• 文献标题:   Engineered-Macrophage Induced Endothelialization and Neutralization via Graphene Quantum Dot-Mediated MicroRNA Delivery to Construct Small-Diameter Tissue-Engineered Vascular Grafts
  • 文献类型:   Article
  • 作  者:   WEI KY, LIU FL, YANG JY, HUO D, GUAN G, LI YZ, YANG GY, WANG TR, WANG YQ, NIE ZQ, ZENG W, ZHU CH
  • 作者关键词:   tebv, graphene quantum dot, endothelialization, gene delivery, vegf, macrophage
  • 出版物名称:   JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
  • ISSN:   1550-7033 EI 1550-7041
  • 通讯作者地址:   Third Mil Med Univ
  • 被引频次:   2
  • DOI:   10.1166/jbn.2019.2787
  • 出版年:   2019

▎ 摘  要

Rapid endothelialization of tissue-engineered blood vessels (TEBVs) is an essential strategy to inhibit thrombosis, chronic inflammation and intimal hyperplasia after transplantation into the body. Monocytes will be recruited to the transplantation site and converted to macrophages after TEBV implantation. Macrophages play an important role in angiogenesis; however, whether engineered macrophages can be utilized to promote rapid endothelialization of TEBVs remains unclear. Thus, a cell bioreactor that can engineer macrophages via graphene quantum dot (GQD)-mediated microRNA (miR) delivery was built in the TEBV. Briefly, GQD-miR-150 linked by disulfide bonds was adopted to functionalize both the inner and outer TEBVs. The GOD-miR-150 conjugation as an intracellular gene delivery system was taken up by macrophages. Under the protection of GQDs, miR-150 was transfected into the cytosol, allowing continuous secretion of vascular endothelial growth factor (VEGF) via upregulation of HIF-1 alpha protein expression, and promoted the migration of endothelial cells (ECs) in vitro. An in vivo study showed a rapid endothelialization of the inner TEBVs after transplantation for 7 days, especially a holonomic endothelial layer after 30 days. For the outer TEBVs, neovascularization (vasa vasorum) accompanied by nerve growth was observed around the adventitia on day 90. In conclusion, the designed cell bioreactor consisting of GQD-miR-engineered macrophages can effectively promote endothelialization and neuralization in vivo for TEBVs.