Bioadhesives are used for tissue adhesion and hemostasis in surgery. A gelatin-resorcinol mixture crosslinked with formaldehyde (GRF glue) and/or glutaraldehyde (GRG) is used for this purpose. Although the bonding strength of the GRF glue to tissue is satisfactory, concerns about the cytotoxicity of formaldehyde are reported in the literature. It was suggested that the cytotoxicity problem of the GRF glue may be overcome by changing its crosslinking method. The study was therefore undertaken to assess the feasibility of using an epoxy compound (GRE glue), a water-soluble carbodiimide (GAC glue), or genipin (GG glue) to crosslink with a gelatin hydrogel as new bioadhesives. GRF glue and GRG glue were used as controls. The results of our cytotoxicity study suggested that the cellular compatibility of the GAC and GG glues was superior to the GRF, GRG, and GRE glues. The gelation time for the GG glue was relatively longer than the GRF and GRG glues, while no gelation time could be determined for the GAC glue. Additionally, it took approximately 17 h for the GRE glue to become adhesive. The GRF and GRG glues had the greatest bonding strengths to tissue among all test adhesives, while the bonding strengths of the GAC and GG glues were comparable. In contrast, there was almost no bonding strength to tissue for the GRE glue. However, the GRF and GRG glues were less flexible than the GAC and GG glues. Subsequent to the bonding strength measurement, each test adhesive was found to adhere firmly to the tissue surface and underwent cohesive failure during the bond breaking. In conclusion, the GRF and GRG glues may be used as tissue adhesives when their ability to bind tissue rapidly and tightly is required; the GAC and GG glues are preferable when the adhesive action must be accompanied with minimal cytotoxicity and stiffness; and the GRE glue is not suitable for bioadhesion in clinical applications
Bioadhesives are used for tissue adhesion and hemostasis in surgery. A gelatin-resorcinol mixture crosslinked with formaldehyde (GRF glue) and/or glutaraldehyde (GRG) is used for this purpose. Although the bonding strength of the GRF glue to tissue is satisfactory, concerns about the cytotoxicity of formaldehyde are reported in the literature. It was suggested that the cytotoxicity problem of the GRF glue may be overcome by changing its crosslinking method. The study was therefore undertaken to assess the feasibility of using an epoxy compound (GRE glue), a water-soluble carbodiimide (GAC glue), or genipin (GG glue) to crosslink with a gelatin hydrogel as new bioadhesives. GRF glue and GRG glue were used as controls. The results of our cytotoxicity study suggested that the cellular compatibility of the GAC and GG glues was superior to the GRF, GRG, and GRE glues. The gelation time for the GG glue was relatively longer than the GRF and GRG glues, while no gelation time could be determined for the GAC glue. Additionally, it took approximately 17 h for the GRE glue to become adhesive. The GRF and GRG glues had the greatest bonding strengths to tissue among all test adhesives, while the bonding strengths of the GAC and GG glues were comparable. In contrast, there was almost no bonding strength to tissue for the GRE glue. However, the GRF and GRG glues were less flexible than the GAC and GG glues. Subsequent to the bonding strength measurement, each test adhesive was found to adhere firmly to the tissue surface and underwent cohesive failure during the bond breaking. In conclusion, the GRF and GRG glues may be used as tissue adhesives when their ability to bind tissue rapidly and tightly is required; the GAC and GG glues are preferable when the adhesive action must be accompanied with minimal cytotoxicity and stiffness; and the GRE glue is not suitable for bioadhesion in clinical applications.
Bioadhesives have been used in surgery as hemostatic and wound healing agents. GRF (gelatin + resorcinol + formaldehyde) glue, composed of a mixture of gelatin and resorcinol polymerized by the addition of formaldehyde, has been used for this purpose. Widespread acceptance of the GRF glue, however, has been limited by reports of cytotoxicity due to its release of formaldehyde upon degradation. It has been suggested by Wertzel et al. that the cytotoxicity problem of GRF glue may be overcome by changing its cross-linking method. The study was, therefore, undertaken to assess the feasibility of using a water-soluble carbodiimide or genipin to cross-link gelatin as new bioadhesives to close skin wound lesions in a rat model. Formaldehyde-cross-linked counterpart (GRF glue) and a resorbable suture were used as controls. It was noted that the tensile strength of the skin across each wound treated by either application of test glues or suture increased consistently with time during the healing process. Also, the wounds repaired by test glues or suture caused no calcification. The suture used in the study was completely resorbed at the wound area in about 6 days postoperatively. However, the durations required to completely resorb the carbodiimide- or genipin-cross-linked glues were approximately the same (9 days), while it took about 14 days to completely resorb the formaldehyde-cross-linked glue. The healing process for the suture wound repaired was more rapid than those treated by test glues. Of the test glues, the wounds treated by the carbodiimide- or genipin-cross-linked glues induced less inflammatory response and recovered sooner than that treated by the formaldehyde-cross-linked glue. This indicated that the biocompatibility of the carbodiimide- or genipin-cross-linked glues was superior to the formaldehyde-cross-linked glue. The results of this study may serve as a preliminary experimental model for the further investigation of both the carbodiimide- and genipin-cross-linked glues when applied to human skin closure.
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