Department of Biomedical Engineering, University of Rochester, 308 Goergen Hall, P.O. Box 270168, Rochester, NY, 14627, USA.
Department of Pharmacology and Physiology, University of Rochester, 601 Elmwood Avenue, Box 711, Rochester, NY, 14642, USA.
Sci Rep. 2023 Sep 26;13(1):16082. doi: 10.1038/s41598-023-43299-0.
Strategies to fabricate microvascular networks that structurally and functionally mimic native microvessels are needed to address a host of clinical conditions associated with tissue ischemia. The objective of this work was to advance a novel ultrasound technology to fabricate complex, functional microvascular networks directly in vivo. Acoustic patterning utilizes forces within an ultrasound standing wave field (USWF) to organize cells or microparticles volumetrically into defined geometric assemblies. A dual-transducer system was developed to generate USWFs site-specifically in vivo through interference of two ultrasound fields. The system rapidly patterned injected cells or microparticles into parallel sheets within collagen hydrogels in vivo. Acoustic patterning of injected endothelial cells within flanks of immunodeficient mice gave rise to perfused microvessels within 7 days of patterning, whereas non-patterned cells did not survive. Thus, externally-applied ultrasound fields guided injected endothelial cells to self-assemble into perfused microvascular networks in vivo. These studies advance acoustic patterning towards in vivo tissue engineering by providing the first proof-of-concept demonstration that non-invasive, ultrasound-mediated cell patterning can be used to fabricate functional microvascular networks directly in vivo.
需要构建在结构和功能上模拟天然微血管的微血管网络的策略，以解决与组织缺血相关的多种临床情况。本工作的目的是推进一种新的超声技术，直接在体内构建复杂的功能性微血管网络。声图案利用超声驻波场（USWF）内的力将细胞或微颗粒体积组织成定义的几何组装体。开发了一种双换能器系统，通过两个超声场的干涉，在体内特异性地产生 USWF。该系统可快速将注入的细胞或微颗粒在体内的胶原水凝胶中制成平行薄片。在免疫缺陷小鼠的侧腹内对注入的内皮细胞进行声图案化处理，可在图案化后 7 天内产生灌注的微血管，而非图案化的细胞则无法存活。因此，外部施加的超声场引导注入的内皮细胞在体内自行组装成灌注的微血管网络。这些研究通过提供第一个概念验证，证明非侵入性的超声介导的细胞图案化可用于直接在体内构建功能性微血管网络，从而推动声图案化在体内组织工程中的发展。
