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Nanoparticles composed of poly(alkyl cyanoacrylate) (PACA) have shown great promise due to their biodegradability and high drug loading capacity. Development of optimal PACA nanocarriers requires detailed analysis of the overall cellular impact exerted by PACA variants. We here perform a comprehensive comparison of cabazitaxel (CBZ)-loaded nanocarriers composed of three different PACA monomers, i.e. poly(n-butyl cyanoacrylate) (PBCA), poly(2-ethylbutyl cyanoacrylate) (PEBCA) and poly(octyl cyanoacrylate) (POCA). The cytotoxicity of drug-loaded and empty PACA nanoparticles were compared to that of free CBZ across a panel of nine cancer cell lines by assessing cellular metabolism, proliferation and protein synthesis. The analyses revealed that the cytotoxicity of all CBZ-loaded PACAs was similar to that of free CBZ for all cell lines tested, whereas the empty PACAs exerted much lower toxicity. To increase our understanding of the toxic effects of these treatments comprehensive MS-based proteomics were performed with HCT116, MDA-MB-231 and PC3 cells incubated with PACA-CBZ variants or free CBZ. Interestingly, PACA-CBZ specifically led to decreased levels of proteins involved in focal adhesion and stress fibers in all cell lines. Since we recently demonstrated that encapsulation of CBZ within PEBCA nanoparticles significantly improved the therapeutic effect of CBZ on a patient derived xenograft model in mice, we investigated the effects of this PACA variant more closely by immunoblotting. Interestingly, we detected several changes in the protein expression and degree of phosphorylation of SRC-pathway proteins that can be relevant for the therapeutic effects of these substances.

There are many chemicals that can cause burns. Although they are generally acidic and basic in nature, there are more than one million known chemical compounds, of which 300 have been declared highly hazardous chemical substances by the National Fire Protection Society. Chemical burns account for approximately 10.7% of all burn injuries and 30% of deaths because of burns. Chemicals can be classified as acid, alkali, organic, and inorganic compounds. Acids act by denaturing and coagulating proteins. Alkaline burns cause deeper burns than acid burns., (© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Nail tips are nail art materials that can be attached to the nail with adhesives. Recently, nail/finger injuries related to nail tips have been reported and one of the causes is considered to be the adhesives used for attaching nail tips. The components of nail adhesives are mostly cyanoacrylate, which is also used as an industrial instant adhesive. During curing, cyanoacrylate adhesives release formaldehyde through hydrolysis. When it is marketed as a nail adhesive, there is no regulation regarding its formaldehyde amount nor obligation to indicate its ingredients in Japan. Additionally, a biological safety test is not required for nail adhesives. Thus, because the safety of nail adhesives is inadequately confirmed, it is necessary to investigate their biological safety. Therefore, we purchased 5 commercially available nail adhesives and 1 medical adhesive and examined their formaldehyde content and cytotoxicity. We examined the cytotoxicity of the adhesives in V79 cells by a colony forming assay. In this test, 5 nail adhesives showed higher toxicity than 1 medical adhesive. Formaldehyde concentrations in the extract of adhesives were as follows: 17.5 to 24.2 μg/mL for nail adhesives and 7.4 μg/mL for medical adhesives. Cyanoacetate did not elicit cytotoxicity at the final concentration up to 1000 μM. However, formaldehyde showed cytotoxicity, with an IC 50 of 79 μM (2.4 μg/mL). Taken together, the cytotoxicity of nail adhesives could be due to the formaldehyde generated by the hydrolysis of cyanoacrylate. It seems important that nail adhesives will be regulated by obligation and enhanced safety in the future.

Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with different methods and on multiple nanoparticle batches. Here we report the toxicity of poly(alkyl cyanoacrylate) nanoparticles in 12 different cell lines after synthesizing and analyzing 19 different nanoparticle batches and report that large variations were obtained when using different cell lines or various toxicity assays. Surprisingly, we found that nanoparticles with intermediate degradation rates were less toxic than particles that were degraded faster or more slowly in a cell-free system. The toxicity did not vary significantly with either the three different combinations of polyethylene glycol surfactants or with particle size (range 100-200 nm). No acute pro- or anti-inflammatory activity on cells in whole blood was observed., Competing Interests: The authors declare no conflict of interest.

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.

Background and Study Aims: Tissue adhesives are commonly used. The aim of this study was to assess the efficacy and hepatotoxicity of intravenous injection of N-butyl cyanoacrylate versus alpha-cyanoacrylate in a rabbit model., Materials and Methods: A total of 20 rabbits were divided into three groups: group I included four rabbits injected with lipiodol in the dorsal vein of a pinna (control group); group II included eight rabbits injected with N-butyl cyanoacrylate/lipiodol; and group III included eight rabbits injected with alpha-cyanoacrylate/lipiodol. All animals were left under normal living conditions for 1week, and then euthanised. Specimens of ear and liver were taken and fixed in 10% formalin saline for histological examination. Secondary fixation was performed using Bouin solution. Specimens of ear were decalcified in ethylenediaminetetraacetic acid (EDTA) at room temperature for 3months. Then, all specimens were processed, embedded in paraffin, sectioned, and stained with haematoxylin and eosin stains for microscopic examination., Results: Microscopic examination of all specimens of the control group revealed normal structure of pinna and liver tissue. Both test groups demonstrated a wide variability of structural changes ranging from oedema and congestion to necrosis and marked cellular inflammatory infiltration. The two groups were compared using a self-designed inflammatory score. This revealed that alpha-cyanoacrylate caused more venous sclerosis with extensive perivenous reaction and hepatotoxicity than both N-butyl cyanoacrylate and control (p<0.05 and p<0.05). N-butyl cyanoacrylate was also found to cause more venous sclerosis and hepatotoxicity than control (p<0.05)., Conclusion: This study suggested that injection of Krazy Glue, either the clinically usable N-butyl cyanoacrylate or the commercially available alpha-cyanoacrylate, caused comparable venous sclerosis. Unfortunately, both induced significant hepatotoxicity. Therefore, neither of them should be used unless all other safe options are absent. Larger studies have to be conducted and effects of these components on other organs should be investigated; however, caution must be exercised in their clinical use., (Copyright © 2016 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

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.)

Purpose: The present work reports a non-conventional therapeutic strategy based on the use of vaginally-applied formulations for the treatment of trichomoniasis due to Trichomonas vaginalis without adding a drug., Methods: The formulations were based on a thermosensitive pluronic® F127 hydrogel containing mucoadhesive poly(isobutylcyanoacrylate) nanoparticles coated with a mixture of chitosan and thiolated chitosan (75/25 wt%). The nanoparticles were obtained by anionic emulsion polymerization of isobutylcyanoacrylate. The anti-T. vaginalis activity of the formulations was evaluated in vitro., Results: Chitosan-coated nanoparticles showed a strong anti-T. vaginalis activity at 100 μg/mL independently on the proportion of thiolated chitosan. No anti-T. vaginalis activity was reported neither with chitosan-uncoated poly(isobutylcyanoacrylate) nanoparticles nor with chitosan used as a solution. These results suggest that the anti-T. vaginalis activity was related to poly(isobutylcyanoacrylate) nanoparticles but only when they are coated with chitosan. Histological analysis of ex vivo pig vaginal mucosa in contact with pluronic® F127 hydrogel containing poly(isobutylcyanoacrylate) nanoparticles coated with the mixture chitosan/thiolated chitosan (75/25 wt%) did not reveal any toxicity., Conclusion: This study demonstrated that poly(isobutylcyanoacrylate) nanoparticles coated with chitosan were active against T. vaginalis without adding a drug. Besides their anti-T. vaginalis activity, the formulations are non-toxic towards pig vaginal mucosa.

