Cytotoxicity of Cyanoacrylate-Based Tissue Adhesives and Short-Term Preclinical In Vivo Biocompatibility in Abdominal Hernia Repair

PLoS One. 2016 Jun 20;11(6):e0157920. doi: 10.1371/journal.pone.0157920. eCollection 2016.

Abstract

Background: Cyanoacrylate(CA)-based tissue adhesives, although not widely used, are a feasible option to fix a mesh during abdominal hernia repair, due to its fast action and great bond strength. Their main disadvantage, toxicity, can be mitigated by increasing the length of their alkyl chain. The objective was to assess the in vitro cytotoxicity and in vivo biocompatibility in hernia repair of CAs currently used in clinical practice (Glubran(n-butyl) and Ifabond(n-hexyl)) and a longer-chain CA (OCA(n-octyl)), that has never been used in the medical field.

Methods: Formaldehyde release and cytotoxicity of unpolymerized(UCAs) and polymerized CAs(PCAs) were evaluated by macroscopic visual assessment, flow cytometry and Alamar Blue assays. In the preclinical evaluation, partial defects were created in the rabbit abdominal wall and repaired by fixing polypropylene prostheses using the CAs. At 14 days post-surgery, animals were euthanized for morphology, macrophage response and cell damage analyses.

Results: Formaldehyde release was lower as the molecular weight of the monomer increased. The longest side-chain CA(OCA) showed the highest cytotoxicity in the UCA condition. However, after polymerization, was the one that showed better behavior on most occasions. In vivo, all CAs promoted optimal mesh fixation without displacements or detachments. Seroma was evident with the use of Glubran, (four of six animals: 4/6) and Ifabond (2/6), but it was reduced with the use of OCA (1/6). Significantly greater macrophage responses were observed in groups where Glubran and Ifabond were used vs. sutures and OCA. TUNEL-positive cells were significantly higher in the Glubran and OCA groups vs. the suture group.

Conclusions: Although mild formaldehyde release occurred, OCA was the most cytotoxic during polymerization but the least once cured. The CAs promoted proper mesh fixation and have potential to replace traditional suturing techniques in hernia repair; the CAs exhibited good tissue integration and effective short-term biocompatibility, with the slightest seroma and macrophage response induced by OCA.

MeSH terms

  • Animals
  • Biocompatible Materials / pharmacology*
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cyanoacrylates / toxicity*
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Epithelium / pathology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Flow Cytometry
  • Formaldehyde / toxicity
  • Hernia, Abdominal / pathology*
  • Herniorrhaphy*
  • In Situ Nick-End Labeling
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Rabbits
  • Tissue Adhesives / toxicity*

Substances

  • Biocompatible Materials
  • Cyanoacrylates
  • Tissue Adhesives
  • Formaldehyde

Grants and funding

The study was supported by Grant SAF2014-55022-P from Ministerio de Economía y Competitividad, Spain.