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。最近 组织工程学的进步使得生物工程 去细胞器官支架的肺。这些支架是由捐赠者的组织制成的， 在用患者自身细胞再细胞化后变得功能化。然而，翻译 全肺decell/recell技术应用于临床一直受到缺乏复杂的 能够提供精确反馈的组织生长技术（例如生物反应器）， 控制支架内的微环境。创新：一个特定的功能，所有 生物反应器目前缺乏的是一种非侵入性成像其中发育器官的方法，或者 定量评估细胞随时间的接种和生长。目前，这些参数可以 仅通过组织学或通过基本的输入/输出测定进行破坏性评价， 空间灵敏度因此，我们提出了一种新的生物反应器，它将提供一个新的层， 基于3D对比度增强超声/光声技术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模式，它利用光源 在整个组织体积中产生超声波。这种方法可以提供非侵入性的 细胞分布和细胞代谢的3D高分辨率图像。团队：Sonopolitan， 股份有限公司、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（约翰霍普金斯）和医学图像分析（Kitware）专家 来建造一个专门的生物反应器，并集成了非侵入性分子成像反馈。 假设：USPA使能的生物反应器将通过以下方式改善全器官工程研究： 提供关于细胞分布和代谢的真实的实时定量反馈。这将 与传统组织学相比，加速实验反馈回路，以及 降低成本方法：在第一阶段，我们将证明在小鼠肺内的可行性。 在第二阶段，我们将扩大该系统的规模，用于实验性大小的猪器官， 进行必要的商业研发，以提供我们第一个经过校准和验证的系统， 客户影响：这项技术将是同类中第一个商业化的生物反应器， 专门设计用于非侵入性分子成像和非破坏性评估 3D器官结构。最初，其商业影响将主要集中在学术领域。 然而，随着肺生物工程技术的成熟， 在生物工程肺被批准用于 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.