生物反应器将提供新的层 基于3D对比增强超声/光声向用户的信息和反馈 （USPA）图像数据。 USPA是一种新的功能成像方式，它利用光源 在整个组织体积中产生超声波。这种方法可以提供无创的 3D中细胞分布和细胞代谢的高分辨率图像。团队：Sonovol， 一家专门从事3D机器人超声成像的公司将与一组纸巾合作 工程师（UMN），Photosoustics（Johns Hopkins）和医学图像分析（套件）专家 建立具有积分非侵入性分子成像反馈的专业生物反应器。 假设：启用USPA的生物反应器将通过 提供有关细胞分布和代谢的实时定量反馈。这会 与常规组织学相比，加速实验反馈回路 降低成本。方法：在第一阶段，我们将在小鼠肺中证明可行性。 在第二阶段，我们将扩展系统以用于翻译大小的猪器官，以及 执行必要的商业研发，以将我们的第一个校准和经过验证的系统交付给 顾客。影响：该技术将是同类产品中第一个商业上可用的生物反应器 专门设计用于非侵入性分子成像和无损评估 3D器官构造。最初，其商业影响将主要集中在学术上 研究机构，但是随着肺部工程技术的成熟，该技术 在批准生物工程肺后，最终可以在生物技术中发挥关键作用 临床用途。