Fibrin-based biomaterials to deliver human growth factors

Summary

Fibrin-based biomaterial preparations can be used as provisional growth matrices for cells important in tissue repair during wound healing in vivo. Their efficacy can be enhanced by including bioactive agents that promote specific cellular responses. This study examined the controlled delivery of the angiogenic growth factors bFGF, VEGF₁₆₅, and VEGF₁₂₁ using biomatrix preparations prepared from Fibrin Sealant product components. The growth factors were added prior to formation of the Fibrin Sealant clots, and the release kinetics of the proteins from the clots measured. The results indicated that the proteins were released from the clots more slowly in the order bFGF << VEGF₁₆₅ < VEGF₁₂₁. The biologic activity of the growth factors delivered from Fibrin Sealant clots was established by assaying growth stimulation of human microvascular endothelial cells (HMVEC) and angiogenesis in the chicken embryo chorioallantoic membrane (CAM) model of neovascularization. In the latter assay, clots containing bFGF, VEGF₁₆₅, or V EGF₁₂₁ all displayed angiogenic activity. However, delivery of either bFGF, VEGF₁₆₅, or VEGF₁₂₁ alone resulted in a significant percentage of clots becoming filled with blood, indicating that the newly developing vessels invading the clots were leaky and immature. In contrast, this hemorrhaging behavior did not occur with delivery of combinations, e.g., (VEGF₁₆₅ + VEGF₁₂₁) or (VEGF₁₆₅ + bFGF), indicating that the vessels were more mature than those produced in response to single growth factors. Thus, delivering a combination of growth factors constituted an improvement over the delivery of individual growth factors for enhancing neovascularization.

Part of this research was presented at the joint meetings of the 16^th International Congress of the International Society of Fibrinolysis and Proteolysis and the 17^th International Fibrinogen Workshop of the International Fibrinogen Research Society held in Munich, Germany.

Keywords

Fibrin(ogen) - fibrin sealant - growth factors - angiogenesis - wound healing

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