Controlled and modulated release of basic fibroblast growth factor.
Basic fibroblast growth factor has multivariate effects in stimulating cell growth and the processes that surround tissue repair. Pathophysiologic studies have been hampered by the stability of the compound. Though very potent, basic fibroblast growth factor is rapidly degraded when injected or ingested. Controlled release of basic fibroblast growth factor would allow for examination of the chronic effects of this compound. Conventional matrix polymer-based release devices were fabricated and basic fibroblast growth factor released in a sustained fashion, but 99% of basic fibroblast growth factor mitogenic activity was lost. The source of these losses was identified and preventative measures examined. Preservation and stabilization of basic fibroblast growth factor was accomplished by binding the factor to heparin-Sepharose beads. This permitted prolonged storage, repeated handling, and the encapsulation of basic fibroblast growth factor within a microspherical controlled-release device using a naturally occurring polymer material, alginate. Encapsulation was accomplished with 77% efficiency and 87.5 +/- 12% of the basic fibroblast growth factor was released in a biologically active form. Release activation and regulation was achieved when cleavage of the basic fibroblast growth factor-heparin bonds was enhanced (e.g. by enzymatic bond cleavage with heparinase). Kinetic profiles were identified for a variety of experimental conditions and the effects of the controlled release of basic fibroblast growth factor on BALBc/3T3 fibroblasts examined.
Edelman
E R
ER
Biomedical Engineering Center, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139.
Mathiowitz
E
E
Langer
R
R
Klagsbrun
M
M
D000464:Alginates; D000818:Animals; D001672:Biocompatible Materials; D002214:Capsules; D002460:Cell Line; D003692:Delayed-Action Preparations; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D005347:Fibroblasts / Q000187:drug effects; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D011145:Polyvinyls; D011489:Protein Denaturation; D012685:Sepharose / Q000031:analogs & derivatives
D000464:Alginates; D001672:Biocompatible Materials; D002214:Capsules; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D011145:Polyvinyls; C037405:heparin-sepharose; D016222:Fibroblast Growth Factor 2; C016438:ethylenevinylacetate copolymer; D020723:Glucuronic Acid; D012685:Sepharose