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

Abstract

BackgroundCyanoacrylate(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.MethodsFormaldehyde 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.ResultsFormaldehyde 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.ConclusionsAlthough 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.

Use of cyanoacrylate adhesive in the surgical management of feline corneal sequestrum: 16 cases (2011‐2018)

“…The cyanoacrylate product used in this study has a relatively low molecular weight, which has been associated with more significant cytotoxicity and inflammatory response in previous studies . However, more recent studies have suggested that this correlation may not be relevant in regard to biocompatibility and healing . The cats in this report, moreover, healed rapidly with no significant complications, suggesting that this product is safe and well tolerated when used as described here.…”

Cyanoacrylic tissue glues: Biochemical properties and their usage in urology

“…Glubran ® , and Glubran-2 ® exert similar effects on blood parametres. [15,19] Montanaro et al [15] reported that when used at high concentrations, adhesives may have cytotoxic effects, however when they are diluted they may lead to adverse effects at an acceptable level. On the other hand they confirmed that when used intensively, adhesives have acceptable levels of tissue compatibility.…”

“…On the other hand they confirmed that when used intensively, adhesives have acceptable levels of tissue compatibility. [15,19] …”

Surface modification of polypropylene surgical meshes for improving adhesion with poloxamine hydrogel adhesive

“…Moreover, the high viscosity of semi‐synthetic adhesives prevents application over a large contact area during laparoscopic surgery . Synthetic cyanoacrylates adhesives have the advantages of fast fixation and adequate adhesive strength for hernia repair, but in vitro cytotoxicity due to formaldehyde release and in vivo tissue toxicity have been reported …”