Zn²⁺ incorporated composite polysaccharide microspheres for sustained growth factor release and wound healing

The development of new wound dressings has always been an issue of great clinical importance and research promise. In this study, we designed a novel double cross-linked polysaccharide hydrogel microspheres based on alginate (ALG) and hyaluronic acid methacrylate (HAMA) from gas-assisted microfluidics for wound healing. The microspheres from gas-assisted microfluidics showed an uniform size and good microsphere morphology. Moreover, this composite polysaccharide hydrogel microspheres were constructed by harnessing the fact that zinc ions (Zn²⁺) can cross-link with ALG as well as histidine-tagged vascular endothelial growth (His-VEGF) to achieve long-term His-VEGF release, thus promoting angiogenesis and wound healing. Meanwhile, Zn²⁺, as an important trace element, can exert antibacterial and anti-inflammatory effects, reshaping the trauma microenvironment. In addition, photo cross-linked HAMA was introduced into the microspheres to further improve its mechanical properties and drug release ability. In summary, this novel Zn²⁺ composite polysaccharide hydrogel microspheres loaded with His-VEGF based on a dual cross-linked strategy exhibited synergistic antimicrobial and angiogenic effects in promoting wound healing.