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Purpose: Determine the effect of 2-octylcyanoacrylate on placenta derived mesenchymal stromal cells (PMSCs) seeded onto extracellular matrix (ECM) in order to assess its biocompatibility as a potential adhesive for in-vivo fetal cell delivery., Methods: PMSCs isolated from chorionic villus tissue were seeded onto ECM. A MTS proliferation assay assessed cellular metabolic activity at various time points in PMSC-ECM with direct, indirect, and no glue contact. Conditioned media collected prior to and 24 hours after glue exposure was analyzed for secretion of human brain-derived neurotrophic factor, hepatocyte growth factor, and vascular endothelial growth factor., Results: Direct and indirect contact with 2-octylcyanoacrylate results in progressively decreased cellular metabolic activity over 24 hours compared to no glue controls. Cells with direct contact are less metabolically active than cells with indirect contact. 24 hours of glue exposure resulted in suppression of growth factor secretion that is near complete with direct contact., Discussion: Exposure to 2-octylcyanoacrylate results in decreased metabolic activity and decreased measurable secretion of growth factors by PMSCs seeded onto ECM. Thus, the application of 2-octylcyanoacrylate glue should be limited when working with cell-engineered scaffolds as its inhibitory effects on cell growth and secretory function can limit the therapeutic potential of cell-based interventions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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.

Short-chain cyanoacrylates (SCCA), such as ethyl-2-cyanoacrylate (KrazyGlue, Aron Alpha, Columbus, OH) are commonly used as commercial fast-acting glues. Although once used in clinical medicine as skin adhesives, these products caused tissue toxicity and thus their use in live tissue was discontinued. SCCA were replaced by longer-chain versions (LCCA), such as butyl-cyanoacrylate (Vetbond, 3M, St Paul, Minnesota), which were found to be less toxic than the short-chain formulations. Some researchers prefer to use SCCA due to the belief that they create a stronger bond than do the longer-chain counterparts. In survival surgeries, we compared the bone thickness, bone necrosis, fibrosis, inflammation, and bone regeneration in the calvaria of control (naïve), surgery-only, SCCA-treated, and LCCA-treated mice (n = 20 per group). At 1 and 14 d after surgery, all mice except those treated with SCCA showed statistically similar bone measurements to those of the naive control group. The SCCA group had significantly less bone regeneration than did all other groups. These results suggest that the application of SCCA causes bone damage resulting in the loss of bone regeneration. This finding may assist investigators in choosing a tissue glue for their studies and may support the IACUC in advocating the use of pharmaceutical-grade tissue glues.

