Tissue adhesives are a valuable alternative for mechanical tissue fixation by sutures or staples. Adhesives are desirable in body regions where damage and bleeding must be avoided. Tissue adhesives provide easy and fast handling. This study reports the development of a tissue adhesive based on 1,2-ethylene glycol bis(dilactic acid) (ELA) functionalized with hexamethylene diisocyanate (HDI) to produce isocyanate terminated ELA-NCO which was characterized by NMR and FTIR spectroscopy. ELA-NCO together with chain elongation agents forms an adhesive system suitable for tissue fixation. Several biodegradable polymers, such as hyaluronic acid, gelatin, chitosan acetate, and chitosan chloride were tested as chain elongation agents to obtain an adhesive system and studied on bovine muscle tissue to evaluate their adhesive strength and compared to fibrin glue. Tensile strength of glued joints was determined by a Zwick universal testing machine at ambient temperature. Mixtures of ELA-NCO and chitosan acetate or chloride, showed significantly higher adhesive strength than fibrin glue. Reaction between ELA-NCO and chitosan chloride produced polyurethane was traced by FTIR spectroscopy. NMR, FTIR, and rheological measurements demonstrated that ELA-NCO and chitosan chloride can be sterilized by gamma-rays or superheated water vapor without alterations, respectively. A mixture of ELA-NCO and chitosan chloride can be useful as medical tissue adhesive.

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.

Biodegradability and adhesive-associated local drug release are important aspects of research in tissue adhesive development. Therefore, this study focuses on investigating the in vitro degradation and drug release of a tissue adhesive consisting of hexamethylene diisocyanate functionalized 1,2-ethylene glycol bis(dilactic acid) and chitosan chloride. To prevent infections, ciprofloxacin hydrochloride (CPX·HCl) was incorporated into the adhesive. The influence of CPX·HCl on the adhesive reaction and adhesive strength was analyzed by FTIR-ATR-spectroscopy and tensile tests. The CPX·HCl release was investigated by HPLC. The degradation-induced changes at 37 °C were evaluated by gravimetric/morphological analyzes and micro-computer tomography. The antibiotic potential of the CPX·HCl loaded adhesive was determined by agar diffusion tests. The degradation tests revealed a mass loss of about 78 % after 52 weeks. The adhesive reaction velocity and tensile strength were not influenced by CPX·HCl. Using a 2 mg/g CPX·HCl loaded adhesive an inhibition of all tested bacteria was observed.