Fabricated Microvascular Networks

描述（由申请人提供）：制造的微血管网络。有效的血管供应对组织健康的重要性是普遍接受的。在开发为组织工程和其他治疗应用构建血管的策略时，重要的是要认识到，首先，新的血管系统必须快速地向靶组织提供足够的血流以保持细胞活力。我们已经发现，在体外形成的新的微血管可以在植入后的第一天内开始运送血液。然而，血流模式是非典型的，可能在许多天后才能建立正常血氧。延迟主要是由于植入时网络内缺乏组织以及开发新的成熟流入和流出通路所需的时间。我们假设，在植入前预先确定适当的网络组织将减少新微血管系统有效灌注组织所需的时间。我们已经建立了通用技术，利用直写组织打印工具来图案化和组织组织工程应用的组织成分。我们建议实施这项技术来设计和制造预先存在的流入和流出途径的预图案化的三维微血管网络。此外，我们将使用体外血管内灌注生物反应器系统来建立通过网络的流动，以在植入前进一步组织和成熟微血管网络。计算建模和生理分析用于指导设计策略，并表征体外和体内制造的血管的结构和功能。除了为组装预定的微血管网络提供一个使能技术平台外，这项工作还将为探索网络架构在血管功能中的重要性提供基础。

DESCRIPTION (provided by applicant): Fabricated Microvascular Networks. The importance of an effective vascular supply for tissue health is universally accepted. In developing strategies to build vasculatures for tissue engineering and other therapeutic applications, it is important to recognize that, foremost, the new vasculature must quickly provide sufficient blood flow to the target tissue to preserve cell viability. We have found that new microvessels formed in vitro can begin to carry blood within the first days following implantation. However, flow patterns are atypical and likely ineffective at establishing normoxia until many days later. The delay is primarily due to a lack of organization within the network at the time of implantation and the time needed to develop new mature inflow and outflow pathways. We hypothesize that pre-determining an appropriate network organization prior to implantation would reduce the amount of time needed for the new microvasculature to effectively perfuse a tissue. We have established generic technologies utilizing a direct-write tissue printing tool for patterning and organizing tissue components for tissue engineering applications. We propose to implement this technology to design and fabricate pre-patterned, 3-dimensional microvascular networks with pre-existing inflow and outflow pathways. Also, we will use an in vitro, intravascular-perfusion bioreactor system to establish flow through the networks to further organize and mature the microvascular networks prior to implantation. Computational modeling and physiological analyses serve to direct design strategies and characterize the architectures and functionality of the fabricated vasculatures both in vitro and in vivo. In addition to providing an enabling technology platform for assembling pre-determined microvascular networks, this work will provide a foundation from which to explore the importance of network architectures in vascular function.