Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35205, USA.
Biomaterials. 2010 Mar;31(7):1502-8. doi: 10.1016/j.biomaterials.2009.10.051. Epub 2009 Nov 12.
Cardiovascular disease is the number one cause of death in the United States. Deployment of stents and vascular grafts has been a major therapeutic method for treatment. However, restenosis, incomplete endothelialization, and thrombosis hamper the long term clinical success. As a solution to meet these current challenges, we have developed a native endothelial ECM mimicking self-assembled nanofibrous matrix to serve as a new treatment model. The nanofibrous matrix is formed by self-assembly of peptide amphiphiles (PAs), which contain nitric oxide (NO) donating residues, endothelial cell adhesive ligands composed of YIGSR peptide sequence, and enzyme-mediated degradable sites. NO was successfully released from the nanofibrous matrix rapidly within 48 h, followed by sustained release over period of 30 days. The NO releasing nanofibrous matrix demonstrated a significantly enhanced proliferation of endothelial cells (51+/-3% to 67+/-2%) but reduced proliferation of smooth muscle cells (35+/-2% to 16+/-3%) after 48 h of incubation. There was also a 150-fold decrease in platelet attachment on the NO releasing nanofibrous matrix (470+/-220 platelets/cm(2)) compared to the collagen-I (73+/-22 x 10(3)platelets/cm(2)) coated surface. The nanofibrous matrix has the potential to be applied to various cardiovascular implants as a self-assembled coating, thereby providing a native endothelial extracellular matrix (ECM) mimicking environment.
心血管疾病是美国头号死因。支架和血管移植物的部署一直是治疗的主要方法。然而,再狭窄、不完全内皮化和血栓形成阻碍了长期的临床成功。为了解决这些当前的挑战,我们开发了一种天然的内皮细胞外基质模拟自组装纳米纤维基质,作为一种新的治疗模型。纳米纤维基质是由肽两亲物(PAs)自组装形成的,其中包含一氧化氮(NO)供体残基、由 YIGSR 肽序列组成的内皮细胞黏附配体以及酶介导的可降解位点。NO 能够在 48 h 内从纳米纤维基质中快速释放,随后在 30 天的时间内持续释放。NO 释放纳米纤维基质在孵育 48 h 后,显著增强了内皮细胞的增殖(51+/-3%至 67+/-2%),但降低了平滑肌细胞的增殖(35+/-2%至 16+/-3%)。与涂覆有胶原蛋白-I(73+/-22 x 10(3)个血小板/cm(2))的表面相比,NO 释放纳米纤维基质上的血小板黏附减少了 150 倍(470+/-220 个血小板/cm(2))。该纳米纤维基质具有作为自组装涂层应用于各种心血管植入物的潜力,从而提供了一种天然的内皮细胞外基质(ECM)模拟环境。