Wang Ying, Kibbe Melina R, Ameer Guillermo A
Biomedical Engineering Department, Northwestern University, Evanston, IL 60208.
Division of Vascular Surgery, Feinberg School of Medicine, Northwestern University Chicago, IL 60611 ; Institute for Bionanotechnology in Medicine, Northwestern University, Chicago, IL 60611.
Biomater Sci. 2013 Jun;1(6):625-632. doi: 10.1039/C3BM00169E.
The delivery of nitric oxide (NO) has important applications in medicine, especially for procedures that involve the vasculature. We report photo-curable biodegradable poly(diol citrate) elastomers capable of slow release of NO. A methacrylated poly(diol citrate) macromonomer was prepared by polycondensation of citric acid with 1, 8-octanediol or 1, 12-dodecanediol followed by functionalization with 2-aminoethyl methacrylate. A miscible NO donor, diazeniumdiolated N, N-diethyldiethylenetriamine, was synthesized and incorporated into the polymer matrix. An elastomeric network was obtained via photo-polymerization of macromonomers upon UV irradiation within three minutes. Films and tubes of the NO-releasing crosslinked macromonomers exhibited strong tensile strength and radial compressive strength, respectively. They also exhibited cell compatibility and biodegradability in vitro. Sustained NO release under physiological conditions was achieved for at least one week. NO release enhanced the proliferation of human umbilical vein endothelial cells but inhibited the proliferation of human aortic smooth muscle cells. Photo-polymerizable NO-releasing materials provide a new approach for the localized and sustained delivery of NO to treat thrombosis and restenosis in the vasculature.
一氧化氮(NO)的递送在医学领域有着重要应用,尤其适用于涉及脉管系统的手术。我们报道了能够缓慢释放NO的光固化可生物降解聚(柠檬酸二醇酯)弹性体。通过柠檬酸与1,8 - 辛二醇或1,12 - 十二烷二醇缩聚,随后用甲基丙烯酸2 - 氨基乙酯官能化,制备了甲基丙烯酸化聚(柠檬酸二醇酯)大分子单体。合成了一种可混溶的NO供体——重氮二醇化的N,N - 二乙基二乙烯三胺,并将其掺入聚合物基质中。通过在紫外线照射下三分钟内大分子单体的光聚合获得弹性体网络。释放NO的交联大分子单体的薄膜和管材分别表现出很强的拉伸强度和径向抗压强度。它们在体外还表现出细胞相容性和生物降解性。在生理条件下实现了至少一周的持续NO释放。NO释放增强了人脐静脉内皮细胞的增殖,但抑制了人主动脉平滑肌细胞的增殖。可光聚合的NO释放材料为局部和持续递送NO以治疗脉管系统中的血栓形成和再狭窄提供了一种新方法。