TG-APROTININ FUSION PROTEINS AND MATRICES THEREOF

摘要

Fusion proteins containing a first domain and a second domain, where the first domain contains a crosslinkable substrate domain and the second domain contains a fibrinolysis inhibitor, are provided. In a preferred embodiment, the fibrinolysis inhibitor is a protease inhibitor, preferably, aprotinin. The fusion protein optionally contains a degradable site between the fist domain and the second domain. In a preferred embodiment, the crosslinkable substrate domain is a transglutaminase substrate domain, more preferably a Factor XIIIa substrate domain. Also provided is a method for decreasing the degradation of a fibrin matrix, and supplemented fibrin matrices with reduced degradation rates. The method includes covalently crossHnking a fusion protein containing a fibrinolysis inhibitor to the matrix. The supplemented fibrin matrices contain lower concentrations of a fibrinolysis inhibitor covalently bound to the matrix, compared to the concentration of unbound fibrinolysis inhibitor required to achieve the same reduction in degradation of the fibrin matrix.