title: A localizable, biological-based system for the delivery of bioactive IGF-1 utilizing microencapsulated genetically modified human fibroblasts.
abstract: Insulin-like growth factor 1 (IGF-1) is a potent mitogen and differentiation factor with particular relevance to orthopedic tissue engineering. A biologically based Ca2+-alginate microcapsule vehicle, utilizing genetically modified primary normal human fibroblasts (NHFs), was developed and characterized for localized synthesis and delivery of human IGF-1 (hIGF-1). Normal human fibroblasts were transfected to overexpress the hIGF-1 gene, leading to cells that expressed 4 ng of hIGF-1 per 10(6) cells per 24 hours. Encapsulation within alginate led to a six-fold enhancement in the generation and release of hIGF-1 to 22 ng of hIGF-1 per 10(6) cells per 24 hours. Release was constitutive, predictable, and exhibited highly repeatable first-order kinetics with no initial burst. Released growth factor was biologically active and exhibited a proliferative effect comparable to commercially available recombinant hIGF-1. The magnitude of hIGF-1 release met the requirements of orthopedic tissue generation, and this approach is considered an attractive alternative to other proposed methods of growth factor delivery.
authors.affiliation: Center for Biomedical Engineering, Brown University, Providence, Rhode Island 02912, USA. roshni_patel@brown.edu
authors.forename: Roshni S
authors.initials: RS
authors.lastname: Patel
authors.forename: Tecla M
authors.initials: TM
authors.lastname: Temu
authors.forename: Laura
authors.initials: L
authors.lastname: Jeanbart
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Morgan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lysaght
mesh_terms: D000464:Alginates; D001672:Biocompatible Materials; D049109:Cell Proliferation; D002470:Cell Survival; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D005347:Fibroblasts / Q000378:metabolism*; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D007334:Insulin-Like Growth Factor I; D020723:Glucuronic Acid