Gelatin-derived bioadhesives for closing skin wounds: an in vivo study

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.