Chronic wounds are
characterized by an increased bacterial presence,
alkaline pH, and excessive wound drainage. Hydrogel biomaterials composed
of the carbohydrate polymer chitosan are advantageous for wound healing
applications because of their innate antimicrobial and hemostatic
properties. Here, genipin-cross-linked–chitosan hydrogels were
synthesized and characterized, and their in vitro and in vivo performances were evaluated as a viable
wound dressing. Characterization studies demonstrate that the developed
chitosan–genipin hydrogels were able to neutralize an environmental
pH, while averaging ∼230% aqueous solution uptake, demonstrating
their use as a perfusive wound dressing. Bacterial activity studies
demonstrate the hydrogels’ ability to hinder Escherichia
coli growth by ∼70%, while remaining biocompatible in vitro to fibroblast and keratinocyte cells. Furthermore,
chitosan–genipin hydrogels promote an enhanced immune response
and cellular proliferation in induced pressure wounds in mice. All
together, these results reflect the potential of the developed hydrogels
to be used as a proactive wound dressing.
In recent years, there has been an increased interest in injectable, in situ crosslinking hydrogels due to their minimally invasive application and ability to conform to their environment. Current in situ crosslinking chitosan hydrogels are either mechanically robust with poor biocompatibility and limited biodegradation due to toxic crosslinking agents or the hydrogels are mechanically weak and undergo biodegradation too rapidly due to insufficient crosslinking. Herein, the authors developed and characterized a thermally-driven, injectable chitosan-genipin hydrogel capable of in situ crosslinking at 37 °C that is mechanically robust, biodegradable, and maintain high biocompatibility. The natural crosslinker genipin is utilized as a thermally-driven, non-toxic crosslinking agent. The chitosan-genipin hydrogel's crosslinking kinetics, injectability, viscoelasticity, swelling and pH response, and biocompatibility against human keratinocyte cells are characterized. The developed chitosan-genipin hydrogels are successfully crosslinked at 37 °C, demonstrating temperature sensitivity. The hydrogels maintained a high percentage of swelling over several weeks before degrading in biologically relevant environments, demonstrating mechanical stability while remaining biodegradable. Long-term cell viability studies demonstrated that chitosan-genipin hydrogels have excellent biocompatibility over 7 days, including during the hydrogel crosslinking phase. Overall, these findings support the development of an injectable, in situ crosslinking chitosan-genipin hydrogel for minimally invasive biomedical applications.
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