Biocompatibility of a Novel Cyanoacrylate Based Tissue Adhesive: Cytotoxicity and Biochemical Property Evaluation (original) (raw)
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Elasticity and safety of alkoxyethyl cyanoacrylate tissue adhesives
Acta Biomaterialia, 2011
Cyanoacrylate glues are easily applied to wounds with good cosmetic results. However, they tend to be brittle and can induce local tissue toxicity. A series of cyanoacrylate monomers with a flexible ether linkage and varying side-chain lengths was synthesized and characterized for potential use as tissue adhesives. The effect of side-chain length on synthesis yield, physical and mechanical properties, formaldehyde generation, cytotoxicity in vitro and biocompatibility in vivo were examined. The incorporation of etheric oxygen allowed the production of flexible monomers with good adhesive strength. Monomers with longer side-chains were found to have less toxicity both in vitro and in vivo. Polymerized hexoxyethyl cyanoacrylate was more elastic than its commercially available and widely used alkyl analog 2-octyl cyanoacrylate, without compromising biocompatibility.
Tissue adhesives: From research to clinical translation
Nano Today, 2021
Sutures, staples, clips and skin closure strips are used as the gold standard to close wounds after an injury. In spite of being the present standard of care, the utilization of these conventional methods is precarious amid complicated and sensitive surgeries such as vascular anastomosis, ocular surgeries, nerve repair, or due to the high-risk components included. Tissue adhesives function as an interface to connect the surfaces of wound edges and prevent them from separation. They are fluid or semi-fluid mixtures that can be easily used to seal any wound of any morphology – uniform or irregular. As such, they provide alternatives to new and novel platforms for wound closure methods. In this review, we offer a background on the improvement of distinctive tissue adhesives focusing on the chemistry of some of these products that have been a commercial success from the clinical application perspective. This review is aimed to provide a guide toward innovation of tissue bioadhesive materials and their associated biomedical applications.
The chemistry of tissue adhesive materials
Progress in Polymer Science, 2014
Each year millions of people sustain traumatic or surgical wounds, which require proper closure. Conventional closure techniques, including suturing and stapling, have many disadvantages. They inflict additional damage on the tissue, elicit inflammatory responses and have a relatively long application time. Especially for the more demanding wounds, where fluids or gasses are to be sealed off, these techniques are often insufficient. Therefore, a large variety of tissue adhesives, sealants and hemostatic agents have been developed. This review provides an overview of such tissue adhesive materials from a polymer chemistry perspective. The materials are divided into synthetic polymer, polysaccharide and protein based adhesives. Their specific properties and behavior are discussed and related to their clinical application. Though each type has its specific advantages, yet few have become standard in clinical practice. Biomimetic based adhesives and other novel products have shown promising results but also face specific problems. For now, the search for better adhering, stronger, easier applicable and cheaper adhesives continues and this review is intended as starting point and inspiration for these future research efforts to develop the next generation tissue adhesives.
PLOS ONE
Postoperative adhesion is a natural phenomenon that occurs in damaged tissue cells. Several anti-adhesion agents are currently used, but there is no leading-edge product with excellent adhesion-preventive effects. The purpose of this study was to develop ideal antiadhesive agents using human-derived acellular dermal matrix (ADM). We developed 5 new biocompatible thermosensitive anti-adhesion barriers (AABs) using micronized humanderived ADM, hyaluronic acid, and temperature-sensitive and biocompatible synthesized polymers. The biocompatibility, anti-adhesion effect, and biodegradability of these AABs were compared with those of commercial thermosensitive anti-adhesion agents. No cytotoxic effects were observed in vitro and in vivo. Animal testing of adhesion resistance confirmed that the adhesion area, strength, and grade of AAB03 were statistically superior to those of the control group. Factors related to adhesion formation, such as lymphocytes, macrophages, microvessels, and collagen fiber density, were observed using specific staining methods; the results confirmed that AAB03 group exhibited significantly lower macrophage counts, microvessel density, and collagen fiber density than the control groups. Furthermore, AAB03 was completely absorbed by 6 weeks. Thus, AAB03 has the potential to be used as a high-performance anti-adhesion agent.
Evaluation of the potential anti-adhesion effect of the PVA/Gelatin membrane
Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2014
A common and prevailing complication for patients with abdominal surgery is the peritoneal adhesion that follows during the post-operative recovery period. Biodegradable polymers have been suggested as a barrier to prevent the peritoneal adhesion. In this work, as a preventive method, PVA/Gelatin hydrogel-based membrane was investigated with various combinations of PVA and gelatin (50/50, 30/70/, and 10/90). Membranes were made by casting method using hot PVA-gelatin solution and the gelatin was crosslinked by exposing UV irradiation for 5 days to render stability of the produced sheathed form in the physiological environment. Physical crosslinking was chosen to avoid the problems of potential cytotoxic effect of chemical crosslinking. Their materials characterization and mechanical properties were evaluated by SEM surface characterization, hydrophilicity, biodegradation rate, and so forth. Cytocompatibility was observed by in vitro experiments with cell proliferation using confocal laser scanning microscopy and the MTT assay by L-929 mouse fibroblast cells. The fabricated PVA/Gel membranes were implanted between artificially defected cecum and peritoneal wall in rats and were sacrificed after 1 and 2 weeks post-operative to compare their tissue adhesion extents with that of control group where the defected surface was not separated by PVA/Gel membrane. The PVA/Gel membrane (10/90) significantly reduced the adhesion extent and showed to be a potential candidate for the anti-adhesion application. V C 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 840-849, 2014.
