Ultrasound standing wave fields for vascular tissue engineering

描述（由申请人提供）： 创建在结构上和功能上模拟天然微血管系统的人造微血管网络对于制造和 该研究将为多种生物工程组织的存活提供新的技术支持，并将为药物发现、产品测试和毒理学筛选提供现实的具有成本效益的体外模型。我们最近开发了一种创新的、基于非侵入性超声的方法，在3D水凝胶内对细胞进行空间图案化，并证明了将超声技术转化为微血管组织工程的可行性。我们已经表明，与超声驻波场（USWF）相关的声辐射力可以快速组织细胞在三维胶原蛋白凝胶内形成不同的多细胞平面带。USWF诱导的内皮细胞图案化快速启动整个水凝胶体积中复杂的分支血管网络的组装。重要的是，可以通过声场的设计来控制形成的速率以及所得微血管网络的形态。该项目的目标是推进USWF技术作为一种多功能、非侵入性方法在体外使水凝胶血管化，最终目标是将该技术转化为原位血管化。为此，我们将（1）确定刺激微血管组装和控制微血管结构的USWF暴露参数，（2）确定影响结构的关键生物学参数， USWF-制造的微血管网络的功能，并优化它们在体外和原位制造中的使用，和（3）评估体外和原位制造的USWF水凝胶构建体的体内性能。基于超声的非侵入性技术可以在体外或原位将细胞快速组织成不同的几何图案，将广泛适用于细胞和组织类型，因此，预计将对推进组织工程和再生医学产生广泛影响。

DESCRIPTION (provided by applicant): Creating artificial microvessel networks that structurally and functionally mimic the native microvasculature is critical for the fabrication and survival of a wide range of bioengineered tissues, and will also provide realistic cost-effective i vitro models for drug discovery, product testing and toxicology screening. We have recently developed an innovative, non-invasive ultrasound-based method to spatially pattern cells within 3D hydrogels, and have demonstrated the feasibility of translating ultrasound technologies to microvascular tissue engineering. We have shown that acoustic radiation forces associated with ultrasound standing wave fields (USWF) can rapidly organize cells into distinct multicellular planar bands within 3D collagen gels. USWF-induced patterning of endothelial cells rapidly initiates the assembly of complex, branching vessel networks throughout the volume of the hydrogel. Importantly, the rate of formation as well as the morphology of resultant microvascular networks can be controlled by design of the acoustic field. The goal of this project is to advance the use of USWF technologies as a versatile, non-invasive method to vascularize hydrogels in vitro, with the ultimate goal of translating this technique to in situ vascularization. To do so, w will (1) identify USWF exposure parameters that stimulate microvessel assembly and control microvessel structure, (2) identify critical biological parameters that influence the structure and function of USWF-fabricated microvascular networks, and optimize their usage for in vitro and in situ fabrication, and (3) assess the in vivo performance of USWF hydrogel constructs fabricated in vitro and in situ. Non-invasive ultrasound-based technologies that can rapidly organize cells into distinct geometric patterns, either in vitro or in situ, will be broadly applicable across cel and tissue types, and thus, are expected to have a wide impact on advancing tissue engineering and regenerative medicine.