A Localizable, Biological-based System for the Delivery of Bioactive IGF-1 Utilizing Microencapsulated Genetically Modified Human Fibroblasts

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 10⁶ 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 10⁶ 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.