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.)

Background: Eyelash extensions are applied on top of customers' lashes using instant glue containing cyano acrylate, known to cause occupational rhinitis (OR) and occupational asthma (OA). The number of beauty professionals applying these extensions is increasing due to their popularity., Aims: To report on a case of OA with OR and a case of OR attributable to lash extension glue and to evaluate respiratory exposure in lash extension work., Methods: Two beauty professionals with suspected OA and/or OR underwent inhalation challenge, including both control challenge and work-mimicking challenges using the lash extension glue, each with a 24-h follow-up. Volatile organic compounds (VOCs) present were assessed during the lash extension glue challenge. The glues were analysed for their (meth)acrylate content., Results: Both beauty professionals (case 1 and case 2) applied lash extensions regularly for several hours per day as part of their work and had work-related rhinitis. Case 1 had a longer history of lash extension work and also had asthmatic symptoms. The first lash extension glue challenge was negative in both cases, but positive OR reactions were detected in the second test. Case 1 also had a late asthmatic reaction. During the lash extension glue challenge, VOC were present in total concentrations below the irritant threshold and ethylcyanoacrylate (ECA) was detected in a concentration of 0.4mg/m(3). Chemical analysis of the glues revealed ECA was the major component., Conclusions: Application of eyelash extensions using small amounts of cyanoacrylate-based glues can cause OA and OR.

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.)

Objective: To evaluate histologic reactions to 8 suture materials and cyanoacrylate tissue adhesive (CTA) in the musculature and skin of ball pythons., Animals: 30 hatchling ball pythons., Procedures: In each snake, ten 1-cm skin incisions were made (day 0). At 8 sites, a suture of 1 of 8 materials was placed in the epaxial musculature, and the incision was closed with the same material. One incision was closed by use of CTA. No suture material was placed in the tenth incision, which was allowed to heal by second intention (negative control). Snakes (n = 5/group) were euthanized for harvest of treatment-site tissues at days 3, 7, 14, 30, 60, and 90. Skin and muscle sections were examined microscopically and assigned a subjective score (0 to 4) for each of the following: overall severity of inflammation, fibrosis, number of macrophages, number of granulocytes, number of perivascular lymphocytes, and degree of suture fragmentation., Results: Subjective score analysis revealed that CTA did not cause a significant inflammatory response, compared with the negative control. All suture materials caused significantly more inflammation over all time points; for all suture materials, inflammatory response scores were significantly higher than values for the negative control 90 days after implantation. No sutures were completely absorbed by the end of the study period, and several sutures appeared to be in the process of extrusion., Conclusions and Clinical Relevance: In snakes, CTA can be used to close small superficial incisions or lacerations with minimal inflammatory response, and sutures may undergo extrusion from tissues prior to complete absorption.

The aim was to synthesize and characterize fucoidan-coated poly(isobutylcyanoacrylate) nanoparticles. The nanoparticles were prepared by anionic emulsion polymerization (AEP) and by redox radical emulsion polymerization (RREP) of isobutylcyanoacrylate using fucoidan as a new coating material. The nanoparticles were characterized, and their cytotoxicity was evaluated in vitro on J774 macrophage and NIH-3T3 fibroblast cell lines. Cellular uptake of labeled nanoparticles was investigated by confocal fluorescence microscopy. Results showed that both methods were suitable to prepare stable formulations of fucoidan-coated PIBCA nanoparticles. Stable dispersions of nanoparticles were obtained by AEP with up to 100% fucoidan as coating material. By the RREP method, stable suspensions of nanoparticles were obtained with only up to 25% fucoidan in a blend of polysaccharide composed of dextran and fucoidan. The zeta potential of fucoidan-coated nanoparticles was decreased depending on the percentage of fucoidan. It reached the value of -44 mV for nanoparticles prepared by AEP with 100% of fucoidan. Nanoparticles made by AEP appeared more than four times more cytotoxic (IC(50) below 2 μg/mL) on macrophages J774 than nanoparticles made by RREP (IC(50) above 9 μg/mL). In contrast, no significant difference in cytotoxicity was highlighted by incubation of the nanoparticles with a fibroblast cell line. On fibroblasts, both types of nanoparticles showed similar cytotoxicity. Confocal fluorescence microscopy observations revealed that all types of nanoparticles were taken up by both cell lines. The distribution of the fluorescence in the cells varied greatly with the type of nanoparticles., (Copyright © 2011 Elsevier B.V. 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.

