Harvard-MIT Division of Health Sciences and Technology, David H. Koch Institute for Integrative Cancer Research, and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Biomaterials. 2013 Dec;34(38):10007-15. doi: 10.1016/j.biomaterials.2013.09.039. Epub 2013 Sep 27.
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.
一个由不同实质和血管隔室组成的可生物降解微血管支架,由可渗透的膜界面分隔,该支架被构思、制造、细胞化并植入。该设备设计了可灌注的微流道,尺寸约为 100μm,以模拟小血管,并与相邻实质空间具有高界面面积,以实现隔室之间的物质传递。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其具有稳健的机械完整性。体外研究表明,在实质空间中培养的人骨骼肌细胞发生了分化,由于灌流液中肌毒性药物的跨膜转运,肌肉细胞的存活率降低了 90%,并且人内皮细胞对微血管进行了接种。将支架植入裸鼠的皮下和腹腔内,无论是没有还是有外源性细胞,进行的体内研究表明,膜界面发生了生物降解,并且宿主血细胞渗透到微血管中。这种模块化、可植入的支架可以作为构建规模和临床相关性不断增加的组织构建体的基础。