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Polymeric system for dual growth factor delivery

Nature Biotechnology volume 19, pages 1029–1034 (2001)Cite this article

Abstract

The development of tissues and organs is typically driven by the action of a number of growth factors. However, efforts to regenerate tissues (e.g., bone, blood vessels) typically rely on the delivery of single factors, and this may partially explain the limited clinical utility of many current approaches. One constraint on delivering appropriate combinations of factors is a lack of delivery vehicles that allow for a localized and controlled delivery of more than a single factor. We report a new polymeric system that allows for the tissue-specific delivery of two or more growth factors, with controlled dose and rate of delivery. The utility of this system was investigated in the context of therapeutic angiogenesis. We now demonstrate that dual delivery of vascular endothelial growth factor (VEGF)-165 and platelet-derived growth factor (PDGF)-BB, each with distinct kinetics, from a single, structural polymer scaffold results in the rapid formation of a mature vascular network. This is the first report of a vehicle capable of delivery of multiple angiogenic factors with distinct kinetics, and these results clearly indicate the importance of multiple growth factor action in tissue regeneration and engineering.

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Figure 1: Schematic of scaffold fabrication process and growth factor release kinetics.
Figure 2: Bolus delivery is not sufficient for stable vessel formation.
Figure 3: Sustained, dual delivery of VEGF and PDGF rapidly forms dense vasculature.
Figure 4: Dual delivery of VEGF and PDGF induces mural cell association.
Figure 5: Dual delivery of VEGF and PDGF induces formation of larger vessels.
Figure 6: Angiogenesis is induced in non-obese diabetic (NOD) mice subjected to femoral ligation surgery.

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Acknowledgements

The authors acknowledge the National Institute of Dental and Craniofacial Research for financial support: R01 DE 13033 (D.J.M.), T32 DE 07057 (T.P.R.), T32 GM08353 (A.B.E.), and the Whitaker Foundation for a graduate student fellowship (M.C.P.).

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Michigan, Ann Arbor, 48109, MI

    Thomas P. Richardson, Martin C. Peters, Alessandra B. Ennett & David J. Mooney

  2. Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, 48109, MI

    Thomas P. Richardson & David J. Mooney

  3. Department of Chemical Engineering, University of Michigan, Ann Arbor, 48109, MI

    David J. Mooney

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  1. Thomas P. Richardson
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Correspondence to David J. Mooney.

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Richardson, T., Peters, M., Ennett, A. et al. Polymeric system for dual growth factor delivery. Nat Biotechnol 19, 1029–1034 (2001). https://doi.org/10.1038/nbt1101-1029

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