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The nucleic acid scavenger polyamidoamine third-generation dendrimer inhibits fibroblast activation and granulation tissue contraction.

Publication ,  Journal Article
Holl, EK; Bond, JE; Selim, MA; Ehanire, T; Sullenger, B; Levinson, H
Published in: Plast Reconstr Surg
September 2014

BACKGROUND: Pathologic cutaneous scarring affects over 40 million people worldwide and costs billions of dollars annually. Understanding mechanisms of fibroblast activation and granulation tissue contraction is the first step toward preventing pathologic scarring. The authors hypothesize that nucleic acids increase fibroblast activation and cause granulation tissue contraction and that sequestration of nucleic acids by application of a nucleic acid scavenger dendrimer, polyamidoamine third-generation dendrimer, will decrease pathologic scarring. METHODS: In vitro experiments were performed to assess the effect of nucleic acids on pathologic scar-associated fibroblast activity. The effect of nucleic acids on cytokine production and migration on mouse fibroblasts was evaluated. Immunofluorescence microscopy was used to determine the effect of nucleic acids on the differentiation of human primary fibroblasts into myofibroblasts. Using a murine model, the effect of polyamidoamine third-generation dendrimer on granulation tissue contraction was evaluated by gross and histologic parameters. RESULTS: Mouse fibroblasts stimulated with nucleic acids had increased cytokine production (i.e., transforming growth factor-β, monocyte chemotactic protein 1, interleukin-10, tumor necrosis factor-α, and interferon-γ), migration, and differentiation into myofibroblasts. Polyamidoamine third-generation dendrimer blocked cytokine production, migration, and differentiation into myofibroblasts. Using a murine model of granulation tissue contraction, polyamidoamine third-generation dendrimer decreased wound contraction and angiogenesis. Collagen deposition in polyamidoamine third-generation dendrimer-treated tissues was aligned more randomly and whorl-like compared with control tissue. CONCLUSIONS: The data demonstrate that nucleic acid-stimulated fibroblast activation and granulation tissue contraction are blocked by polyamidoamine third-generation dendrimer. Sequestration of pathogen-associated molecular patterns may be an approach for preventing pathologic scarring.

Duke Scholars

Published In

Plast Reconstr Surg

DOI

EISSN

1529-4242

Publication Date

September 2014

Volume

134

Issue

3

Start / End Page

420e / 433e

Location

United States

Related Subject Headings

  • Wound Healing
  • Toll-Like Receptors
  • Surgery
  • Signal Transduction
  • Real-Time Polymerase Chain Reaction
  • Polyamines
  • Nucleic Acids
  • Microscopy, Fluorescence
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Holl, E. K., Bond, J. E., Selim, M. A., Ehanire, T., Sullenger, B., & Levinson, H. (2014). The nucleic acid scavenger polyamidoamine third-generation dendrimer inhibits fibroblast activation and granulation tissue contraction. Plast Reconstr Surg, 134(3), 420e-433e. https://doi.org/10.1097/PRS.0000000000000471
Holl, Eda K., Jennifer E. Bond, Maria A. Selim, Tosan Ehanire, Bruce Sullenger, and Howard Levinson. “The nucleic acid scavenger polyamidoamine third-generation dendrimer inhibits fibroblast activation and granulation tissue contraction.Plast Reconstr Surg 134, no. 3 (September 2014): 420e-433e. https://doi.org/10.1097/PRS.0000000000000471.
Holl EK, Bond JE, Selim MA, Ehanire T, Sullenger B, Levinson H. The nucleic acid scavenger polyamidoamine third-generation dendrimer inhibits fibroblast activation and granulation tissue contraction. Plast Reconstr Surg. 2014 Sep;134(3):420e-433e.
Holl, Eda K., et al. “The nucleic acid scavenger polyamidoamine third-generation dendrimer inhibits fibroblast activation and granulation tissue contraction.Plast Reconstr Surg, vol. 134, no. 3, Sept. 2014, pp. 420e-433e. Pubmed, doi:10.1097/PRS.0000000000000471.
Holl EK, Bond JE, Selim MA, Ehanire T, Sullenger B, Levinson H. The nucleic acid scavenger polyamidoamine third-generation dendrimer inhibits fibroblast activation and granulation tissue contraction. Plast Reconstr Surg. 2014 Sep;134(3):420e-433e.

Published In

Plast Reconstr Surg

DOI

EISSN

1529-4242

Publication Date

September 2014

Volume

134

Issue

3

Start / End Page

420e / 433e

Location

United States

Related Subject Headings

  • Wound Healing
  • Toll-Like Receptors
  • Surgery
  • Signal Transduction
  • Real-Time Polymerase Chain Reaction
  • Polyamines
  • Nucleic Acids
  • Microscopy, Fluorescence
  • Mice, Inbred C57BL
  • Mice