Preparation And Applications Of Electrospun Mats With Fibrinolytic Function

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.