As poly L-lactic acid (PLLA) is a polymer with good biocompatibility and biodegradability, we created a new tissue adhesive (TA), pre-polymerized allyl 2-cyanoacrylate (PACA) mixed with PLLA in an effort to improve biocompatibility and mechanical properties in healing dermal wound tissue. We determined optimal mixing ratios of PACA and PLLA based on their bond strengths and chemical structures analyzed by the thermal gravimetric analysis (TGA) and Fourier transform infrared (FT-IR) spectroscopy. In vitro biocompatibility of the PACA/PLLA was evaluated using direct- and indirect-contact methods according to the ISO-10993 cytotoxicity test for medical devices. The PACA/PLLA have similar or even better biocompatibility than those of commercially available cyanoacrylate (CA)-based TAs such as Dermabond® and Histoacryl®. The PACA/PLLA were not different from those exposed to Dermabond® and Histoacryl® in Raman spectra when biochemical changes of protein and DNA/RNA underlying during cell death were compared utilizing Raman spectroscopy. Histological analysis revealed that incised dermal tissues of rats treated with PACA/PLLA showed less inflammatory signs and enhanced collagen formation compared to those treated with Dermabond® or Histoacryl®. Of note, tissues treated with PACA/PLLA were stronger in the tensile strength compared to those treated with the commercially available TAs. Therefore, taking all the results into consideration, the PACA/PLLA we created might be a clinically useful TA for treating dermal wounds., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The water-reactive tissue adhesive 2-octyl cyanoacrylate (OCA) was microencapsulated in polyurethane shells and incorporated into Palacos R bone cement. The tensile and compressive properties of the composite material were investigated in accordance with commercial standards, and fracture toughness of the capsule-embedded bone cement was measured using the tapered double-cantilever beam geometry. Viability and proliferation of MG63 human osteosarcoma cells after culture with extracts from Palacos R bone cement, capsule-embedded Palacos R bone cement, and OCA were also analyzed. Incorporating up to 5 wt % capsules had little effect on the compressive and tensile properties of the composite, but greater than 5 wt % capsules reduced these values below commercial standards. Fracture toughness was increased by 13% through the incorporation of 3 wt % capsules and eventually decreased below the toughness of the capsule-free controls at capsule contents of 15 wt % and higher. The effect on cell proliferation and viability in response to extracts prepared from capsule-embedded and commercial bone cements were not significantly different from each other, whereas extracts from OCA were moderately toxic to cells. Overall, the addition of lower wt % of OCA-containing microcapsules to commercial bone cement was found to moderately increase static mechanical properties without increasing the toxicity of the material., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: Cyanoacrylate has been used as a commercial tissue adhesive. Recently, ethyl 2-cyanoacrylate has been suggested for the fixation of onlay autogenous bone graft. However, ethyl 2-cyanoacrylate must be biocompatible with bone tissue. This study evaluated the cytotoxicity of cyanoacrylate adhesives using a direct contact assay on human oral osteoblast cells., Materials and Methods: Osteoblastic cells derived from human alveolar bone of the mandible were cultured with or without cyanoacrylate. The CA1 group contained methyl 2-cyanoacrylate, the CA2 group contained ethyl 2-cyanoacrylate, and the CA3 group did not contain cyanoacrylate (control). This study investigated cell morphology, which included the inhibition zone, and cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which was measured as optical density. Data from the MTT assay were tested statistically using SigmaStat 3.5., Results: Dead cells found around the CA1- and CA2-treated cells constituted inhibitory zones that varied from 200 to 500 μm. There was no inhibitory zone in the CA3 group. Cell viability evaluated by the MTT assay showed that the CA2 and CA3 optical densities were not significantly different. The CA1 optical densities differed significantly from the CA3 optical densities., Conclusions: Within the limits of this study, the MTT method supported the conclusion that ethyl 2-cyanoacrylate is biocompatible according to a direct contact assay on human osteoblast cell cultures and suggests its usefulness in bone graft fixation., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Cyanoacrylate adhesive has been suggested as an alternative to suturing when repairing severed peripheral nerves. The authors examined the cytotoxic effect of ethyl-cyanoacrylate on the human neuroblastoma cell line SH-SY5Y and compared it with the effects of butyl-cyanoacrylate (Histoacryl), an adhesive approved for skin closure. Ethyl-cyanoacrylate or butyl-cyanoacrylate was applied in confluent SH-SY5Y cultures. Immediately, at 24h and at 7, 14, 21 and 28 days, cultures were photographed and analysed digitally. At corresponding intervals, cell death was quantified using a (51)Cr release assay. In cultures exposed to ethyl-cyanoacrylate or butyl-cyanoacrylate, cell death was observed predominantly in conjunction with the adhesive, causing a halo devoid of cells. Surviving cells showed neurodegenerative properties with loss of neuritis and reduction of body size up to 3 days post exposure. The inhibition halo diminished over time in both groups and at 28 days cells reached the margin of the adhesive in the ethyl-cyanoacrylate group. (51)Cr assay indicated significant cell death in exposed cultures, which rapidly decreased during the first 14 days. No significant differences were found between the adhesives. This study demonstrates that ethyl-cyanoacrylate and butyl-cyanoacrylate have a transient cytotoxic effect, which may explain the promising results when using cyanoacrylate for nerve repair., (Copyright 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Bronchopleural fistulas (BPF) and air leaks (AL) present major complications after pulmonary resection. Various tissue sealants have been proposed for their prevention, e.g., fibrin sealant (FS) and cyanoacrylate glues (CA). Contrary to the safety record of FS, substantial side effects such as foreign body reaction and impaired tissue integration have been reported for CA. This study compares the sealing efficacy and biocompatibility as well as side effects of FS and CA in experimental partial pulmonary resection and lung incision in rabbits., Methods: 26 New Zealand white rabbits (3 kg) were randomized to one of the three groups: partial pulmonary resection (A, acute model; n = 7 FS/ 7CA), lung incision [2 (B; n = 3 FS/ 3 CA)], and 14-day observation period (C; n = 3 FS/ 3 CA). In all groups (A, B, and C), FS was considered as control and CA as treatment. Surgery was carried out in general anaesthesia and mechanical ventilation. For partial lung resection a median thoracotomy was performed and the apex of the left median lobe was resected and the parenchymal surface covered with 0.09 ml of FS and CA. The thoracic cavity was filled with ringer solution after 5 minutes. The inspiratory minute volume (IMV) was increased by 0.02 l after every 4th inspiration. In groups B and C, a left lateral thoracotomy was performed in the 4th intercostal space and the left median lobe was incised with a scalpel. The incision was covered with 0.5 ml of FS or CA. At autopsy (B and C) the operation site was assessed macroscopically. Histology was performed in all animals., Results: In terms of sealing purposes, FS and CA yielded comparable results in all groups. CA elicited a substantial increase of tissue temperature in the acute phase immediately after application (A). After 14 days CA residues were found, whereas FS was completely degraded. Histology showed a pronounced inflammatory response to CA but not to FS. We conclude that although the effect of airtight sealing was equally satisfying, our results emphasize that FS is preferable to CA for the prevention of BPF and AL due to superior biocompatibility and degradability. Longterm effects of CA residues on pulmonary tissue require further experimental testing.

