**4. Fibrin**

Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed from fibrinogen by the protease thrombin, and is then polymerised to form a hemostatic plug or clot (in conjunction with platelets) over a wound site [30]. The clot fibrin can be naturally degraded by proteolytic enzymes from the fibrinolytic system, such as plasmin [31,32]. *In vivo*, fibrin(ogen) plays an important role in hemostasis, inflammation, signal transduction, platelet activation, wound healing, osteoinductive and angiogenesis [33-36]. The food and drug administration (FDA) in American has approved commercially made fibrin sealants in 1998 [37].

During the last decade, autologous fibrin-based matrices have demonstrated great potential as being used as tissue engineered replacements, such as heart valves [38-40], cartilages [41], and blood vessels [42]. Immunohistochemistry and ECM assay demonstrated that the fibrin scaf‐ folds can be completely absorbed *in vivo* in about 3 months with low granulomatous inflamma‐ tion (Figure 3) [43-46]. Farhat and coworkers have evaluated whether a fibrin glue spray technique enhances cell seeded acellular matrix (ACM) repopulation in a porcine bladder mod‐ el. The *in vivo* central fibrosis results indicated that while fibrin glue enhanced cellular organiza‐ tion on ACM *in vitro*, factors supporting seeded cell survival are lacking [47].

On the other hand, spatio-temporal controlled delivery of bioactive molecules within fibrin has been expanded rapidly. Various states of fibrin, such as scaffold, sheets, microparticles and fibrin-coated drug particles have been used as drug delivery systems [48,49]. Growth factors, such as vascular endothelial growth factor (VEGF) and transforming growth factorβ (TGF-β) can easily bind to the fibrin molecules and be controlled released subsequently by diffusion [50-56]. In the future, autologous fibrin may play an important role in customized clinical applications, such as anti-immune drug delivery systems and human tissue/organ constructions to avoid any negative host reactions [57].
