Local delivery of basic fibroblast growth factor (bFGF) using adsorbed silyl-heparin, benzyl-bis(dimethylsilylmethyl)oxycarbamoyl-heparin.
A growth factor delivery system was developed that is based on the use of silyl-heparin, a chemically modified analogue of heparin. The silyl-heparin was adsorbed onto surfaces by hydrophobic interaction via the prosthetic unit and can then be used as a solid-phase adsorbent for bFGF. All the coating steps were performed by adsorption, a process that allowed preparation of surfaces by immersion or "dip-coating". In this study a series of silyl-heparins were synthesized and each of the analogues found to function similar to unmodified heparin relative to their binding of antithrombin III and also the binding of bFGF. The silyl-heparins were found to be adsorbed onto a wide variety of substrates including polystyrene and lactide:glycolide copolymer. Enzyme-linked immumosorbant assay (ELISA) was used to establish that bFGF was readily bound to surface adsorbed silyl-heparin, and that the amount bound was directly related to amount offered for binding. Once adsorbed the silyl-heparin/FGF was able to induce capillary tube formation of endothelial cells and to increase the growth of endothelial cells. When coated onto suture material and implanted in muscle, the FGF/silyl-heparin coating caused an increased density of mesenchymal cells in the area of the implant. This coating method could prove to be useful in a number of tissue engineering applications for the local delivery of FGF and other growth factors.
Zamora
Paul O
PO
Biosurface Engineering Technologies, Inc., 387 Technology Drive, College Park, Maryland 20742-3371, USA. pzamora@biosetinc.com
Tsang
Ray
R
Peña
Louis A
LA
Osaki
Shigemasa
S
Som
Prantika
P
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis; D016503:Drug Delivery Systems / Q000379:methods*; D004730:Endothelium, Vascular / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006493:Heparin / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D020007:Implants, Experimental; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D012821:Silanes / Q000737:chemistry*; D013537:Sutures; D014945:Wound Healing / Q000187:drug effects
D020099:Coated Materials, Biocompatible; D012821:Silanes; D016222:Fibroblast Growth Factor 2; D006493:Heparin