Whole-organ bioreactor with integrated nondestructive 3D molecular imaging

摘要 意义：供体组织短缺仍然是肺移植中的一个关键问题。近期 组织工程学的进步使制造生物工程成为可能。 来自脱细胞器官支架的肺。这些支架是由捐赠者的组织制成的， 在用患者自己的细胞进行再细胞化后变得功能化。然而，翻译的 全肺Decell/Recell技术的临床应用一直受到缺乏尖端技术的阻碍 组织生长技术(如生物反应器)，能够提供精确的反馈和 支架内微环境的控制。创新：所有人都有的一个特定特征 生物反应器目前缺乏的是一种非侵入性地成像它们内部发育中的器官的方法，或者 定量评估细胞随时间的播种和生长情况。目前，这些参数可以 只能通过组织学或基本的输入/输出分析进行破坏性评估 空间敏感度。因此，我们提出了一种新型的生物反应器，它将提供一层新的 基于3D对比增强超声/光声向用户提供信息和反馈 (USPA)图像数据。USPA是一种新的功能成像方式，它利用光源来 在整个组织体积中产生超声波。这种方法可以提供非侵入性 细胞分布和细胞代谢的3D高分辨率图像。参赛队伍：SonoVol， 公司，一家专门从事3D机器人超声成像的公司，将与一个组织团队合作 工程师(UMN)、光声学(Johns Hopkins)和医学图像分析(Kitware)专家 构建一种具有集成无创分子成像反馈的专用生物反应器。 假设：启用USPA的生物反应器将通过以下方式改善整个器官工程研究 提供细胞分布和新陈代谢的实时定量反馈。这将是 与传统组织学相比，加速实验反馈循环，以及 降低成本。方法：在第一阶段，我们将在小鼠肺内证明其可行性。 在第二阶段，我们将扩大该系统的规模，用于翻译大小的猪器官，以及 进行必要的商业研发，将我们的第一批经过校准和验证的系统交付给 顾客。影响：这项技术将是第一个商业化的此类生物反应器， 专门为非侵入性分子成像和非破坏性评估而设计 3D器官构造。最初，它的商业影响将主要集中在学术上 然而，随着肺生物工程技术的成熟，研究机构将该技术 在生物工程肺获得批准后，最终可能在生物技术领域发挥关键作用 临床应用。

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.