Multifunctional Hydrogels Prepared by Dual Ion Cross-Linking for Chronic Wound Healing

The creation of a moist environment and promotion of blood vessel formation are critical for wound healing. Sodium alginate (SA) hydrogel, which has good biocompatibility and is able to provide a moist environment, has been widely used as a wound dressing. However, it lacks antibacterial ability and bioactivities, which would facilitate chronic wound healing. On the basis of the gelation characteristics of SA and the bioactive hardystonite (HS) bioceramic, we designed a unique, bioactive, injectable composite hydrogel through double ion cross-linking, in which divalent ions, such as Ca²⁺ and Zn²⁺ function as cross-linkers; Zn²⁺ also functions as an antibacterial component and as nutrition for wound healing, and Si ions play a key role in determining the bioactivity of the hydrogel. With the controlled release of divalent ions, such as Ca²⁺ and Zn²⁺ from HS, the gelation process of the composite hydrogel could be efficiently controlled. In addition, in vitro results reveal that the composite hydrogel stimulated proliferation and migration of both human dermal fibroblasts and human umbilical vein endothelial cells, and the in vivo results show that the wound-healing process is obviously enhanced, and the formation of epithelium and blood vessels are evidently advanced. This study indicates the potential of the SA/HS hydrogel as a multifunctional injectable wound dressing with the ability to inhibit bacterial growth and stimulate angiogenesis and wound healing.