The effect of controlled release of PDGF-BB from heparin-conjugated electrospun PCL/gelatin scaffolds on cellular bioactivity and infiltration.

The effect of controlled release of PDGF-BB from heparin-conjugated electrospun PCL/gelatin scaffolds on cellular bioactivity and infiltration.
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DOI:
10.1016/j.biomaterials.2012.06.017
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发表时间:
2012-10
期刊:
影响因子:
14
通讯作者:
Lee SJ
Lee SJ
中科院分区:
工程技术1区
文献类型:
--
作者:
Lee J;Yoo JJ;Atala A;Lee SJ

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开发了肝素缀合的电纺聚(ε-己内酯)(PCL)/明胶支架,以提供血小板衍生生长因子-BB(PDGF-BB)的受控释放,并允许该分子的延长的生物活性。将PCL和明胶的混合物静电纺丝成三种不同的形态。接下来,肝素分子与支架的反应性表面结合。这种肝素缀合的支架允许通过静电相互作用固定PDGF-BB。体外PDGF-BB释放曲线表明,PDGF-BB对非肝素化支架的被动物理吸附导致PDGF-BB在5天内的初始爆发释放,然后趋于平稳。然而,PDGF-BB和肝素缀合的支架之间的静电相互作用引起PDGF-BB在20天的过程中持续释放,而没有初始爆发。此外,PDGF-BB,这是强烈结合到肝素结合的支架增强平滑肌细胞(SMC)增殖。此外,与由较小直径纤维组成的支架或不释放PDGF-BB的支架相比,由3.0 μm直径纤维组成的支架用PDGF-BB固定化加速了SMC向支架中的浸润。我们得出结论,支架中的大孔结构和肝素介导的PDGF-BB递送的组合通过协同的物理和化学线索提供了最有效的细胞相互作用。
Heparin-conjugated electrospun poly(ε-caprolactone) (PCL)/gelatin scaffolds were developed to provide controlled release of platelet-derived growth factor-BB (PDGF-BB) and allow prolonged bioactivity of this molecule. A mixture of PCL and gelatin was electrospun into three different morphologies. Next, heparin molecules were conjugated to the reactive surface of the scaffolds. This heparin-conjugated scaffold allowed the immobilization of PDGF-BB via electrostatic interaction. In vitro PDGF-BB release profiles indicated that passive physical adsorption of PDGF-BB to non-heparinized scaffolds resulted in an initial burst release of PDGF-BB within 5 days, which then leveled off. However, electrostatic interaction between PDGF-BB and the heparin-conjugated scaffolds gave rise to a sustained release of PDGF-BB over the course of 20 days without an initial burst. Moreover, PDGF-BB that was strongly bound to the heparin-conjugated scaffolds enhanced smooth muscle cell (SMC) proliferation. In addition, scaffolds composed of 3.0 µm diameter fibers that were immobilized with PDGF-BB accelerated SMC infiltration into the scaffold when compared to scaffolds composed of smaller diameter fibers or scaffolds that did not release PDGF-BB. We concluded that the combination of the large pore structure in the scaffolds and the heparin-mediated delivery of PDGF-BB provided the most effective cellular interactions through synergistic physical and chemical cues.
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