3D Bioprinting of Engineered Tissue Flaps with Hierarchical Vessel Networks (VesselNet) for Direct Host-To-Implant Perfusion
3D Bioprinting of Engineered Tissue Flaps with Hierarchical Vessel Networks (VesselNet) for Direct Host-To-Implant Perfusion
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DOI：
10.1002/adma.202102661
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发表时间：
2021-09-12
影响因子：
29.4
通讯作者：
Levenberg, Shulamit
中科院分区：
文献类型：
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作者：
Szklanny, Ariel A.;Machour, Majd;Levenberg, Shulamit
工程分级脉管系统对于创建可植入的功能性厚组织至关重要。目前的方法侧重于制造用于植入的中尺度血管或分层微血管体外模型，但尚未实现创建工程组织瓣的组合方法。在这里，毫米级血管支架和 3D 生物打印血管化组织相互连接，创建用于植入的完全工程化的分层血管结构。使用人类胶原蛋白生物墨水，内皮细胞和支持细胞在生物打印组织中自发形成微血管网络。牺牲模具用于创建聚合物血管样支架和在其管腔中接种的内皮细胞，形成天然内皮细胞。在血管化水凝胶内组装内皮化支架会刺激生物打印的脉管系统和内皮细胞协同创建血管，从而使组织能够通过支架内腔进行灌注。使用袖套显微外科手术方法，工程组织直接与大鼠股动脉吻合，促进植入组织内丰富的宿主脉管系统。体内两周后，对比微计算机断层扫描成像和外植工程组织的凝集素灌注验证了宿主向内生长脉管系统的功能。此外，分层血管网络（VesselNet）支持心肌细胞的体外功能。最后，所提出的方法扩展到模拟具有类似原生毫米血管的复杂结构。这项工作提出了一种新颖的策略，旨在创建完全工程化的患者特异性厚组织瓣。
Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel-like scaffolds and endothelial cells seeded in their lumen form native-like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites the bioprinted vasculature and endothelium to cooperatively create vessels, enabling tissue perfusion through the scaffold lumen. Using a cuffing microsurgery approach, the engineered tissue is directly anastomosed with a rat femoral artery, promoting a rich host vasculature within the implanted tissue. After two weeks in vivo, contrast microcomputer tomography imaging and lectin perfusion of explanted engineered tissues verify the host ingrowth vasculature's functionality. Furthermore, the hierarchical vessel network (VesselNet) supports in vitro functionality of cardiomyocytes. Finally, the proposed approach is expanded to mimic complex structures with native-like millimetric vessels. This work presents a novel strategy aiming to create fully-engineered patient-specific thick tissue flaps.