Hashi Craig K, Zhu Yiqian, Yang Guo-Yuan, Young William L, Hsiao Benjamin S, Wang Karin, Chu Benjamin, Li Song
Department of Bioengineering and Center for Tissue Bioengineering, University of California, Berkeley, CA 94720, USA.
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11915-20. doi: 10.1073/pnas.0704581104. Epub 2007 Jul 5.
Nanostructured biomaterials have tremendous potential for tissue engineering. However, the performance and integration of the nanomaterials in vivo are not well understood. A challenge in vascular tissue engineering is to develop optimal scaffolds and establish expandable cell sources for the construction of tissue-engineered vascular grafts that are nonthrombogenic and have long-term patency. Here, we used tissue-engineered vascular grafts as a model to demonstrate the potential of combining nanofibrous scaffolds and bone marrow mesenchymal stem cells (MSCs) for vascular tissue engineering. Biodegradable nanofibrous scaffolds with aligned nanofibers were used to mimic native collagen fibrils to guide cell organization in vascular grafts. The results from artery bypass experiments showed that nanofibrous scaffolds allowed efficient infiltration of vascular cells and matrix remodeling. Acellular grafts (without MSCs) resulted in significant intimal thickening, whereas cellular grafts (with MSCs) had excellent long-term patency and exhibited well organized layers of endothelial cells (ECs) and smooth muscle cells (SMCs), as in native arteries. Short-term experiments showed that nanofibrous scaffolds alone induced platelet adhesion and thrombus formation, which was suppressed by MSC seeding. In addition, MSCs, as ECs, resisted platelet adhesion in vitro, which depended on cell-surface heparan sulfate proteoglycans. These data, together with the observation on the short-term engraftment of MSCs, suggest that the long-term patency of cellular grafts may be attributed to the antithrombogenic property of MSCs. These results demonstrate several favorable characteristics of nanofibrous scaffolds, the excellent patency of small-diameter nanofibrous vascular grafts, and the unique antithrombogenic property of MSCs.
纳米结构生物材料在组织工程方面具有巨大潜力。然而，纳米材料在体内的性能和整合情况尚未得到充分了解。血管组织工程面临的一个挑战是开发最佳支架，并建立可扩展的细胞来源，以构建非血栓形成且具有长期通畅性的组织工程血管移植物。在此，我们以组织工程血管移植物为模型，展示了将纳米纤维支架与骨髓间充质干细胞（MSCs）相结合用于血管组织工程的潜力。具有排列纳米纤维的可生物降解纳米纤维支架被用于模拟天然胶原纤维，以引导血管移植物中的细胞组织。动脉搭桥实验结果表明，纳米纤维支架允许血管细胞有效浸润和基质重塑。无细胞移植物（不含MSCs）导致显著的内膜增厚，而细胞移植物（含MSCs）具有出色的长期通畅性，并呈现出如天然动脉中那样组织良好的内皮细胞（ECs）和平滑肌细胞（SMCs）层。短期实验表明，单独的纳米纤维支架会诱导血小板黏附和血栓形成，而MSC接种可抑制这种情况。此外，MSCs作为ECs在体外可抵抗血小板黏附，这取决于细胞表面的硫酸乙酰肝素蛋白聚糖。这些数据，连同对MSCs短期植入的观察结果，表明细胞移植物的长期通畅性可能归因于MSCs的抗血栓形成特性。这些结果证明了纳米纤维支架几个有利的特性、小直径纳米纤维血管移植物出色的通畅性以及MSCs独特的抗血栓形成特性。
