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.

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