A hybrid biomimetic nanomatrix composed of electrospun polycaprolactone and bioactive peptide amphiphiles for cardiovascular implants.

A hybrid biomimetic nanomatrix composed of electrospun polycaprolactone and bioactive peptide amphiphiles for cardiovascular implants.
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DOI:
10.1016/j.actbio.2010.08.013
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发表时间:
2011-01
期刊:
影响因子:
9.7
通讯作者:
Jun, Ho-Wook
Jun, Ho-Wook
中科院分区:
工程技术1区
文献类型:
--
作者:
Andukuri, Adinarayana;Kushwaha, Meenakshi;Tambralli, Ajay;Anderson, Joel M.;Dean, Derrick R.;Berry, Joel L.;Sohn, Young Doug;Yoon, Young-Sup;Brott, Brigitta C.;Jun, Ho-Wook

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目前的心血管治疗受到内皮损失、再狭窄和血栓形成的限制。本研究的目的是开发一种仿生杂化纳米基质,其结合了静电纺丝聚己内酯(ePCL)纳米纤维与自组装肽两亲物(PA)的独特性能。ePCL纳米纤维具有互连的纳米多孔结构,但它们受到缺乏表面生物活性以控制细胞行为的阻碍。假设PA可以自组装到ePCL纳米纤维的表面上,并赋予它们天然内皮的特性。PA,其中包括连接到功能性亲水性肽序列的疏水性烷基尾,含有酶介导的可降解位点偶联到内皮细胞粘附配体(YIGSR)或聚赖氨酸(KKKKK)一氧化氮(NO)供体。成功地合成了两种不同的PA(PA-YIGSR和PA-KKKKK),并以90:10(YK)的比例混合以获得PA-YK。将PA-YK与纯NO反应生成PA-YK-NO,然后将其自组装到ePCL纳米纤维上,得到ePCL-PA-YK-NO杂化纳米基质。观察到从ePCL-PA-YK-NO成功释放NO。ePCL-YK和ePCL-PA-YK-NO可显著增强人脐静脉内皮细胞(HUVECs)的粘附。此外,ePCL-PA-YK-NO显示显著增加HUVECs的增殖和减少平滑肌细胞增殖。当与ePCL、ePCL-PA-YK和胶原对照相比时,ePCL-PA-YK-NO也显示出显著降低的血小板粘附。这些结果表明,这种杂化纳米基质在心血管植入物中具有巨大的潜在应用。
Current cardiovascular therapies are limited by loss of endothelium, restenosis, and thrombosis. The goal of this study is to develop a biomimetic hybrid nanomatrix that combines unique properties of electrospun polycaprolactone (ePCL) nanofibers with self-assembled peptide amphiphiles (PAs). ePCL nanofibers have interconnected nanoporous structures, but they are hampered by lack of surface bioactivity to control cellular behavior. It is hypothesized that PAs can self-assemble onto the surface of ePCL nanofibers and endow them with characteristic properties of native endothelium. PAs, which comprise hydrophobic alkyl tails attached to functional hydrophilic peptide sequences, contained enzyme-mediated degradable sites coupled to either endothelial cell adhesive ligands (YIGSR) or ploylysine (KKKKK) nitric oxide (NO) donors. Two different PAs (PA-YIGSR and PA-KKKKK) were successfully synthesized and mixed in a 90:10 (YK) ratio to obtain PA-YK. PA-YK was reacted with pure NO to develop PA-YK-NO, which was then self-assembled onto ePCL nanofibers to generate a hybrid nanomatrix, ePCL-PA-YK-NO. Uniform coating of self-assembled PA nanofibers on ePCL was confirmed by TEM. Successful NO release from ePCL-PA-YK-NO was observed. ePCL-YK and ePCL-PA-YK-NO showed significantly increased adhesion of human umbilical vein endothelial cells (HUVECs). Also, ePCL-PA-YK-NO showed significantly increased proliferation of HUVECs and reduced smooth muscle cell proliferation. ePCL-PA-YK-NO also displayed significantly reduced platelet adhesion when compared to ePCL, ePCL-PA-YK, and collagen control. These results indicate that this hybrid nanomatrix has great potential applications in cardiovascular implants.
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