Fibrin as a delivery system in wound healing tissue engineering applications

Fibrin is formed in the body upon initiation of the clotting cascade and is produced commercially for use as a tissue sealant and hemostasis device during surgical procedures. Experimentally fibrin is being increasingly used as a vector to deliver growth factors, cells, drugs and genes in tissue engineering applications mimicking aspects of the extra cellular matrix. Growth factors (GFs) are central to wound healing, inducing cell proliferation, migration and differentiation. Attempts have been made to augment wound healing with GFs, however widespread clinical use has been hindered in vivo due to their rapid metabolism within the body. Fibrin hydrogels protect GFs from rapid degradation and the composition of which can be altered to achieve their optimal release. This article reviews the use of fibrin for the delivery of GFs and details the various strategies that have evolved to alter the release rate so as to enhance the regenerative process, including bi-domain peptides, plasmin degradation sequences and heparin incorporation. This paper also reviews other recent advances in this field, such as dual delivery of cells and GF or sequential release of multiple GF.