Vascular Scaffolds for Tissue Engineering

描述(由申请人提供)：目前还没有有效的方法在器官级别的生物兼容基质材料中有效地构建三维血管网络。虽然微制造技术的发展已经取得了相当大的进步，以满足这些需求，但这些技术往往成本高昂，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换的工程化组织几乎是不可能的。这一探索性研究计划将通过开发先进的制造技术来满足这些需求，该技术能够快速且廉价地在组织支架材料内一步构建包含从100 nm到1 mm的通道尺寸的3D血管网络，并在整个器官基质尺寸范围内一步完成。这项工作将是第一次利用这些制造工艺来构建血管微通道网络，并将极大地提高构建组织工程器官替代物的能力。这些目标将通过以下具体目标来实现。目的1：建立一种全新的基于静电放电的技术，在塑料衬底上构建三维分形微通道网络，作为组织工程支架。目的2：在目标1构建的三维血管支架表面和内部进行细胞培养实验，以确定用于组织工程应用的最佳参数范围。在完成这一探索性研究计划后，一系列全新的制造工具将可用于在生物兼容的支架材料中构建具有功能的三维血管网络。这种先进的制造技术将第一次影响组织工程领域，使其能够在几乎任何实验室大规模生产用于整个器官置换的支架。据我们所知，这些基于静电放电的制造技术从未被应用于构建组织工程应用的血管结构。这些工具将使新一代工程化器官替代品的开发成为可能，这些器官替代品适合大规模生产，并提供前所未有的能力来模拟其天然同类的结构和功能。

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.