control growth factor release using a self-assembled [polycation∶heparin] complex使用自组装生长因子控制释放[聚阳离子∶肝素)复杂.pdf

Control Growth Factor Release Using a Self-Assembled [polycation:heparin] Complex Blaine J. Zern¤a, Hunghao Chu¤b, Yadong Wang*¤b Wallace H. Coulter Department of Biomedical Engineering, School of Chemistry and Biochemistry, and Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia, United States of America Abstract The importance of growth factors has been recognized for over five decades; however their utilization in medicine has yet to be fully realized. This is because free growth factors have short half-lives in plasma, making direct injection inefficient. Many growth factors are anchored and protected by sulfated glycosaminoglycans in the body. We set out to explore the use of heparin, a well-characterized sulfated glycosaminoglycan, for the controlled release of fibroblast growth factor-2 (FGF-2). Heparin binds a multitude of growth factors and maintains their bioactivity for an extended period of time. We used a biocompatible polycation to precipitate out the [heparin:FGF-2] complex from neutral buffer to form a release matrix. We can control the release rate of FGF-2 from the resultant matrix by altering the molecular weight of the polycation. The FGF-2 released from the delivery complex maintained its bioactivity and initiated cellular responses that were at least as potent as fresh bolus FGF-2 and fresh heparin stabilized FGF-2. This new delivery platform is not limited to FGF-2 but applicable to the large family of heparin-binding growth factors. Citation: Zern BJ, Chu H, Wang Y (2010) Control Growth Factor Release Using a Self-Assembled [polycation:heparin] Complex. PLoS ONE 5(6): e11017. doi:10.1371/journal.pone.0011017 Editor: Shuguang Zhang, Massachusetts Institute of Technology, United States of America Received January 11, 2010; Accepted May 17, 2010; Published June 8, 2010 Co