Effects of mast cell modulation on early host response to implanted synthetic meshes

Sean Orenstein, E. R. Saberski, U. Klueh, D. L. Kreutzer, Y. W. Novitsky

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Introduction: Mast cells (MCs) and their products (e.g., histamine, serotonin, heparin, prostaglandins, cytokines, etc.) play key roles in controlling local inflammation, wound healing, and foreign body reactions in vivo. Investigation of the role of MCs in mediating local tissue responses to synthetic hernia meshes has been very limited to date. We aimed to determine the effects of MCs/MC products in mice undergoing synthetic mesh implantation. Materials and methods: Circular samples (5 mm) of heavyweight microporous polypropylene (Trelex®), midweight microporous polypropylene (ProLite™), lightweight macroporous polypropylene with poliglecaprone (Ultrapro™), and 3-dimensional macroporous polyester (Parietex™) meshes were implanted subcutaneously in C57BL/6 J mice with and without cromolyn (MC stabilizer/suppressant) treatment (50 mg/kg, daily IP). Two weeks post-implantation, all meshes were explanted and evaluated histologically using H&E and trichrome stains. Results: Chronic inflammation was focused around individual mesh fibers; inter-fiber inflammation and fibrosis diminished as mesh porosity increased. MC accumulation was seen at the periphery of inflammatory reactions, and in association with mesh-induced fibrosis and neovascularization. Cromolyn treatment resulted in significantly decreased fibrotic responses to all four meshes and reduced inflammation induced by Trelex®, ProLite™, and Parietex™ meshes but not Ultrapro™. Conclusion: We demonstrated that MCs play important roles in mesh-induced host tissue reactions. Blocking MC degranulation decreased early inflammation and fibrosis induced by most synthetic meshes in this study. Further evaluation and understanding of the role of MCs in mesh-induced tissue reactions will provide new therapeutic approaches to enhance the biocompatibility of surgical meshes and ultimately improve clinical outcomes in patients undergoing hernia repair with synthetic biomaterials.

Original languageEnglish (US)
Pages (from-to)511-516
Number of pages6
JournalHernia
Volume14
Issue number5
DOIs
StatePublished - Oct 2010
Externally publishedYes

Fingerprint

Mast Cells
Polypropylenes
Inflammation
Cromolyn Sodium
Fibrosis
Surgical Mesh
Foreign-Body Reaction
Cell Degranulation
Polyesters
Herniorrhaphy
Porosity
Biocompatible Materials
Hernia
Wound Healing
Histamine
Prostaglandins
Heparin
Serotonin
Therapeutics
Cytokines

Keywords

  • Biomaterial
  • Cromolyn
  • Foreign body reaction
  • Hernia
  • In vivo
  • Inflammation
  • Mast cell
  • Mesh
  • Mouse
  • Synthetic
  • Wound healing

ASJC Scopus subject areas

  • Surgery

Cite this

Effects of mast cell modulation on early host response to implanted synthetic meshes. / Orenstein, Sean; Saberski, E. R.; Klueh, U.; Kreutzer, D. L.; Novitsky, Y. W.

In: Hernia, Vol. 14, No. 5, 10.2010, p. 511-516.

Research output: Contribution to journalArticle

Orenstein, Sean ; Saberski, E. R. ; Klueh, U. ; Kreutzer, D. L. ; Novitsky, Y. W. / Effects of mast cell modulation on early host response to implanted synthetic meshes. In: Hernia. 2010 ; Vol. 14, No. 5. pp. 511-516.
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AU - Orenstein, Sean

AU - Saberski, E. R.

AU - Klueh, U.

AU - Kreutzer, D. L.

AU - Novitsky, Y. W.

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AB - Introduction: Mast cells (MCs) and their products (e.g., histamine, serotonin, heparin, prostaglandins, cytokines, etc.) play key roles in controlling local inflammation, wound healing, and foreign body reactions in vivo. Investigation of the role of MCs in mediating local tissue responses to synthetic hernia meshes has been very limited to date. We aimed to determine the effects of MCs/MC products in mice undergoing synthetic mesh implantation. Materials and methods: Circular samples (5 mm) of heavyweight microporous polypropylene (Trelex®), midweight microporous polypropylene (ProLite™), lightweight macroporous polypropylene with poliglecaprone (Ultrapro™), and 3-dimensional macroporous polyester (Parietex™) meshes were implanted subcutaneously in C57BL/6 J mice with and without cromolyn (MC stabilizer/suppressant) treatment (50 mg/kg, daily IP). Two weeks post-implantation, all meshes were explanted and evaluated histologically using H&E and trichrome stains. Results: Chronic inflammation was focused around individual mesh fibers; inter-fiber inflammation and fibrosis diminished as mesh porosity increased. MC accumulation was seen at the periphery of inflammatory reactions, and in association with mesh-induced fibrosis and neovascularization. Cromolyn treatment resulted in significantly decreased fibrotic responses to all four meshes and reduced inflammation induced by Trelex®, ProLite™, and Parietex™ meshes but not Ultrapro™. Conclusion: We demonstrated that MCs play important roles in mesh-induced host tissue reactions. Blocking MC degranulation decreased early inflammation and fibrosis induced by most synthetic meshes in this study. Further evaluation and understanding of the role of MCs in mesh-induced tissue reactions will provide new therapeutic approaches to enhance the biocompatibility of surgical meshes and ultimately improve clinical outcomes in patients undergoing hernia repair with synthetic biomaterials.

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KW - Synthetic

KW - Wound healing

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