(613c) Cytocompatibility of Dextran-Based Tissue Sealants for Surgical Wound Closure

We have developed the ActaMax™ sealant family of hydrogel tissue adhesives, formed by reacting an oxidized polysaccharide with a water-dispersable multi-arm polyether amine. Specifically, we have developed tissue adhesives composed of two components: dextran aldehyde and multi-arm PEG amine, which undergo a Schiff base reaction to form a crosslinked hydrogel. This two-component tissue adhesive system crosslinks in water, cures rapidly (<1 min) at room temperature, adheres to moist tissue, and degrades hydrolytically.

The effects of dextran-based tissue adhesives on cell survival and inflammatory cell activation were determined using in vitro mouse cell cultures. Cytotoxicity of tissue adhesives was evaluated by placing adhesives in direct contact with 3T3 fibroblast cells. Polysaccharide-based tissue adhesives composed of dextran aldehyde and star PEG amine were non-cytotoxic to fibroblasts; in contrast, a commercial adhesive composed of 2-octyl cyanoacrylate was highly cytotoxic to fibroblasts. The inflammatory potential of tissue adhesives was evaluated by exposing J774 macrophage cells to adhesives, and measuring TNF-alpha release from macrophages. Polysaccharide-based tissue adhesives did not elicit inflammatory TNF-alpha release from macrophages. These results suggest that dextran-based tissue adhesives are non-cytotoxic and non-inflammatory; the results are therefore significant in the design of novel tissue sealants, as well as cell culture systems to study biomaterials.