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.

Development of a novel injectable drug delivery system for subconjunctival glaucoma treatment

“…When used as an LDD system for long-term release, the swelling properties of the hydrogel have to be greatly reduced, which can be achieved by crosslinking HA with ELA-NCO. ELA-NCO is a hydrophobic isocyanate functionalized 1,2-ethylene glycol bis(dilactic), which has been previously investigated as part of a drug eluting tissue adhesive formula [19,22,40]. Micro-CT measurements showed that HA/ELA-NCO has a highly porous structure, which is advantageous for drug release and leads to softness.…”

“…Previously, the biocompatibility of LDD components has been separately demonstrated for both, HA and ELA-NCO [19,41]. Among glaucoma drugs, LA was chosen for drug release experiments, because, as already mentioned, the current literature lacks any data concerning long-term subconjunctival LA delivery.…”

“…HA is a naturally occurring polysaccharide with distinct physicochemical characteristics which is commonly used in ophthalmic microsurgery due to its viscoelastic and hydrophilic properties [18]. ELA-NCO has been previously introduced by our group as a biodegradable tissue adhesive with high adhesive strength and good in vivo biocompatibility [19,20].…”

Development of a fast curing tissue adhesive for meniscus tear repair

“…In one of the employed strategies a two-component adhesive formulation consisting of a hyper-branched adhesive component and a cross-linking mixture with an amine group-containing compound was used. It is known that amine groups have up to 50 times higher reactivity towards isocyanate-groups than hydroxyl groups, and using such composition will allow the glue to cure within significantly shorter times [8, 9, 15]. The adhesive was applied using a double-chamber syringe equipped with a static mixer.…”

“…Few strategies have been employed to speed up the curing rates of isocyanate-terminated polymers. Sternberg et al engaged the use of polymers such as hyaluronic acid, gelatin, chitosan acetate, and chitosan chloride, which were mixed with the isocyanate-terminated adhesive component prior to its application [8, 9]. Another strategy was chosen by Beckman et al .…”