Polymer nanoparticles are designed as nanovehicles to carry drugs in the body in a controlled manner increasing the concentration of the biologically active substance in the diseased organs and cells. The safety and biocompatibility of these nanosystems are those of the many properties that nanoparticles must meet to be used in vivo. Here we show that the cytotoxicity profile of poly(isobutylcyanoacrylate) (PIBCA) nanoparticles is affected by the way the nanosystems were produced and by the design of their surface. It was found that the tolerance of PIBCA nanoparticles by cells could be improved up to 100-fold by coating their surface with polysaccharides and haemoglobin.

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.

This study describes occupational exposure to acrylates and other solvents during nail sculpturing, including comparative measurements of the exposure using four different sculpturing methods: The acrylic method, the UV-gel method, the acrylic powder method and the resin method. Thirty-two nail technicians working in 22 different salons participated in the study. In total, 92 measurements were performed, comprising 70 solvent measurements and 22 measurements of ethyl 2-cyanoacrylate. The solvents most frequently present in all samples were acetone, ethyl acetate, toluene and n-butyl acetate, measured in 96%, 94%, 91% and 81% of the samples, respectively. The study shows that the overall solvent exposure was low, with all measurements calculated as the additive effect (n = 70) below 20% of the OEL (arithmetic mean 0.06 and range 0.01-0.19). No statistically significant difference between sculpturing methods were observed (p = 0.05).

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.

Antisense oligonucleotides (AS-ONs) are specific drugs to inhibit gene expression at the transcriptional level. They possess a poor bioavailability and can be degraded by nucleases very rapidly. Therefore, a strong need for the development of oligonucleotide drug delivery systems exists. In the present study, two commercially available liposomes (DOTAP, lipofectin), one artificial virus capsoid (polyoma VP1), two cationic acrylate nanoparticles and two protamine-based nanoparticle preparations (proticles) were compared. Physical parameters of all carrier systems including z-average size, size distribution and surface charge regarding were determined. Cellular uptake was measured by a microplate fluorescence quantification method and, in addition, was visualized in mouse fibroblasts by confocal laser scan microscopy (CLSM). A comparison of cytotoxicity of the different drug delivery systems was performed in vitro using a MTT assay. Mouse fibroblasts which were stable transfected with the cDNA of a N-methyl-D-aspartate (NMDA) receptor also served as functional antisense oligonucleotide test system based on excitotoxicity (cell death). In addition, the efficiency of our oligonucleotide delivery systems was compared on the level of protein expression by Western blotting. Concluding the results, an increased uptake of the ON was found (2-18-fold) for all delivery systems compared to the free ON. Protamine-based nanoparticles showed a very low cytotoxicity in contradiction to all other carrier systems. Lipofectin could be identified as the most potent delivery system in terms of antisense effect, followed by protamine nanoparticles and DOTAP. Sequence-specific antisense effects up to 80% were observed in the functional cell death assay. The highest reduction of NMDA expression was obtained from liposomal preparations with approximately 60% analyzed by Western blot.

