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

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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.

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Acknowledgments

We thank the New Economy Research Fund (Grant No.UOO-X0808) for support of this work. We acknowledge Clare Fitzpatrick for the animal studies.

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Authors and Affiliations

  1. Department of Chemistry, University of Otago, Dunedin, 9054, New Zealand

    Jaydee D. Cabral, Marina Roxburgh, Zheng Shi, Liqi Liu, Lyall R. Hanton, Jim Simpson, Stephen C. Moratti & Brian H. Robinson

  2. Department of Microbiology & Immunology, University of Otago, Dunedin, 9054, New Zealand

    Michelle McConnell

  3. Department of Pathology, University of Otago, Dunedin, 9054, New Zealand

    Gail Williams

  4. School of Chemical and Physical Sciences, Victoria University, Wellington, 6140, New Zealand

    Natasha Evans

  5. Department of Surgery-Otorhinolaryngology, Adelaide University, Woodville, Adelaide, SA, 5000, Australia

    Peter J. Wormald

  6. Wakefield Hospital, Wakefield Nasal and Sinus Institute, Wellington, 6021, New Zealand

    Simon Robinson

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  1. Jaydee D. Cabral
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  2. Marina Roxburgh
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  3. Zheng Shi
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  4. Liqi Liu
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Correspondence to Jaydee D. Cabral.

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Cabral, J.D., Roxburgh, M., Shi, Z. et al. Synthesis, physiochemical characterization, and biocompatibility of a chitosan/dextran-based hydrogel for postsurgical adhesion prevention. J Mater Sci: Mater Med 25, 2743–2756 (2014). https://doi.org/10.1007/s10856-014-5292-3

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  • DOI: https://doi.org/10.1007/s10856-014-5292-3

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