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.

  • Research Article
  • Published:

DNA delivery from polymer matrices for tissue engineering

Nature Biotechnology volume 17, pages 551–554 (1999)Cite this article

An Erratum to this article was published on 01 August 1999

Abstract

We have proposed engineering tissues by the incorporation and sustained release of plasmids encoding tissue-inductive proteins from polymer matrices. Matrices of poly(lactide-co-glycolide) (PLG) were loaded with plasmid, which was subsequently released over a period ranging from days to a month in vitro. Sustained delivery of plasmid DNA from matrices led to the transfection of large numbers of cells. Furthermore, in vivo delivery of a plasmid encoding platelet-derived growth factor enhanced matrix deposition and blood vessel formation in the developing tissue. This contrasts with direct injection of the plasmid, which did not significantly affect tissue formation. This method of DNA delivery may find utility in tissue engineering and gene therapy applications.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: (A) Cross-sectional view of 75:25 PLG sponge fabricated with the gas foaming procedure and (B) the cumulative release of plasmid DNA from 75:25 (i.v. = 0.2) (●), 85:15 (i.v. = 0.7) (□), and 75:25 (i.v. = 0.7) (░) PLG.
Figure 2: In vitro transfection by plasmid DNA released at different times from the polymer sponge.
Figure 3: Photomicrograph of a cross section of tissue containing polymer matrix loaded with nt β-gal, which was retrieved four weeks after implantation.
Figure 4: In vivo response to release of plasmids encoding for PDGF and control (nt β-gal) at two and four weeks.

Similar content being viewed by others

References

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

    Article  CAS  Google Scholar 

  2. Kim, B.S. & Mooney, D.J. Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol. 16, 224–230 ( 1998).

    Article  CAS  Google Scholar 

  3. Mooney, D.J. et al. Long-term engraftment of hepatocytes transplanted on biodegradable polymer sponges. J. Biomed. Mater. Res. 37, 413–420 (1997).

    Article  CAS  Google Scholar 

  4. Deuel, T.F. in: Principles of tissue engineering (eds Lanza, R.P., Langer, R. & Chick W.L.) 133–150 (Academic, San Diego, 1997).

    Google Scholar 

  5. Langer, R. New methods of drug delivery. Science 249, 1527–1533 (1992).

    Article  Google Scholar 

  6. Jong, Y.S. et al. Controlled release of plasmid DNA. J. Cont. Rel. 47 , 123–134 (1997) [Not In Index Medicus Please Spell Out].

    Article  CAS  Google Scholar 

  7. Labhasetwar, V., Bonadio, J., Goldstein, S., Chen, W. & Levy, R.J. A DNA controlled-release coating for gene transfer: transfection in skeletal and cardiac muscle. J. Pharm. Sci. 87, 1347–1350 (1998).

    Article  CAS  Google Scholar 

  8. Ledley, F.D. Pharmaceutical approach to somatic gene therapy. Pharm. Res. 13, 1595–1614 (1996).

    Article  CAS  Google Scholar 

  9. Giannobile, W.V. Periodontal tissue engineering by growth factors. Bone 19, 23S–37S (1996).

    Article  CAS  Google Scholar 

  10. Harris, L.D., Kim, B.S. & Mooney, D.J. Open pore biodegradable matrices formed with gas foaming. J. Biomed. Mat. Res. 42, 396– 402 (1998).

    Article  CAS  Google Scholar 

  11. Wong, W.H. & Mooney D.J. in Synthetic biodegradable polymer scaffolds (eds Atala, A. & Mooney, D.J.) 51– 82 (Birkhausen, Boston; 1997).

    Book  Google Scholar 

  12. Raines, E.W. & Ross, R. in Biology of platelet-derived growth factor (eds Westermark, B. & Sorg, C.) 74– 114 (Karger, Switzerland; 1993).

    Google Scholar 

  13. Peters, M.C. & Mooney, D.J. in Tissue engineering for therapeutic use 2. (eds Ikada, Y. & Enomoto, S.) 55–65 (Elsevier, Amsterdam; 1998).

    Google Scholar 

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

    Google Scholar 

  15. Hedley, M.L. Curley, J. & Urban, R. Microspheres containing plasmid-encoded antigens elicit cytotoxic T-cell responses. Nat. Med. 4, 365–368 (1998).

    Article  CAS  Google Scholar 

  16. Nor, J.E., Christensen, J., Mooney, D.J. & Polverini, P. VEGF enhances the survival of endothelial cells and sustains angiogenesis by inducing expression of Bcl-2. Am. J. Pathol. 154 , 375–384 (1999).

    Article  CAS  Google Scholar 

  17. Stein, G.S., Lian, J.B., Stein, J.L., Van Wijnen, A.J. & Montecino, M. Transcriptional control of osteoblast growth and differentiation. Physiol. Rev. 76, 593– 629 (1996).

    Article  CAS  Google Scholar 

  18. Fang, J. et al. Stimulation of new bone formation by direct transfer of osteogenic plasmid genes. Proc. Nat. Acad. Sci.USA 93, 5753–5758 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge technical assistance from Jeremy Blum and Elly Liao. Financial support for this work was provided by National Institutes of Health grant 1RO1DE13004, Reprogenesis, and Selective Genetics. L.D.S. was supported by National Institute of Dental Researchtraining grant DE07057.

Author information

Authors and Affiliations

  1. Department of Biologic and Materials Science, University of Michigan, Ann Arbor, 48109-1078, MI

    Lonnie D. Shea & David J. Mooney

  2. Department of Biomedical Engineering, University of Michigan, Ann Arbor, 48109-1078, MI

    Lonnie D. Shea & David J. Mooney

  3. Department of Pathology, University of Michigan, Ann Arbor, 48109-1078, MI

    Elizabeth Smiley & Jeffrey Bonadio

  4. Department of Chemical Engineering, University of Michigan, Ann Arbor, 48109-1078, MI

    David J. Mooney

Authors
  1. Lonnie D. Shea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth Smiley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeffrey Bonadio
    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.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shea, L., Smiley, E., Bonadio, J. et al. DNA delivery from polymer matrices for tissue engineering. Nat Biotechnol 17, 551–554 (1999). https://doi.org/10.1038/9853

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/9853

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