Purpose: Nanoparticles are able to enhance drug or DNA stability for purposes of optimised deposition to targeted tissues. Surface modifications can mediate drug targeting. The suitability of nanoparticles synthesised out of porcine gelatin, human serum albumin, and polyalkylcyanoacrylate as drug and gene carriers for pulmonary application was investigated in vitro on primary airway epithelium cells and the cell line 16HBE14o-., Methods: The uptake of nanoparticles into these cells was examined by confocal laser scan microscopy (CLSM) and flow cytometry (FACS). Further the cytotoxicity of nanoparticles was evaluated by an LDH-release-test and the inflammatory potential of the nanoparticles was assessed by measuring IL-8 release., Results: CLSM and FACS experiments showed that the nanoparticles were incorporated into bronchial epithelial cells provoking little or no cytotoxicity and no inflammation as measured by IL-8 release., Conclusions: Based on their low cytotoxicity and the missing inflammatory potential in combination with an efficient uptake in human bronchial epithelial cells, protein-based nanoparticles are suitable drug and gene carriers for pulmonary application.

Cyanoacrylate (CA) and its homologues have a variety of medical, dental and commercial applications as adhesives. The increasing use of CA in dentistry, particularly as an adhesive and sealing glue, has raised concerns regarding its potential toxicity in humans. Reported toxicity of CA is uncommon in the dental workplace, but may manifest as conditions such as urticaria, contact dermatitis and other dermatoses. Dental staff using CA adhesives should avoid direct contact with CA and use appropriate personal protective measures. Maintaining higher levels of humidity, optimizing room ventilation and using special air conditioning filters in the working environment may be useful in minimising the toxicity of volatile CA adhesives.

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)

Cyanoacrylate has been used in medicine and dentistry for many years. It has been used as a postextraction dressing and retrograde filling material in endodontic surgery. The aim of this study was to evaluate the cytotoxic effects of Histoacryl and other two homologue ethyl cyanoacrylates, Super Bonder and Ultrabond, on cultured fibroblasts, using the Trypan blue dye exclusion assay. The cyanoacrylates were applied to round glass coverslips, which were placed in contact with NIH 3T3 cells. After 0, 6, 12 and 24 h (short-term assay; viability) and 1, 3, 5 and 7 days (long-term assay; survival), the cells were examined under phase light microscopy and counted. The data were compared by the Kruskal-Wallis test. In the short-term experiments, only the cultures of the Ultrabond group (GIV) presented significant smaller percentages of cell viability than the cultures of the other groups (GI: control; GII: Super Bonder; GIII: Histoacryl). Although the cultures of the Super Bonder group (GII) presented smaller percentages of cell viability than cultures of the other groups (GI, GIII, GIV) at the long-term assay, this group was the only experimental group presenting a continuous and progressive cell growth. Our results have shown an in vitro biocompatibility of Histoacryl and ethyl cyanoacrylate homologues. These cyanoacrylates could therefore be of importance for endodontic purposes.

Background and Purpose: To compare the efficacy and vascular toxicity of embolization with radical (NBCA+metacryloxysulpholane=CS) versus conventional anionic (NBCA alone=CA) polymerization of NBCA., Materials and Methods: Under continuous digital subtracted angiography (DSA) recordings, a 0.2 mL volume of identical glue mixtures were injected in a single-step procedure, concomitantly, in left and right (with CS and CA, respectively) renal arterial branches (RAB) and ascending pharyngeal arteries (APA) in 8 swines. Arterial histopathology and morphometry of inflammation were investigated at 2 weeks., Results: Complete embolization was achieved with equivalent cast homogeneity on DSA with both NBCA mixtures in RAB and APA. Inflammatory crowns in APA and RAB were significantly lower in CS - than in CA-treated sites (p<0.001). CS plug was scarcely adhesive to the vascular wall, and pulled apart from the wall by a residual thrombotic lining; in contrast with CA casts that were strongly adhesive to walls with endothelium stripping., Conclusions: Anionic and radical polymerization of NBCA embolization was identical with regards to occlusion rate; whereas radical pathway of polymerization with cyanoacrylates lowered histotoxicity with a less sustained adhesiveness of casts against vascular walls.

