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

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 epsilon-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.