Objectives: The aim of this study was to investigate biocompatibility and adhesive properties of 6 tissue adhesives available, when applied between the pancreas and jejunum in an experimental model., Methods: Portion of jejunum was glued on the pancreas in rats with 3 cyanoacrylate derivatives (Histoacryl, Dermabond, and Glubran 2), 2 human fibrin sealants (Tisseel Duo Quick and Quixil), and 1 albuminglutaraldehyde sealant (BioGlue). Pancreatic tissue specimens and blood samples were harvested 1, 3, 7, and 21 days after gluing for histological determination and amylase activity measurement. Pancreaticojejunal attachment created with adhesives underwent tensile strength measurement at each time point. Samples were also taken from unoperated rats and sham-operated rats., Results: Exposure and sham groups both induced a similar increase in amylase activity on day 1 with normalization by day 3. Sham operation induced mild changes in the pancreas. Each tissue adhesive induced changes in pancreatic histology to the entire gland. Injurious effect was more severe with the 3 cyanoacrylates than with the 3 fibrin/semisynthetic glues. Histoacryl and Quixil induced lower tensile strength than the other adhesives., Conclusions: All of the tissue adhesives studied induced histological changes in the pancreas of which at least part might be considered harmful. The potentially harmful tissue effects of the preparations tested might compromise the use of these substances in pancreatic surgery.

Purpose: To compare the bacteriostatic effects, corneal cytotoxicity, and ability to seal corneal incisions among fibrin glue and 2 commercially available cyanoacrylate derivatives: N-butyl cyanoacrylate and methoxypropyl cyanoacrylate., Methods: The bacteriostatic activities of these tissue glues were verified by measuring the zones of bacterial growth inhibition surrounding the adhesive droplets on agar plates inoculated with Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, or Mycobacterium chelonae. Corneal cytotoxicity was tested by a direct contact method by using cultured bovine corneal epithelial cells, keratocytes, and corneal endothelial cells challenged with droplets of adhesives. Each of the cells was treated with droplets of adhesives. The ability to seal corneal incisions was verified by calculating the maximum intraocular pressure resistant to leakage of rabbit corneal stab wounds sealed with tissue adhesives., Results: Methoxypropyl cyanoacrylate and N-butyl cyanoacrylate showed bacteriostatic effects against S. aureus, S. pneumoniae, and M. chelonae but not P. aeruginosa and E. coli. In contrast, fibrin glue had no such effects against either Gram-positive or -negative bacteria (P < 0.01). Methoxypropyl cyanoacrylate showed the highest levels of corneal cytotoxicity, followed by N-butyl cyanoacrylate. Fibrin glue, however, showed minimal cytotoxicity (P < 0.01). Methoxypropyl cyanoacrylate and N-butyl cyanoacrylate also displayed a greater ability to seal corneal incisions than that of fibrin glue (P < 0.01)., Conclusions: The bacteriostatic effects, corneal cytotoxicity, and ability to seal corneal incisions differed among the 3 compounds tested. These different properties should be considered when choosing tissue adhesives during corneal surgery.

Cyanoacrylate (CA) and its homologues have a variety of medical and commercial applications as biological adhesives and sealants. Homologues of CA are being widely promoted in surgery as a tissue adhesive to replace traditional suturing techniques. Potential benefits of using CA adhesives include better cosmetic results, more rapid wound closure, and perhaps most significantly, the potential for significant reductions in percutaneous injuries from suture needles, which would in turn also reduce the risk of transmission of infectious diseases. Nevertheless, certain concerns have been raised regarding the potential toxicity of CA within patients, as well as among health professionals who are occupationally exposed when using CA compounds. Reported toxicity of CA in the workplace may result in dermatological, allergic and respiratory conditions. To help reduce the occupational burden, therefore, medical staff using CA adhesives should avoid direct contact with the compound and use appropriate personal protective measures at all times. Maintaining higher levels of humidity, optimizing room ventilation and using special air conditioning filters in surgical suites and operating theatres may also be useful in minimizing the exposure to volatile CA adhesives.

