Controlling the biointerface of electrospun mats for clot lysis: an engineered tissue plasminogen activator link to a lysine-functionalized surface
Controlling the biointerface of electrospun mats for clot lysis: an engineered tissue plasminogen activator link to a lysine-functionalized surface
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控制电纺垫的生物界面以进行凝块溶解：工程组织纤溶酶原激活剂与赖氨酸功能化表面的连接
DOI：
10.1039/c4tb00488d
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发表时间：
2014
影响因子：
7
通讯作者：
Chen Hong
中科院分区：
文献类型：
--
作者：
Liu Wei;Wu Zhaoqiang;Wang Yanyun;Tang Zengchao;Du Jun;Yuan Lin;Li Dan;Chen Hong
控制利用身体的天然纤维蛋白溶解或凝块溶解能力的生物材料的界面对于防止植入的生物材料上的凝块形成是有吸引力的。在这里，我们设计了生物聚合物电纺纤维垫与组织纤溶酶原激活剂（t-PA）的丝氨酸蛋白酶的界面，旨在模拟身体的纤溶功能。该方法基于聚乙烯醇（PVA）和赖氨酸配体修饰的PVA（PVA-Lys）的一步法静电纺丝水溶液，其中赖氨酸配体的ε-氨基和羧基是游离的。这些静电纺丝毡显示出良好的抵抗纤维蛋白原的非特异性蛋白质吸附和良好的生物相容性与L929细胞使用MTT法。赖氨酸功能化表面通过t-PA与赖氨酸配体的分子识别促进了t-PA的高度特异性束缚。此外，t-PA锚定到PVA/PVA-Lys垫可以很容易地释放纤溶酶原置换时，暴露于血浆，并可以有效地溶解在体外血浆测定中形成的凝块。特别地，在静电纺丝过程中，通过简单地改变PVA和PVA-Lys的共混比，可以容易地调节拴系在垫上的t-PA的量。总的来说，考虑到简单性、可控性和生物相容性的优点，这种方法有望用于构建血液接触装置的生物界面。
Controlling the interface of biomaterials that take advantage of the natural fibrinolytic or clot-dissolving capacity of the body is attractive for preventing clot formation on an implanted biomaterial. Here, we engineer the interface of a biopolymer electrospun fiber mat with a serine protease of the tissue plasminogen activator (t-PA), aiming to simulate fibrinolytic functions of the body. The method is based on the one-step electrospinning aqueous solution of poly(vinyl alcohol) (PVA) and lysine ligand-modified PVA (PVA–Lys), in which the ε-amino and carboxyl groups of the lysine ligands were free. These 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-functionalized surface through molecular recognition of t-PA to the lysine ligands. Moreover, the t-PA anchorage to the PVA/PVA–Lys mats can be easily released by plasminogen displacement when exposed to plasma, and can efficiently lyse the formed-clot in an in vitro plasma assay. In particular, the quantities of t-PA tethered on the mats could easily be regulated by simply varying the blend ratio of PVA and PVA–Lys in the electrospinning process. Collectively, considering the advantages of simplicity, controllability and biocompatibility, this approach is expected to be useful for the construction of a biointerface for blood-contacting devices.