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Controlled growth factor release from synthetic extracellular matrices

Nature volume 408, pages 998–1000 (2000)Cite this article

Abstract

Polymeric matrices can be used to grow new tissues and organs1,2, and the delivery of growth factors from these matrices is one method to regenerate tissues3,4. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels5,6, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.

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Figure 1: In vitro release profile of VEGF from alginate hydrogels under mechanical stimulation.
Figure 2: In vivo response to VEGF released from alginate hydrogels under mechanical stimulation.
Figure 3: Quantitative analysis of granulation tissue formed in SCID mice.
Figure 4: In vivo response to VEGF-loaded hydrogels implanted into femoral artery ligation site of NOD mice.

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Acknowledgements

We thank the National Institutes of Health for financial support of this research. M.C.P. acknowledges the Whitaker Foundation for a graduate fellowship.

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Authors and Affiliations

  1. Departments of Biologic & Materials Sciences, Ann Arbor, 48109 , Michigan, USA

    Kuen Yong Lee, Kenneth W. Anderson & David J. Mooney

  2. Chemical Engineering, Ann Arbor, 48109 , Michigan, USA

    Kuen Yong Lee & David J. Mooney

  3. Biomedical Engineering, Ann Arbor, 48109 , Michigan, USA

    Kuen Yong Lee, Martin C. Peters & David J. Mooney

  4. Otolaryngology–Head & Neck Surgery, University of Michigan, Ann Arbor, 48109 , Michigan, USA

    Kenneth W. Anderson

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  1. Kuen Yong Lee
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  2. Martin C. Peters
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  4. David J. Mooney
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Correspondence to David J. Mooney.

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Lee, K., Peters, M., Anderson, K. et al. Controlled growth factor release from synthetic extracellular matrices . Nature 408, 998–1000 (2000). https://doi.org/10.1038/35050141

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