Endovascular neurosurgery is now becoming available as one of strategies for the treatment of cerebro-spinal arterio-venous malformations and aneurysms. For this treatment, a microcatheter is advanced into or close to a lesion and then an embolic material is administered through it to obliterate the lesion. N-butyl-2-cyanoacrylate (NBCA) has preferentially been used as an embolic material in Europe and America. However, its exceptionally strong adhesive force sometimes causes adhesion between the tip of the microcatheter and the artery. In this study, a new non-adhesive cyanoacrylate, isostearyl-2-cyanoacrylate (ISCA), was developed. It carries a long hydrophobic side isostearyl group with lower reactivity and adhesion than other cyanoacrylates. Its polymerization rate is, however, too low to obliterate a vascular lesion with a rapid blood flow. To increase the polymerization rate. ISCA was mixed with NBCA. As a result, the adhesive force of the mixture became extremely low, compared with that of NBCA. The viscosity of the mixture was low enough to allow its' use as an embolic material. Tissue reactions against the mixture was milder than those against NBCA. Radio-angiography became possible by mixing further with Lipiodol. The evaluation of this new embolic material with a rabbit renal artery showed that the obliteration effect of the mixture of ISCA and NBCA was excellent to use as an embolic material for clinical applications.

Cyanoacrylates have known for their ability to polymerize rapidly in the presence of traces of weakly basic moieties such as water. The tissue adhesive, Histoacryl(R) (N-butyl 2-cyanoacrylate), has been reported to control bleeding through endoscopic sclerotherapy. But the commercially available Histoacryl(R) is expensive, and it has the problem like other cyanoacrylates that the glue tends to flow/run away from the point of application, which is inherent to the low viscosity, making precise application difficult. In this study, ethyl cyanoacrylate (ECA), the main constituent of "super glue," was employed instead of Histoacryl(R) due to its lower cost. The aim of the research is to modify the compositions of ECA regimen and evaluate its feasibility for sclerosant application through both in vitro flow circuit model and in vivo animal tests. It was noted that the difference in the relative hardening rate between the in vitro Hepes-Tyrodes buffer flowing model and the in vivo rat model for the ECA and Histoacryl(R) was related to the existence of the blood protein, such as albumin, in the physiological milieu. It was also noticed that the ECA setting rate was greatly increased either in Hepes-Tyrodes buffer or in blood (to a comparable rate as Histoacryl(R) in vivo) by adding a few doses of caffeine, which acts as a polymerization initiator. This would lead to far better injection precision during sclerotherapy. Furthermore, in vivo histological examination for the occluded lumen of the rat's inferior vena cava and a clinical piglet portal vein occlusion experiment have suggested this new sclerosant regimen, caffeine/ECA, is of great promise in endoscopic sclerotherapy., (Copyright 2000 John Wiley & Sons, Inc.)

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.

Purpose: The nature of interactions between macrophages and drug carriers is of primordial importance either in the design of more effective therapeutic strategies for macrophage-associated pathogenesis or in establishing new approaches for pharmacological action avoiding macrophages., Methods: Polyalkylcyanoacrylate nanoparticles (PMCA, PECA, PBCA and PIBCA nanoparticles) were assayed for their toxicity on peritoneal resident and thioglycolate-elicited macrophages. Cellular viability was assessed by MTT tetrazolium salt assay, oxidative burst by NBT reduction and NO production by nitrite evaluation., Results: The nanoparticles tested led to cellular morphological modifications and induced toxicity in both types of macrophages in culture. The polyalkylcyanoacrylate nanoparticles uptake by peritoneal macrophages caused an increase in respiratory burst, as assessed by the NBT reduction assay, and induced the release of soluble toxic factors to the culture medium. The association of LPS with the PMCA nanoparticles significantly stimulated the production of nitric oxide (NO) by resident macrophages. In contrast, the association of PBCA nanoparticles with LPS does not increase the nitrite production as compared with LPS alone, which may be due to a different physico-chemical interaction between LPS and the two types of polymers., Conclusions: In cultured mice peritoneal macrophages, nanoparticles of PACA induce the production of oxygen reactive products, which cause changes in the cell metabolism of both resident and elicited macrophages. PMCA nanoparticles in association with LPS significantly increase the expression of the inducible isoform of nitric oxide synthase, leading to the release of large amount of NO, which may be highly cytotoxic to the cultured cells in the presence of peroxide generated from the oxidative burst.

