Open AccessA Localizable, Biological-based System for the Delivery of Bioactive IGF-1 Utilizing Microencapsulated Genetically Modified Human Fibroblasts
Author(s) -
Richa Patel,
Tecla M Temu,
Laura Jeanbart,
Jeffrey R. Morgan,
Michael J. Lysaght
Publication year - 2009
Publication title -
asaio journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.961
H-Index - 66
eISSN - 1538-943X
pISSN - 1058-2916
DOI - 10.1097/mat.0b013e31819b0365
Subject(s) - recombinant dna , growth factor , transfection , tissue engineering , genetically modified organism , gene delivery , biological activity , microbiology and biotechnology , biology , chemistry , biomedical engineering , gene , in vitro , biochemistry , receptor , medicine , genetics
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.