Synthesis, physiochemical characterization, and biocompatibility of a chitosan/dextran-based hydrogel for postsurgical adhesion prevention

Abstract

An amine-functionalized succinyl chitosan and an oxidized dextran were synthesized and mixed in aqueous solution to form an in situ chitosan/dextran injectable, surgical hydrogel for adhesion prevention. Rheological characterization showed that the rate of gelation and moduli were tunable based on amine and aldehyde levels, as well as polymer concentrations. The CD hydrogels have been shown to be effective post-operative aids in prevention of adhesions in ear, nose, and throat surgeries and abdominal surgeries in vivo. In vitro biocompatibility testing was performed on CD hydrogels containing one of two oxidized dextrans, an 80 % oxidized (CD-100) or 25 % (CD-25) oxidized dextran. However, the CD-100 hydrogel showed moderate cytotoxicity in vitro to Vero cells. SC component of the CD hydrogel, however, showed no cytotoxic effect. In order to increase the biocompatibility of the hydrogel, a lower aldehyde level hydrogel was developed. CD-25 was found to be non-cytotoxic to L929 fibroblasts. The in vivo pro-inflammatory response of the CD-25 hydrogel, after intraperitoneal injection in BALB/c mice, was also determined by measuring serum TNF-α levels and by histological analysis of tissues. TNF-α levels were similar in mice injected with CD-25 hydrogel as compared to the negative saline injected control; and were significantly different (P < 0.05) as compared to the positive, lipopolysaccharide, injected control. Histological examination revealed no inflammation seen in CD hydrogel injected mice. The results of these in vitro and in vivo studies demonstrate the biocompatibility of the CD hydrogel as a post-operative aid for adhesion prevention.

A Topical Hydrogel with Deferiprone and Gallium-Protoporphyrin Targets Bacterial Iron Metabolism and Has Antibiofilm Activity

“…Current phase I/II trials of a chitosan-dextran hydrogel demonstrate improved clinical outcomes after sinus surgery (11). When prepared in situ, succinyl-chitosan and dextran-aldehyde form a nontoxic, biocompatible, biodegradable gel that facilitates postoperative wound healing by promoting homeostasis and preventing adhesions (11)(12)(13)(14)(15). The latter is a particularly important postsurgical complication of endoscopic sinus surgery that frequently causes surgical failure (16).…”

Safety and Efficacy of Chitosan-Dextran Hydrogel in the Middle Ear in an Animal Model

“…Chitosan and dextran, which are both naturally derived polysaccharides, are in vivo biodegradable and biocompatible [Khor, 2002;Shkurupiy et al, 2008;Cabral et al, 2014]. The results obtained in this study showed no difference in the ABR thresholds before and 4 weeks after intratympanic injection of CDH, which indicates that CDH has no ototoxic effect on GPs.…”

Characterization of the in vivo host response to a bi‐labeled chitosan‐dextran based hydrogel for postsurgical adhesion prevention

“…CD-25 hydrogel gelation time and the aldehyde level in DA-25 were as previously described. 20,25 SC was sterilized by autoclaving prior to s.c. injection, and DA-25 was sterilized by filtration with 0.22 mm pore-size cellulose acetate filters (Millipore, North Ryde, New South Wales). Unlabeled CD-25 hydrogel was used for the inflammatory response study.…”

“…19 Our group has previously published an optimized route for the synthesis of the chitosan/dextran (CD) hydrogel components, succinyl chitosan (SC), and oxidized dextran (DA). 20 The amine-functionalized SC and DA are mixed in aqueous solutions to form an in situ injectable hydrogel. This CD hydrogel was developed as a post-operative aid in endoscopic sinus surgeries (ESS) in vivo in both animal and human trials.…”

“…25 In vitro cytotoxicity of the CD hydrogel have been reported previously, and found to be nontoxic and biocompatible with L929 fibroblasts. 20 Based on these promising results, a larger scale in vivo biodegradation, biodistribution, and inflammatory response was pursued in this work.…”