Development of a biodegradable tissue adhesive based on functionalized 1,2-ethylene glycol bis(dilactic acid). II.

Abstract

In body regions where damage and bleeding must be avoided, a substitute for mechanical tissue fixation by sutures or staplers is needed. Since tissue adhesives provide easy and fast handling they are a promising alternative. The present study reports the development and analysis of a tissue adhesive that consists of two adhesive components: hexamethylene diisocyanate (HDI) functionalized 1,2-ethylene glycol bis(dilactic acid) (ELA-NCO) and chitosan chloride. This composition was chosen based on preliminary studies on several chain elongation agents. The present study evaluates this adhesive system by IR-spectroscopy, tensile tests, and gel point measurements in comparison to fibrin glue. The system's in vitro biocompatibility was tested with mouse fibroblasts (L929) according to ISO 10993-5. Furthermore, an implantation study was performed in SPF-Wistar rats. The adhesive strength of manually applied mixtures or mixtures applied by double chamber syringes with a mixing extruder was determined to be significantly higher than that of fibrin glue on bovine muscle tissue at 37°C. Tensile strength increased further when exposure time of the adhesive was increased from 10 min to 48 h. The rheological gel point determination showed that the mixture of ELA-NCO/DMSO and chitosan chloride offers a time window large enough to readjust the fused joint during surgery, as opposed to fibrin glue. Additionally, the in vitro and in vivo biocompatibility studies of the adhesive system revealed no toxic effects on the surrounding tissue.