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

Bioadhesives have been used in surgery as hemostatic and wound healing agen ts. GRF (gelatin + resorcinol + formaldehyde) glue, composed of a mixture o f gelatin and resorcinol polymerized by the addition of formaldehyde, has b een used for this purpose. Widespread acceptance of the GRF glue, however, has been limited by reports of cytotoxicity due to its release of formaldeh yde upon degradation. It has been suggested by Wertzel et al, that the cyto toxicity problem of GRF glue may be overcome by changing its cross-linking method. The study was, therefore, undertaken to assess the feasibility of u sing a water-soluble carbodiimide or genipin to cross-link gelatin as new b ioadhesives 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 trea ted by either application of test glues or suture increased consistently wi th time during the healing process. Also, the wounds repaired by test glues or suture caused no calcification. The suture used in the study was comple tely resorbed at the wound area in about 6 days postoperatively. However, t he durations required to completely resorb the carbodiimide- or genipin-cro ss-linked glues were approximately the same (9 days), while it took about 1 4 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 indic ated that the biocompatibility of the carbodiimide- or genipin-cross-linked glues was superior to the formaldehyde-cross-linked glue. The results of t his study may serve as a preliminary experimental model for the further inv estigation of both the carbodiimide- and genipin-cross-linked glues when ap plied to human skin closure.