Controlling the biointerface of electrospun mats for clot lysis: an engineered tissue plasminogen activator link to a lysine-functionalized surface

Abstract

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.