【作者】 刘威；

【导师】 陈红； 武照强；

【作者基本信息】 苏州大学 ， 材料科学与工程， 2015， 硕士

【摘要】 本论文主要是基于静电纺丝技术,制备了具有纤溶功能的纳米纤维膜材料。一方面,制备了表面含有ε-赖氨酸配体的功能纳米纤维膜,通过纤维膜材料表面固定的ε-赖氨酸配体特异性结合人体纤溶系统中的核心蛋白质血纤维蛋白溶酶原(Plg)和组织型血纤维蛋白溶酶原激活剂(t-PA),并利用电纺纤维膜大的比表面积和高的孔隙率实现了材料对Plg和t-PA的高负载量,从而有效溶解材料表面形成的初生血栓,提高了材料的血液相容性。另一方面,通过同轴静电纺丝方法,制备了内芯中负载t-PA的“核-壳”结构纳米纤维,以获得可长时间持续释放t-PA的血液接触材料。研究内容如下:1.基于静电纺丝技术,提出了一种于材料表面方便负载t-PA的方法。我们首先设计合成了一种ε-赖氨酸配体修饰的PVA(PVA-Lys),然后通过静电纺丝技术一步法便制备了ε-赖氨酸配体功能化的PVA/PVA-Lys纤维膜。该纤维膜能够很好地抑制非特异性蛋白纤维蛋白原(Fg)的吸附并有着良好的生物相容性,通过纤维膜上ε-赖氨酸配体对t-PA之间的特异性亲和力和电纺膜大的比表面积特点有效地实现了t-PA的负载。血浆复钙化实验表明,纤维膜上t-PA的释放可有效溶解初生血栓。该方法最大的特点是:通过在电纺过程中,简单地改变电纺溶液中PVA-Lys的加入量,就可以方便地调控t-PA在纤维膜上的负载量。2.基于席夫碱反应,提出了一种适用于多种基材表面的ε-赖氨酸配体功能化改性方法。受醛基和氨基之间的席夫碱反应,可形成稳定聚合物凝胶的启发,我们首先设计合成了两种侧链上分别带有醛基的均聚物P(-CHO)和氨基的ε-赖氨酸共聚物P(-NH2),并以乙酸纤维素(CA)为模型基材,利用静电纺丝技术制备了CA的纳米纤维膜,然后将CA纤维膜依次浸泡在P(-CHO)和P(-NH2)的水溶液中,通过这种简单的温和的水相浸泡法,就可得到含有ε-赖氨酸残基聚合物凝胶层改性的纳米纤维膜。利用ε-赖氨酸配体和Plg之间的特异性亲和力及电纺膜大的比表面积效应,其能够大量吸附血浆中的Plg,从而简便地实现了具有潜在纤溶功能材料表面的构建。3.基于同轴静电纺丝方法,以具有良好生物相容性和可降解性的CA为外层材料,制备了内芯中负载t-PA的“核-壳”结构纳米纤维。TEM测试表明t-PA位于纤维的内层,Bradford法测试结果显示纤维膜中负载的t-PA能够长时间的持续缓慢释放。更多还原

【Abstract】 In this thesis, we successfully prepared nanofibrous membrane materials with fibrinolytic function based on the electrospinning technology. On the one hand, we fabricated lysine ligand-functionalized nanofibrous membrane. Through the lysine ligand existing on the surface, the membrane could specifically bind plasminogen(Plg) and tissue plasminogen activator(t-PA) which are the core proteins of the natural fibrinolytic system. Moreover, owing to the high surface to volume ratio and effective porosity of the electrospun mats, the material had a high loading for both Plg and t-PA. As a result, it could efficiently lyse the primary thrombus that formed on the surface. On the other hand, we obtained core-shell structure electrospun nanofibers for sustained release of t-PA via the coaxial electrospinning method. The main content is as follows:1. Based on the electrospinning technology, we proposed a convenient method for t-PA loading on the material surface. We firstly synthesized a lysine ligand-modified PVA(PVA-Lys) and then fabricated lysine ligand-functionalized PVA/PVA-Lys nanofibrous membrane through the one-step electrospinning aqueous solution of PVA and PVA-Lys. The electrospun mats showed good resistance to non-specific protein adsorption of fibrinogen and excellent biocompatibility with L929 cells using the MTT assay. A highly specific tethering of t-PA was facilitated by the lysine ligand-functionalized surface through a molecular recognition of t-PA to the lysine ligand. Moreover, the t-PA anchorage to the PVA/PVA-Lys mats could be easily released when exposed to plasma, and could efficiently lyse the formed-clot in an in vitro plasma assay. In particular, the quantities of t-PA tethered on the electrospun mats could easily be regulated by simply varying the blend ratio of PVA and PVA-Lys in the electrospinning process.2. Based on Schiff base reaction, we demonstrated a mild and effective approach for lysine ligand-modified electrospun mats surface by a simple dipping method. We firstly synthesized two polymers P(-CHO) and P(-NH2) with aldehyde and lysine ligand on the side chain, respectively. After that, the lysine-functionalization of the cellulose acetate nanofibrous membrane, which was obtained by electrospinning, was performed by sequentially dipping in the P(-CHO) and P(-NH2) aqueous solutions. The modified nanofibrous membrane showed highly specific adsorption of Plg due to the lysine ligand of the thin hydrogel layer on the surface. Importantly, this approach is facile and versatile for different substrates.3. Based on coaxial electrospinning method, we successfully fabricated core-shell nanofibers with cellulose acetate as shell and t-PA as core. TEM analysis confirmed that t-PA was located in the inner layer of the fibers. The results of Bradford test indicated that t-PA released from coaxial electrospun fibrous mats showed stable and sustained release behavior.更多还原