Fibrin-based biomaterials to deliver human growth factors.
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, VEGF(165), and VEGF(121) 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 << VEGF(165) < VEGF(121). 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, VEGF(165), or VEGF(121) all displayed angiogenic activity. However, delivery of either bFGF, VEGF(165), or VEGF(121) 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., (VEGF(165) + VEGF(121)) or (VEGF(165) + 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.
Wong
Catalina
C
BioSurgery Group, BioScience R&D, Baxter Healthcare Corp 1720 Flower Ave., Duarte, CA 91010, USA.
Inman
Elisabeth
E
Spaethe
Reiner
R
Helgerson
Sam
S
D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D000818:Animals; D001672:Biocompatible Materials; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects; D016503:Drug Delivery Systems; D016228:Endothelial Growth Factors / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005337:Fibrin; D015718:Fibrin Tissue Adhesive; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage; D006133:Growth Substances / Q000008:administration & dosage*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage; D008222:Lymphokines / Q000008:administration & dosage; D008422:Materials Testing; D018919:Neovascularization, Physiologic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014945:Wound Healing / Q000187:drug effects
D001672:Biocompatible Materials; D016228:Endothelial Growth Factors; D015718:Fibrin Tissue Adhesive; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D005337:Fibrin