Intravenous administration of drug-loaded polyalkylcyanoacrylate (PACA) nanoparticles is followed by a rapid uptake by the tissues of the reticuloendothelial system, mainly the liver. Nevertheless, it is so far unknown whether chronic administration of nanoparticles can lead to damage to the liver cells. We have studied the subacute toxicological effects of these drug carriers in a rat in vivo/ex vivo model. Nanoparticles were administered intravenously at a total dose of 200 mg/kg for 14 days (10 individual doses of 20 mg/kg). Hepatocytes were then isolated. Levels of alpha 1-acid glycoprotein secretion increased while albumin secretion decreased in hepatocytes from rats treated with PACA nanoparticles. In addition, glucose production due to the fructose metabolism was lowered. Treated rats induced a temporary increase and hyposialyation of serum alpha 1-acid glycoprotein. These effects were reversible 15 days after the treatment was concluded. Finally, the involvement of Kupffer cells and polymer degradation products was studied in vitro. Modifications of hepatocyte protein synthesis related to the treatments were only observed when direct contact between nanoparticles and hepatocytes existed. Kupffer cells and polymer degradation products did not mediate the hepatocyte response to nanoparticles in vitro. In conclusion, modifications in hepatic function after chronic administration of PACA nanoparticles have been detected by the use of very sensitive models for detecting hepatoxicity. These effects were, however, found to be reversible when the treatment was stopped.

Acute doxorubicin-loaded nanoparticle (DXNP) renal toxicity was explored in both normal rats and rats with experimental glomerulonephritis. In normal rats, 2/6 rats given free doxorubicin (DX) (5 mg/kg) died within one week, whereas all control animals and all rats having received free NP or DXNP survived. A 3 times higher proteinuria appeared in animals treated with DXNP than in those treated with DX. Free NP did not provoke any proteinuria. Two hr post-injection, DXNP was 2.7 times more concentrated in kidneys than free DX (p < 0.025). In rats with immune experimental glomerulonephritis, 5/6 rats given DX died within 7 days, in contrast to animals treated by DXNP, NP, or untreated, which all survived. Proteinuria appeared in all series, but was 2-5 times more intense (p > 0.001) and prolonged after doxorubicin treatment (400-700 mg/day), without significant difference between DXNP and DX. Rats treated by unloaded NP behaved as controls. These results demonstrate that, in these experimental conditions, DXNP killed less animals than free DX, despite of an enhanced renal toxicity of the former. Both effects (better survival and nephrosis) are most probably related to an enhanced capture of DXNP by cells of the mononuclear phagocyte system, including mesangial cells.

The use of a tissue adhesive for surgical procedures has prompted a large number of clinical and experimental studies. Alkyl-2-cyanoacrylate esters constitute a family of adhesives with good mechanical properties but their biological compatibility has to be assessed. In this study the cytotoxicity of three commercially available cyanoacrylates and one of unknown composition has been determined. The first part of the study deals with direct contact testing procedures using L 929 cells challenged with drops of adhesives: cell morphology, cell growth and bacterial growth inhibition were assayed. Testing methods included cell viability assay using vital dyes, cell growth measurement using crystal violet staining uptake and bacterial growth assay using S. aureus growth inhibition. All the cyanoacrylate adhesives tested were found to be cytotoxic and to inhibit cell proliferation: differences between the cyanoacrylates were found.

