Double Cross-Linked Biomimetic Hyaluronic Acid-Based Hydrogels with Thermo-Stimulated Self-Contraction and Tissue Adhesiveness for Accelerating Post-Wound Closure and Wound Healing

When skin trauma occurs, rapid achievement of the post-wound closure is required to prevent microbial invasion, inhibit scar formation and promote wound healing. To develop a wound dressing for accelerating post-wound-closure and wound healing, a thermo-responsive and tissue-adhesive hydrogel with interpenetrating polymer networks (IPN) is fabricated based on N-dimethylbisacrylamide (NIPAM) and glutaraldehyde (GTA) cross-linked hyaluronic acid (HA). Results not only confirm the thermo-stimulated self-contraction and tissue adhesiveness of the HA-based IPN (PNI-HA), which effectively aids wound closure via mechanical stretch, but also verify the hemocompatibility and cytocompatibility of PNI-HA that tend to accelerate wound healing. In vivo, a mouse model of total skin defect demonstrates that PNI-HA acting as hydrogel sealant significantly achieves the sutureless post-wound-closure at the early stage of wound healing, and then promotes wound healing by reducing inflammatory cells infiltration, promoting angiogenesis as well as reducing collagen deposition. These results indicate that the developed thermo-responsive and tissue-adhesive hydrogel dressing offers a candidate to serve as a tissue sealant for wound healing.