Ellagic Acid-Cyclodextrin Inclusion Complex-Loaded Thiol-Ene Hydrogel with Antioxidant, Antibacterial, and Anti-inflammatory Properties for Wound Healing.

Hydrogel dressings not only have basic functions such as swelling, water retention, gas permeability, and good biocompatibility but also can be endowed with advanced functions such as antibacterial, antioxidant, adhesion, hemostasis, and anti-inflammation, which make hydrogels have great application potential in clinical trauma. However, the complexity of the wound healing process makes the development of multifunctional wound dressings a great challenge. In this work, based on the thiol-ene photoclickable PEG hydrogel, the inclusion complex of the hydrophobic drug ellagic acid (EA) with mono-(6-mercapto-6-deoxy)-β-cyclodextrin (SH-β-CD) participated in the formation of a hydrogel as a crosslinker. The drug EA with antioxidant, antibacterial, and anti-inflammatory activities was introduced into the hydrogel. This strategy increases the loading capacity of the hydrogel for EA and endows the hydrogel with multifunctional properties. Then, dithiothreitol was added to adjust the mechanical stiffness of the hydrogel to meet the requirements of the wound dressing. Our results demonstrated that this wound dressing has excellent cytocompatibility, antioxidant, antibacterial, and anti-inflammatory activities. Furthermore, the results of the infected wound healing model experiment in rats confirmed that the hydrogel has the ability to rapidly shrink the wound area, prevent wound infection, and promote angiogenesis and collagen deposition. All these results suggest that this hydrogel could be a candidate for the treatment of infected wounds and shed new light on the development of multifunctional wound dressings.