In vivo engineering of a human vasculature for bone tissue engineering applications.
In vivo engineering of a human vasculature for bone tissue engineering applications.
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DOI：
10.1111/j.1582-4934.2008.00418.x
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发表时间：
2009-09
影响因子：
5.3
通讯作者：
Finkenzeller G
中科院分区：
文献类型：
--
作者：
Steffens L;Wenger A;Stark GB;Finkenzeller G
骨等三维海量组织的新生血管是组织工程应用中的一个重要挑战。移植后形成预形成的血管丛可维持细胞活性，促进血管生成。为促进骨组织工程应用中的血管生成，我们开发了一种由人原代内皮细胞和人原代成骨细胞组成的三维球状共培养系统。在这项研究中，我们研究了工程化植入物的存活和体内血管形成。将内皮细胞球体与HOBS在纤维蛋白中共培养，种植到由加工过的牛松质骨(PBCB)组成的支架中。通过两种不同的体内实验：鸡胚绒毛尿囊膜(CAM)模型和严重联合免疫缺陷(SCID)小鼠模型，评价了细胞种植支架的血管生成能力。在这两种检测中，都可以检测到由灌流的人类新生细胞组成的复杂三维网络的发展。皮下移植到免疫缺陷小鼠体内后，新形成的人类血管系统通过招募小鼠平滑肌α-肌动蛋白阳性的壁细胞并与小鼠血管系统吻合而稳定下来。我们的结论是，该内皮细胞球体系统可用于在活体内创建一个功能性的灌流血管网络。这一发现表明，在PBCB支架提供的骨传导环境中，这一过程在共植入的原代成骨细胞存在下高效进行，这表明该系统可能适合于改善骨组织工程中的血管形成。
The neovascularization of three-dimensional voluminous tissues, such as bone, represents an important challenge in tissue engineering applications. The formation of a preformed vascular plexus could maintain cell viability and promote vascularization after transplantation. We have developed a three-dimensional spheroidal coculture system consisting of human primary endothelial cells and human primary osteoblasts (hOBs) to improve angiogenesis in bone tissue engineering applications. In this study, we investigated the survival and vascularization of the engineered implants in vivo. Endothelial cell spheroids were cocultured with hOBs in fibrin and seeded into scaffolds consisting of processed bovine cancellous bone (PBCB). The cell-seeded scaffolds were evaluated for their angiogenic potential in two different in vivo assays: the chick embryo chorioallantoic membrane (CAM) model and the severe combined immunodeficiency disorder (SCID) mouse model. In both assays, the development of a complex three-dimensional network of perfused human neovessels could be detected. After subcutaneous implantation into immunodeficient mice, the newly formed human vasculature was stabilized by the recruitment of murine smooth muscle α-actin-positive mural cells and anastomoses with the mouse vasculature. We conclude that this endothelial cell spheroid system can be used to create a network of functional perfused blood vessels in vivo. The finding that this process takes place with high efficacy in the presence of co-implanted primary osteoblasts and in an osteoconductive environment provided by the PBCB scaffold, suggests that this system may be suitable for improving vascularization in bone tissue engineering.