The effects of heparin releasing hydrogels on vascular smooth muscle cell phenotype.
The effects of heparin releasing hydrogels on vascular smooth muscle cell phenotype.
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DOI：
10.1016/j.biomaterials.2009.08.004
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发表时间：
2009-10
期刊：
影响因子：
14
通讯作者：
Marchant, Roger E.
中科院分区：
文献类型：
--
作者：
Beamish, Jeffrey A.;Geyer, Leah C.;Haq-Siddiqi, Nada A.;Kottke-Marchant, Kandice;Marchant, Roger E.
设计了聚乙二醇二丙烯酸酯(PEGDA)水凝胶支架，通过控制肝素的释放来促进收缩的平滑肌细胞(SMC)的表型。通过量化游离肝素对SMC表型的影响，工程水凝胶提供肝素的控制释放，以及合成细胞黏附、肝素释放水凝胶促进SMC表型的收缩，对支架设计进行评估。肝素抑制SMC增殖，上调SMC收缩表型标志物的表达，包括平滑肌α肌动蛋白、钙蛋白和SM-22α，且呈剂量依赖关系(6ug/ml-3.2 mg/ml)。通过改变PEGDA分子量(Mw 1000-6000)和聚合时的浓度(10-30%w/w)来控制PEGDA水凝胶中肝素的释放，产生持续数小时到数周的释放曲线。从PEGDA凝胶中释放的肝素，为优化肝素加载和释放动力学而配制(30%w/w PEGDA，分子量3000)，刺激SMC上调收缩标志物mRNA。通过在优化的水凝胶库上聚合一层薄薄的水凝胶膜，与用于细胞附着的悬垂的RGD多肽聚合，制备了一种细胞指导支架结构。与对照组相比，种植在这些构建物上的SMC在培养3d后有更高的收缩标志物mRNA水平。这些结果表明，RGD修饰的、释放肝素的PEGDA凝胶可以作为细胞指导支架，促进SMC的收缩表型。
Poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds were engineered to promote contractile smooth muscle cell (SMC) phenotype via controlled release of heparin. The scaffold design was evaluated by quantifying the effects of free heparin on SMC phenotype, engineering hydrogels to provide controlled release of heparin, and synthesizing cell-adhesive, heparin releasing hydrogels to promote contractile SMC phenotype. Heparin inhibited SMC proliferation and up-regulated expression of contractile SMC phenotype markers, including smooth muscle alpha actin, calponin, and SM-22 alpha, in a dose-dependent fashion (6 ug/ml-3.2 mg/ml). Heparin release from PEGDA hydrogels was controlled by altering PEGDA molecular weight (MW 1000-6000) and concentration at polymerization (10-30% w/w), yielding release profiles ranging from hours to weeks in duration. Heparin released from PEGDA gels, formulated for optimized heparin loading and release kinetics (30% w/w PEGDA, MW 3000), stimulated SMCs to up-regulate contractile marker mRNA. A cell-instructive scaffold construct was prepared by polymerizing a thin hydrogel film, with pendent RGD peptides for cell attachment, over the optimized hydrogel depots. SMCs seeded on these constructs had elevated levels of contractile marker mRNA after 3 d of culture compared with SMCs on control constructs. These results indicate that RGD-modified, heparin releasing PEGDA gels can act as cell-instructive scaffolds that promote contractile SMC phenotype.
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