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 approximately 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.

Purpose: To evaluate the clinical efficacy and the clinical and histopathologic tolerance of a new acrylic tissue adhesive (ADAL-2) versus 8/0 polyglactin sutures (Vicryl) for its use in conjunctival surgery., Method: Experimental study performed on New Zealand albino rabbits. The animals were divided into two groups. Surgery consisted of a conjunctival peritomy of 8 mm in the superior limbus followed by extensive subconjunctival dissection and creation of a flap by two radial cuts. The conjunctiva was then attached to the limbus again by the proposed acrylic tissue adhesive (ADAL-2) or 8/0 polyglactin suture depending on the group. Clinical efficacy of the closure of the conjunctival wound, either with adhesives or sutures, and the clinical and histopathologic tolerance were also evaluated 1, 7, 28 and 42 days after surgery., Results: Both conjunctival surgical closure methods were found to be equal in efficacy concerning their ability to fix the conjunctiva to the limbus. There were no significant clinical and histopathologic tolerance differences between the new tissue adhesive investigated (ADAL-2) and 8/0 polyglactin sutures (Vicryl). Histopathology showed no presence of the adhesive 28 days postoperatively., Conclusions: ADAL-2 tissue adhesive is an efficient conjunctival closure method, very well tolerated by the ocular surface. Its sealing efficiency and its tolerance are similar to 8/0 polyglactin sutures. This new acrylic adhesive has a potential as an alternative for surgical conjunctival sealing in ophthalmic surgery., (Copyright 2003 S. Karger AG, Basel)

Histological changes in and around the arterial walls of rats were investigated following simultaneous topical application of cotton sheet and cyanoacrylate glue. The bilateral common carotid arteries were exposed using sterile techniques, and the test materials were applied to the right artery. The left artery served as a control. Changes in arterial histology were evaluated at 2 weeks, 1 month, 2 months, and 3 months after surgery. Extensive inflammation consisting primarily of histiocytes and multinuclear giant cells was observed around the materials, but tended to decrease by 3 months. Necrosis in the media and fibrosis in the adventitia initially appeared around 2 weeks, and became advanced by 2-3 months. At 2-3 months, disruption of elastic fibers and marked fibrosis in the media were seen, and endothelial proliferation in the intima appeared. Intimal proliferation was observed at both the experimental and other sites of the vessels. The present results suggest that simultaneous use of the test materials can cause the arterial occlusive lesions observed following aneurysmal surgery.

The in vitro cytotoxicity of four cyanoacrylate adhesives was tested using cultures of cells derived from human tendons. All four were found to be cytotoxic, even at concentrations as low as 1.7%, over the experimental period of up to 18 weeks. This study shows that such adhesives in their present state may not be suitable for re-joining cut tendons as their initial and long-term toxicity may hinder the slow healing process of tendons.

Dural defects and CSF leaks are common neurosurgical problems and the search for a suitable sealant continues. The effects of such sealants on meninges and brain have not been previously studied. To study the effect of two commonly used sealants, burrholes were made in 20 rats, with the creation of dural tears which were covered with human cadaveric dura smeared with synthetic (cyanoacrylate) glue and gelatine (GRG) glue. Plain dura, placed in one of the burrholes served as a control. An intense inflammatory reaction was observed with both glues, which was found to persist till the eleventh week.

Alkyl-2-cyanoacrylates exhibit properties suggestive of their use as surgical adhesives; however, their cytotoxic and proinflammatory properties have prevented their widespread application. The question of whether cyanoacrylate cytotoxicity may be due to eicosanoid production was investigated. Endothelial cells from rats were exposed to increased concentrations of isobutyl-2-cyanoacrylate. The products from this exposure promoted enhanced, concentration-dependent thromboxane biosynthesis as detected by platelet aggregation. When platelets were pretreated with 1-carboxyheptylimidazole (2.0 mM), an inhibitor of thromboxane biosynthesis, up to 80% less aggregation was observed. Such aggregation was inhibited using 1-carboxyheptylimidazole in a dose-dependent manner. Treatment of endothelial cells with isobutyl-2-cyanoacrylate and 1-carboxyheptylimidazole did not significantly alter the amount of platelet aggregation. A soluble metabolite of isobutyl-2-cyanoacrylate appeared to activate platelet aggregation. The cytotoxicity associated with the surgical use of alkyl-2-cyanoacrylates may be mediated by enhanced local thromboxane production.

