Cytotoxicity of Cyanoacrylate-Based Tissue Adhesives and Short-Term Preclinical In Vivo Biocompatibility in Abdominal Hernia Repair.
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.
Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain.|Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
Gemma
http://orcid.org/0000-0002-1623-4384
G
Pascual
Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain.|Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
Sandra
S
Sotomayor
Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.|Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Marta
M
Rodríguez
Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.|Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Bárbara
B
Pérez-Köhler
Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Andreé
A
Kühnhardt
Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.|Biomaterials Group, Institute of Polymer Science and Technology (ICTP-CSIC), Madrid, Spain.
Mar
M
Fernández-Gutiérrez
Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.|Biomaterials Group, Institute of Polymer Science and Technology (ICTP-CSIC), Madrid, Spain.
Julio
J
San Román
Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.|Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Juan Manuel
JM
Bellón
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003487:Cyanoacrylates / Q000633:toxicity*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005557:Formaldehyde / Q000633:toxicity; D046449:Hernia, Abdominal / Q000473:pathology*; D059685:Herniorrhaphy; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011817:Rabbits; D014014:Tissue Adhesives / Q000633:toxicity*
D001672:Biocompatible Materials; D003487:Cyanoacrylates; D014014:Tissue Adhesives; D005557:Formaldehyde