Vascular Scaffolds for Tissue Engineering

描述（由申请人提供）：目前还没有有效的方法在生物相容性基质材料中高效地构建器官水平尺寸的三维血管网络。尽管在解决这些需求的微加工技术的发展方面取得了相当大的进展，但这些技术往往成本高昂，而且速度太慢，无法实现大规模生产。除非在支架制造速度和特征分辨率方面取得重大进展，否则培养和生长适合器官替代的工程组织几乎是不可能的。这个探索性研究项目将通过开发先进的制造技术来解决这些需求，该技术能够快速、廉价地在组织支架材料中构建3-D血管网络，其通道尺寸从100纳米到1毫米不等，只需一步，就能达到整个器官基质的尺寸。这项工作将是这些制造工艺首次被用于血管微通道网络的构建，并将大大提高构建组织工程器官替代品的能力。这些目标将通过以下具体目标来实现。目标1：建立一种全新的基于静电放电的技术，使3d分形微通道网络在塑料基板上的制造成为可能，用于组织工程支架。目标2：在目标1中构建的三维血管化支架的表面和内部进行细胞培养实验，以建立用于组织工程应用的最佳参数范围。在完成这个探索性研究项目后，一个全新的制造工具家族将可用于在生物相容性支架材料中构建功能三维血管网络。这种先进的制造技术将影响组织工程领域，因为它首次使在几乎任何实验室大规模生产全器官替代支架成为可能。据我们所知，这些基于静电放电的制造技术从未应用于组织工程中血管结构的构建。这些工具将使新一代工程器官替代品的发展成为可能，适合大规模生产，并提供前所未有的能力来模仿其天然对应物的结构和功能。

DESCRIPTION (provided by applicant): There is currently no effective process to efficiently construct 3-D vascular networks in biocompatible substrate materials at organ-level size scales. Although considerable progress has been made in the development of microfabrication technologies to address these needs, these techniques are often costly and much too slow to be practical for mass-production. Unless significant advances in scaffold fabrication speed and feature resolution can be achieved, it will be virtually impossible to culture and grow engineered tissues suitable for organ replacement. This exploratory research program will address these needs by developing advanced fabrication technologies capable of rapidly and inexpensively constructing 3-D vascular networks incorporating channel sizes ranging from 100 nm to 1 mm within tissue scaffold materials in a single step at whole-organ substrate size scales. This work will be the first time these fabrication processes have been harnessed for the construction of vascular microchannel networks, and will greatly enhance the ability to construct tissue engineered organ replacements. These goals will be accomplished through the following Specific Aims. Aim 1: Establish an entirely new electrostatic discharge-based technology to enable fabrication of 3-D fractal microchannel networks in plastic substrates for use as tissue engineering scaffolds. Aim 2: Perform cell culture experiments both on the surface of and within the 3-D vascularized scaffolds constructed in Aim 1 in order to establish the optimal range of parameters for use in tissue engineering applications. Upon completion of this exploratory research program, an entirely new family of fabrication tools will be available for construction of functional 3-D vascular networks in biocompatible scaffold materials. This advanced fabrication technology will impact the field of tissue engineering by, for the first time, making it feasible to mass produce scaffolds for whole-organ replacement in virtually any laboratory. To our knowledge, these electrostatic discharge-based fabrication techniques have never been applied toward construction of vascular structures for tissue engineering applications. These tools will enable the development of a new generation of engineered organ replacements, suitable for mass production and offering an unprecedented capability to mimic the structure and function of their natural counterparts.