Cell responses to BMP-2 and IGF-I released with different time-dependent profiles.

Abstract

During wound healing, growth factors are expressed in time-dependent amounts. Constant delivery of biomolecules, however, is often used to influence cell and tissue behavior. In the present studies, a crosslinked gelatin-coating system was used to deliver bone morphogenetic protein 2 (BMP-2) or insulin-like growth factor (IGF-I) to three types of mesenchymal cells with three temporally varying release profiles. The "early" delivery profile released most of the growth factor within the first 2 days. The "pseudo-zero-order" profile approximated constant rate of delivery for about 5 days. The "late" delivery profile released most of the growth factor after about 5 days. Early delivery of IGF-I had the greatest effect on mitogenesis of SaOS-2 human osteosarcoma cells with a secondary effect noted nearly 5 days after delivery was completed. Late delivery of BMP-2 resulted in greatest alkaline phosphatase (AP) activity in mouse pluripotent C3H10T1/2 cells. Rat bone marrow stromal cells (BMCs) responded to all delivery profiles of BMP-2, with the duration of elevated AP activity increasing as the amount of BMP-2 delivered increased. In addition to an early increase in AP activity, late release also stimulated BMCs over a longer portion of the culture period. BMCs responded similarly to SaOS-2 cells when seeded on early IGF-I delivery coatings, increasing AP activity after delivery had ended. Overall, these studies further show the importance of delivery profile, specifically the characteristics of time and concentration, on cell and tissue responses.