Comparative cytotoxicity testing of four cyanoacrylate adhesives suggested for orthopaedic applications was performed. These substances were placed in complete culture medium with serum and the resulting extraction fluids were tested on L 929 cells and human lymphocytes. Testing procedures include cell morphology assessment using light microscopy and vital dyes, cell counting using a computer-assisted image analysis system, cell growth measurement using total protein content assay and cell viability assessment using the MTT method. Quantitation of the toxicity of the degradation products released by cyanoacrylates in the extracts was achieved and differences in the cytopathic effect related to the chemical composition of the cyanoacrylates were found. A toxicity rating of the assayed cyanoacrylate adhesives was obtained as follows (in order of increasing toxicity): BCA < xCA < ECAg < ECAl.

The tetrazolium-based colorimetric assay (MTT test) measures only in vitro living cells and the results are directly related to the number of viable cultured cells. It has been adopted in immunological investigations, cancer research and, recently, biocompatibility evaluation. We used the MTT method with minor modifications to fit it to an in vitro study of biomaterial-cell interactions. The MTT assay was confirmed to be feasible, rapid and reproducible. Moreover, it showed a good correlation with other in vitro proliferation assays, such as the 3H-thymidine uptake assay. By using the MTT method and the ASTM procedure for extracting biomaterials, we quantified the in vitro cell compatibility of different metals and polymers.

To evaluate whether or not the corneal micropocket implantation is effective for determining the toxicity of polymeric materials, currently used biodegradable polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), LA-GA copolymers, and three kinds of poly(2-cyano-acrylate)s (PCA) were implanted in a rabbit corneal pouch and the tissue responses were observed macroscopically and microscopically. It was found that PLA induced no vascularization, whereas a residual solvent and ethylene oxide gas remaining in the PLA matrix invoked vascularization. Vascularization clearly took place when PGA was implanted in the cornea, which became opaque, probably because of cellular infiltration. In the case of PCA implantation, severe inflammation as well as vascular invasion occurred in the initial stage. It is likely that these tissue reactions were caused by the leachables from the implanted materials, the extent being dependent on the leaching rate and the toxicity. It was concluded that the corneal micropocket assay is a good means to detect trace amounts of leachables from implanted materials without sacrificing the animals with the implanted materials.

Surgical tissue adhesives could simplify complex surgical procedures by stabilizing tissue surfaces through hemostasis, sealing wounds, and fixating tissue in areas inaccessible to suture placement. The most common surgical tissue adhesives available to the surgeon include the cyanoacrylate derivatives and the fibrin tissue adhesives. Butyl-2 cyanoacrylate (Histoacryl) is a cyanoacrylate derivative that is frequently used in Canada and Europe. This adhesive has excellent binding strength for skin closure; however, subcutaneous implantation can result in inflammation and foreign body giant cell reaction. Fibrin tissue adhesives use a fibrin clot as the binding moiety and vary in adhesive strength depending on the fibrinogen concentration of the preparation. Autologous fibrin tissue adhesives are prepared using one of several different methods, which vary in fibrinogen yield and concentration. The currently available autologous fibrin tissue adhesives demonstrate good hemostatic properties with relatively low binding strengths. This article reviews the status of cyanoacrylate adhesives and the preparation, efficacy, and clinical applications of the fibrin tissue adhesives.

A-cyanoacrylate proves to be an advanced means of osteosynthesis. It is particularly indicated for short bone fragments in the articular and comminuted fractures, where a perfect anatomic reduction is required. It is shown to be non-toxic for bone and surrounding tissues and to be endowed with a remarkable chemical bond. It is easily applied and inexpensive. The results are very interesting and stimulate continuation of the studies. The authors think a-cyanoacrylate (or a derivative) is the future of biological osteosynthesis.