Histotoxicity of Cyanoacrylate Tissue Adhesive in the Rat
Annals of Surgery, 1965
THE POTENTIAL usefulness to surgeons of an innocuous tissue adhesive has provided the impetus for extended experimental trials of methyl-2-cyanoacrylate. The unique properties of this monomer as an effective adhesive for living wet tissue surfaces,1, 10 are of considerable interest and clinical potential, even though it is becoming increasingly apparent that this substance is histotoxic.7 We have confirmed the necrotizing properties of methyl-2-cyanoacrylate.3' 12 The structural formula of the cyanoacrylate adhesives and their proposed mechanism of polymerization 4 are shown in Fig. 1. The present study is part of an attempt to develop a less necrotizing cyanoacrylate possessing significant adhesive properties. The hypothesis that lengthening the alkoxyl group of the 2-cyanoacrylic acid ester would reduce its histotoxicity has been tested. The adhesive bond strengths, the heats evolved during in vivo polymerization and local responses to methyl-, hexyland decyl-2-cyanoacrylate are reported. Methods Cyanoacrylate Synthesis Methyl-2-cyanoacrylate (Methyl), hexyl-2-cyanoacrylate (Hexyl), and decyl-2-cyanoacrylate (Decyl) were synthesized according to the method of McKeever.9 The alkyl cyanoacetate was allowed to react with paraformaldehyde to form the cyanoacrylate polymer. The cyanoacrylate polymer was then cracked by heating and the monomer fractionally distilled. To the final product were added trace amounts of SO2 and hydroquinone to increase storage stability. Small batches of each monomer stored at-10°C. were warmed to room temperature immediately before use. Monomers were 95 to 98 per cent pure; mass spectroscopy suggested the principal impurity to be acetic anhydride. Implantation Preparations Individually caged Walter Reed strain male white rats weighing 200 to 250 Gm. were given standard laboratory diet and water ad lib. Operative procedures were performed under ether anesthesia observing aseptic technics. The animals were sacrificed by CO2 asphyxiation. Principles of laboratory animal care as promulgated by the National Society for Medical Research were observed. A. Implantation of Monomers. Subcutaneous, hepatic and femoral marrow cavity sites were employed. Through a midline abdominal incision the tips of the right and left anterior liver lobes were resected. The approximately 1 cm.2 cut surface of the right lobe was coated with monomer, using 113
Biocompatible nanostructured solid adhesives for biological soft tissues
Acta biomaterialia, 2017
Over the past few years, the development of novel adhesives for biological soft tissue adhesion has gained significant interest. Such adhesives should be non-toxic and biocompatible. In this study, we synthesized a novel solid adhesive using nanostructured hydroxyapatite (HAp) and evaluated its physical adhesion properties through in vitro testing with synthetic hydrogels and mouse soft tissues. The results revealed that HAp-nanoparticle dispersions and HAp-nanoparticle-assembled nanoporous plates showed efficient adhesion to hydrogels. Interestingly, the HAp plates showed different adhesive properties depending upon the shape of their nanoparticles. The HAp plate made up of 17nm-sized nanoparticles showed an adhesive strength 2.2times higher than that of the conventional fibrin glue for mouse skin tissues. The present study indicates a new application of inorganic biomaterials (bioceramics) as a soft tissue adhesive. Organic adhesives such as fibrin glues or cyanoacrylate derivativ...
Materials
The development of a new skin adhesive that can be used inside and outside the body, which prevents infection and has fewer scars and less side effects, is currently attracting attention from the scientific community. To improve biocompatibility, prepolymer allyl 2-cyanoacrylate (PAC) and 2-octyl cyanoacrylate (OC) were mixed in various proportions and tested for their therapeutic potential as skin adhesives. A series of skin adhesive samples prepared by mixing PAC, OC, and additives with % (w/w) ratios of 100:0:0, 0💯0, 70:0:30, 40:30:30, and 30:40:30 were tested to determine their antimicrobial activity, cell cytotoxicity, and formaldehyde release. The additives include myristic acid and dibutyl sebacate as plasticizers and butylated hydroxyanisole as an antioxidant. It was observed that the samples containing 70% PAC (PAC7) or 40% PAC (PAC4) with 30% additives had the highest antimicrobial activities against various microbial cells and no cytotoxicity regarding in vitro fibrob...