[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

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.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Langer, R. & Vacanti, J. P. Tissue engineering. Science 260, 920–926 ( 1993).

    Article  ADS  CAS  Google Scholar 

  2. Putnam, A. J. & Mooney, D. J. Tissue engineering using synthetic extracellular matrices. Nature Med. 2, 824 –826 (1996).

    Article  CAS  Google Scholar 

  3. Shea, L. D., Smiley, E., Bonadio, J. & Mooney, D. J. DNA delivery from polymer matrices for tissue engineering. Nature Biotechnol. 17, 551–554 ( 1999).

    Article  CAS  Google Scholar 

  4. Ripamonti, U. & Reddi, A. H. Tissue engineering, morphogenesis, and regeneration of the periodontal tissues by bone morphogenetic proteins. Crit. Rev. Oral Biol. Med. 8, 154– 163 (1997).

    Article  CAS  Google Scholar 

  5. Kim, B.-S., Nikolovski, J., Bonadio, J. & Mooney, D. J. Cyclic mechanical strain regulates the development of engineered smooth muscle tissue. Nature Biotechnol. 17, 979– 983 (1999).

    Article  CAS  Google Scholar 

  6. Niklason, L. E. et al. Functional arteries grown in vitro. Science 284, 489–493 ( 1999).

    Article  ADS  CAS  Google Scholar 

  7. Vlodavsky, I. et al. Extracellular sequestration and release of fibroblast growth factor: a regulatory mechanism? Trends Biochem. Sci. 16, 268–271 (1991).

    Article  CAS  Google Scholar 

  8. Neufeld, G., Cohen, T., Gengrinovitch, S. & Poltorak, Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13, 9–22 ( 1999).

    Article  CAS  Google Scholar 

  9. Baldwin, S. P. & Saltzman, W. M. Materials for protein delivery in tissue engineering. Adv. Drug Delivery Rev. 33, 71–86 (1998).

    Article  CAS  Google Scholar 

  10. Jen, A. C., Wake, M. C. & Mikos, A. G. Hydrogels for cell immobilization. Biotechnol. Bioeng. 50, 357–364 ( 1996).

    Article  CAS  Google Scholar 

  11. Plate, K. H., Breiser, G., Weich, H. A. & Risau, W. Vascular endothelial growth factor is a potential tumor angiogenesis factor in vivo. Nature 359, 845– 848 (1992).

    ADS  CAS  PubMed  Google Scholar 

  12. Chicurel, M. E., Chen, C. S. & Ingber, D. E. Cellular control lies in the balance of forces. Curr. Opin. Cell Biol. 10, 232–239 (1998).

    Article  CAS  Google Scholar 

  13. Williams, B. Mechanical influences on vascular smooth muscle cell function. J. Hypertension 16, 1921–1929 (1998).

    Article  CAS  Google Scholar 

  14. Langer, R. Drug delivery and targeting. Nature 392 (suppl.), 5–10 (1998).

    CAS  Google Scholar 

  15. Wang, C., Stewart, R. J. & Kopecek, J. Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains. Nature 397, 417–420 (1999).

    Article  ADS  CAS  Google Scholar 

  16. Chen, G. & Hoffman, A. S. Graft copolymers that exhibit temperature-induced phase transition over a wide range of pH. Nature 373, 49–52 ( 1995).

    Article  ADS  CAS  Google Scholar 

  17. Mitragorti, S., Blankschtein, D. & Langer, R. Ultrasound-mediated transdermal protein delivery. Science 269, 850–853 ( 1995).

    Article  ADS  Google Scholar 

  18. Kwon, I. C., Bae, Y. H. & Kim, S. W. Electrically erodible polymer gel for controlled release of drugs. Nature 354, 291– 293 (1991).

    Article  ADS  CAS  Google Scholar 

  19. Edelman, E., Brown, L. & Langer, R. In vitro and in vivo kinetics of regulated drug release from polymer matrices by oscillating magnetic fields. J. Biomed. Mater. Res. 21, 339–353 (1987).

    Article  CAS  Google Scholar 

  20. Nör, J. E., Christensen, J., Mooney, D. J. & Polverini, P. J. Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of BCL-2 expression. Am. J. Pathol. 152, 375– 384 (1999).

    Article  Google Scholar 

Download references

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.

Author information

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

Authors
  1. Kuen Yong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin C. Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenneth W. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David J. Mooney
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David J. Mooney.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/35050141

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing