Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Biomaterials. 2012 Oct;33(28):6709-20. doi: 10.1016/j.biomaterials.2012.06.017. Epub 2012 Jul 6.
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.
肝素接枝静电纺聚(ε-己内酯)(PCL)/明胶支架被开发出来,以提供血小板衍生生长因子-BB(PDGF-BB)的控制释放,并允许该分子的延长生物活性。PCL 和明胶的混合物被静电纺成三种不同的形态。接下来,肝素分子被接枝到支架的反应性表面上。这种肝素接枝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,非肝素化支架上 PDGF-BB 的被动物理吸附导致 PDGF-BB 在 5 天内的初始突释,然后趋于稳定。然而,PDGF-BB 与肝素接枝支架之间的静电相互作用导致 PDGF-BB 在 20 天内持续释放,而没有初始突释。此外,与肝素接枝支架强结合的 PDGF-BB 增强了平滑肌细胞(SMC)的增殖。此外,与含有较小直径纤维的支架或不释放 PDGF-BB 的支架相比,固定有 PDGF-BB 的 3.0μm 直径纤维组成的支架加速了 SMC 渗透到支架中。我们得出结论,支架中的大孔结构与肝素介导的 PDGF-BB 传递的结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。