In Vitro Toxicity Test of Ethyl 2-Cyanoacrylate, a Tissue Adhesive Used in Cardiovascular Surgery, by Fibroblast Cell Culture Method


  • Mehmet Kaplan
  • Kemal Baysal



Background: The aim of this study was to evaluate the cytotoxicity of cyanoacrylate polymers (ethyl 2-cyanoacrylate) by an elution test system. In such systems, the material is extracted with a cell culture medium, which is subsequently added onto cultured cells, resulting in an indirect contact between the biomaterial and cells.

Methods: A cell line commonly utilized for cytotoxicity experiments; L929 mouse fibroblasts were used in this study. The effects of extract dilutions on cells were evaluated by two experiments: (a) The cells were suspended and seeded in a medium containing the extract, followed by a short incubation to observe the effects on cell attachment; (b) cells were seeded in a normal medium. Following cell attachment, this was replaced with a medium containing the extract and long-term effects on cell proliferation were measured. The cytotoxicity was quantified using a cell viability assay, well established for use in the evaluation of cell-biomaterial interactions.

Results: These results indicate that, in the test system utilized, a tenfold dilution of the extract results in an ~10% decrease in cells; this increases to between 30% and 45% in a 1:1 dilution. When a large number of cells (3000/well) were used, proliferation of cells overcame the cytotoxic effect and consistent results could not be observed.

Conclusions: In this study, the observed outcomes follow a similar trend on cell attachment and proliferation with acute effects (4 hours incubation) of the extracts on the cells, producing slightly higher toxicity. Our findings are parallel with the literature findings.


Applebaum JS, Zalut T, Applebaum D. 1993. The use of tissue adhesion for traumatic laceration repair in the emergency department. Ann Emerg Med 22:1190-2.nEastman DP, Robicsek F. 1998. Application of cyanoacrylate adhesive (Krazy glue) in critical cardiac injuries. J Heart Valve Dis 7:888-9.nEvans CE, Lees GC, Trail IA. 1999. Cytotoxicity of cyanoacrylate adhesives to cultured tendon cells. J Hand Surgery 24B:6:658-61.nGuo Y, Baysal K, Kang B, Yang LJ, Williamson JR. 1998. J Biol Chem 273:4027.nHorsley WS, Miller JI Jr. 1997. Management of the uncontrollable air leak with cyanoacrylate glue. Ann Thorac Surg 63:1492-3.nBrauer GM, Kumpula JW, Termini DJ, Davidson KM. 1979. Durability of the bond between bone and various 2-cyanoacrylates in an aqueous environment. J Biomed Mater Res 13:593-606.nCiapetti G, Stea S, Cenni E, et al. 1994. Toxicity of cyanoacrylates in vitro using extract dilution assay on cell cultures. Biomaterials 15:92-6.nDe Blanco LP. 1994. Lip suture with isobutyl cyanoacrylate. Endod Dent Traumatol 10:15-8.nCenni E, Ciapetti G, Granchi D, et al. 1999. Established cell lines and primary cultures in testing medical devices in vitro. Toxicol In Vitro 13:801-10.nDemirtas MM, Akcar M, Sarikaya S. 1998. Avoidance of sternal nonunion with cyanoacrylate gluing. Ann Thorac Surg 66:304-6.nDemirtas MM, Cimen S, Ketenci B, Gunay R, Akcar M, Ozler A. 1999. Late follow-up of cyanoacrylate usage in cardiothoracic surgery. Asian Cardiovasc Thorac Ann 7:195-9.nKaplan M, Bozkurt S, Kut MS, Kullu S, Demirtas MM. 2004. Histopathological effects of ethyl 2-cyanoacrylate tissue adhesive following surgical application - An experimental study. Eur J Cardiothorac Surg 25:167-72.nKaplan M, Oral B, Rollas S, Kut MS, Demirtas MM. 2004. Absorption of ethyl 2-cyanoacrylate tissue adhesive. Eur J Drug Metab Pharma-cokinet 29:77-81.nLeahey AB, Gottach JD, Stark WJ. 1993. Clinical experience with N-butyl cyanoacrylate (Nexacryl) tissue adhesive. Ophthalmology 100:173-80.nLeonard F, Kulkarni RK, Nelson J, Brandes G. 1967. Tissue adhesives and hemostasis-inducing compounds: The alkyl cyanoacrylates. J Biomed Mater Res 1:3-9.nMontanaro L, Arciola CR, Cenni E, et al. 2001. Cytotoxicity, blood compatibility and antimicrobial activity of two cyanoacrylate glues for surgical use. Biomaterials 22:59-66.nNishi C, Nakajima N, Ikada Y. 1995. In vitro evaluation of cytotoxicity of diepoxy compounds used for biomaterial modification. J Biomed Mater Res 29:829-34.nThumwaint V, Kedjarune U. 1999. Cytotoxicity of polymerised commercial cyanoacrylate adhesive on cultured human oral fibroblasts. Aust Dent J 44:248-52.nWeber SC, Chapman MW. 1984. Adhesives in orthopaedic surgery. Clin Orthop 191:249-61.nWerker AM, Kon M. 1997. Review of facilitated approaches to vascular anastomosis surgery. Ann Thorac Surg 63:122-7.nYavuz SS, Kaplan M, Kut MS, Demirtas MM. 2003. Antibacterial effect and antimicrobial contamination risk of ethyl 2-cyanoacrylate, a tissue adhesive used in cardiovascular surgery. Turkish Thorac Cardiovasc Surg 11:141-6.n



How to Cite

Kaplan, M., & Baysal, K. (2005). In Vitro Toxicity Test of Ethyl 2-Cyanoacrylate, a Tissue Adhesive Used in Cardiovascular Surgery, by Fibroblast Cell Culture Method. The Heart Surgery Forum, 8(3), E169-E172.