Development of novel growth factor fusion proteins with exogenous immobilization domains for cellularly controlled drug delivery

摘要

The objective of this research was to develop a novel method for the delivery of growth factor proteins from fibrin matrices. Nerve growth factor (NGF) fusion proteins containing an exogenous transglutaminase substrate at the N-terminus of the protein were made recombinantly by E. coli. The NGF fusion proteins were covalently immobilized within fibrin matrices during coagulation by the transglutaminase Factor XIIIa, in a maner similar to that used previously to immobilize short peptides (1). The NGF fusion proteins also contained a plasmin substrate between the transglutaminase substrate and the native NGF domain. The plasmin substrate allows for the release of NGF (in a form almost identical to the native sequence) by plasmin degradation. Because the activation of plasminogen to plasmin is tightly regulated by cellular processes, the release of NGF from fibrin matrices occurs in an active manner dependnet on the location and activity of cells within the matrix, rather than in a passive, diffusion-based manner.