The functionality of vascular networks within implanted prevascularized tissues is difficult to assess using traditional analysis techniques, such as histology. This is largely due to the inability to visualize hemodynamics in vivo longitudinally. Therefore, we have developed dynamic imaging methods to measure blood flow and hemoglobin oxygen saturation in implanted prevascularized tissues noninvasively and longitudinally. Using laser speckle imaging, multispectral imaging, and intravital microscopy, we demonstrate that fibrin-based tissue implants anastomose with the host (severe combined immunodeficient mice) in as short as 20 h. Anastomosis results in initial perfusion with highly oxygenated blood, and an increase in average hemoglobin oxygenation of 53%. However, shear rates in the preformed vessels were low (20.8±12.8 s−1), and flow did not persist in the vast majority of preformed vessels due to thrombus formation. These findings suggest that designing an appropriate vascular network structure in prevascularized tissues to maintain shear rates above the threshold for thrombosis may be necessary to maintain flow following implantation. We conclude that wide-field and microscopic functional imaging can dynamically assess blood flow and oxygenation in vivo in prevascularized tissues, and can be used to rapidly evaluate and improve prevascularization strategies.
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机译：使用传统的分析技术（例如组织学）很难评估植入的血管形成前组织内的血管网络的功能。这主要是由于无法纵向观察体内的血流动力学。因此，我们开发了动态成像方法来无创和纵向地测量植入的预血管化组织中的血流和血红蛋白氧饱和度。使用激光散斑成像，多光谱成像和活体显微镜检查，我们证明了基于纤维蛋白的组织在短短20h内即可与宿主（严重合并免疫缺陷的小鼠）吻合。吻合导致高氧合血液的初始灌注，平均血红蛋白氧合增加53％。然而，在预制容器中的剪切速率较低（20.8±12.8 s -1 ），并且由于形成血栓，在大多数预制容器中流动没有持续。这些发现表明，在植入前，在血管形成前的组织中设计适当的血管网络结构，以保持剪切速率高于血栓形成阈值可能是必要的。我们得出的结论是，宽视野和微观功能成像可以动态评估血管内预血管组织中的血流量和体内氧合，并可用于快速评估和改善血管前策略。
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