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A Biodegradable Microvessel Scaffold as a Framework to EnableVascular Support of Engineered Tissues

机译:可生物降解的微血管支架作为框架工程组织的血管支持

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摘要

A biodegradable microvessel scaffold comprised of distinct parenchymal and vascular compartments separated by a permeable membrane interface was conceptualized, fabricated, cellularized, and implanted. The device was designed with perfusable microfluidic channels on the order of 100 µm to mimic small blood vessels, and high interfacial area to an adjacent parenchymal space to enable transport between the compartments. Poly(glycerol sebacate) (PGS) elastomer was used to construct the microvessel framework, and various assembly methods were evaluated to ensure robust mechanical integrity. In vitro studies demonstrated the differentiation of human skeletal muscle cells cultured in the parenchymal space, a 90% reduction in muscle cell viability due to trans-membrane transport of a myotoxic drug from the perfusate, and microvessel seeding with human endothelial cells. In vivo studies of scaffolds implanted subcutaneously and intraperitoneally, without or with exogenous cells, into nude rats demonstrated biodegradation of the membrane interface and host blood cell infiltration of the microvessels. This modular, implantable scaffold could serve as a basis for building tissue constructs of increasing scale and clinical relevance.
机译:构想,制作,细胞化和植入由可渗透的膜界面分隔的不同的实质和血管室组成的可生物降解的微血管支架。该设备设计有100微米量级的可灌注微流体通道,可模仿小血管,并具有至邻近实质空间的高界面面积,从而能够在隔室之间进行运输。聚癸二酸甘油酯(PGS)弹性体用于构建微血管框架,并评估了各种组装方法以确保坚固的机械完整性。体外研究表明,在实质空间中培养的人骨骼肌细胞的分化,由于从灌注液中穿过肌毒性药物的跨膜转运,以及人血管内皮细胞的微血管接种,肌肉细胞活力降低了90%。裸鼠皮下和腹膜内植入有或没有外源细胞的支架的体内研究表明,膜界面的生物降解和微血管的宿主血细胞浸润。这种模块化的可植入支架可以作为构建规模和临床相关性日益增加的组织构建体的基础。

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