N-butyl-2-cyanoacrylate tissue adhesive was injected into the preretinal space of rabbit eyes to study potential toxicity to the retina. Application of 3.3-10.0 ul of cyanoacrylate tissue adhesive showed localized but definite retinal toxicity. White halos appeared surrounding the preretinal cyanoacrylate immediately after injection with a gradual evolution of the white areas into pigmentary scars by 1 month. Histological examination confirmed severe focal necrosis of the retina. No identifiable distant toxic effects or electrophysiologic changes were observed during the 6-month follow-up period.

The effect of ethyl 2-cyanoacrylate (Aaron-2-Alpha) obtained from two different manufactures was evaluated in 37 cats divided into two groups. The first group (n = 28) received a 9-year-old preparation. The second group (n = 9) received recently acquired adhesive. Aaron-2-Alpha was applied to the left cruciate cortex and left femoral neurovascular bundle under barbiturate anesthesia. Normal saline was applied on the right side for control. Survival was allowed for 2, 4, 7, and 14 days after application of the adhesive. The 2-day survival was excluded in the second group. Neuropathological examination revealed meningeal necrosis, neuronal and axonal degeneration, vascular wall degeneration, thrombosis, and inflammatory reaction in both groups of cats. The compounds tested are far from satisfying the ideal requirements for their safe use. Chemical degradation may take place in the adhesives stored for prolonged periods of time. Adhesives obtained from two different sources may contain adjuvants of different toxicity. Severe local tissue reaction could produce marked neurological deficits when adhesives are applied in critical areas.

The cytotoxicity of methyl- and isobutyl-2-cyanoacrylate adhesives was determined using a rat polymorphonuclear leukocyte suspension. Cell degranulation increased and migration decreased on addition of the alkyl-2-cyanoacrylates to the suspension in a concentration-dependent manner. When acetylsalicylic acid or indomethacin, inhibitors of prostaglandin H synthase, were present, the cytotoxicity observed on addition of the adhesives to the leukocytes decreased up to eightfold in a dose-dependent manner as detected by trypan blue exclusion. Likewise, glutathione peroxidase and superoxide dismutase lowered such cytotoxicity resulting from the cyanoacrylates up to eight- and sevenfold, respectively. The data suggested that the adhesives may have generated lipid hydroperoxides that activated prostaglandin and thromboxane biosynthesis, and participated in membranal oxidation and lysis. Such a mechanism may contribute to understanding the thrombotic events associated with the necrosis observed on application of these adhesives to tissues in vivo.

A rapidly biodegradable tissue adhesive, 1,2-isopropylidene glyceryl 2-cyanoacrylate, was synthesized and characterized by NMR. Bond strength was determined. Three types of corresponding polymers were prepared and evaluated for in vitro and in vivo toxicity. The polymers were generally found to be in the moderately toxic and toxic groups similar to the lower alkyl 2-cyanoacrylates.

Tissues adhesives have been evaluated on rats, during microvascular surgery: the IBC 2 and the GRF glues. The short and long term evolution is studied. The patency rate of the anastomosis is analyzed and the histological aspect is studied. The GRF glue exhibits a rapid resorption rate, but the long term results show a high toxicity against the muscular layers of the artery. The IBC 2 glue has a slower resorption rate and its long term effect are restricted to a foreign body reaction.

The effect of a new tissue adhesive, carbohexoxymethyl 2-cyanoacrylate monomer (Ethicon CHC), was evaluated in six cats divided into two groups. With the cats under barbiturate anesthesia. Ethicon CHC was applied to the left cruciate cortex and the left femoral neurovascular bundle. Normal saline was applied to the right side for control. The first group (n = 4) and the second group (n = 2) were killed 4 and 7 days, respectively, after application of the adhesive. Neuropathological examination revealed meningeal astrocytosis, vascular wall degeneration, hemorrhage, and inflammatory reaction in both groups. This adhesive does not display the ideal property of inertness, which would permit its safe use. Focal tissue reactions caused by the adhesives in sensitive areas of the cortex can result in significant neurological deficit.