Multifunctional protein-polysaccharide hydrogel with antimicrobial and angiogenic properties to promote infected wound healing

Bacterial infections, slow angiogenesis, and wound irregularities continue to present great clinical challenges in infected wound repair. While recent years have seen increasing interest in advanced composite hydrogels with antibacterial, angiogenic, and wound-healing properties, traditional dynamic hydrogels remain limited by inadequate mechanical strength despite their adaptability to irregular wounds. Here, we used double-bonded functionalized recombinant collagen (CFGMA), sulfhydrylated hyaluronic acid (HA-SH), silver ions (Ag⁺), and VEGF peptide (V-pep), which formed a composite hydrogel that could accommodate irregular wounds as well as have excellent mechanical properties. The CFGMA/HA-SH/Ag⁺/V-pep hydrogel not only exhibits excellent antibacterial properties, but also has good anti-inflammatory, pro-proliferative and angiogenic effects. In vitro study results indicated that the CFGMA/HA-SH/Ag⁺/V-pep hydrogel promoted the polarization of macrophages from M1 to M2 type, enhanced the proliferation of L929 and HUVECs, and facilitated the angiogenesis of HUVECs. In vivo experiments indicated that CFGMA/HA-SH/Ag⁺/V-pep hydrogel effectively killed bacteria, accelerated blood vessel regeneration, and promoted the repair of infected wounds at day 12. Moreover, CFGMA/HA-SH/Ag⁺/V-pep hydrogel promoted the regeneration of granulation tissue and collagen deposition at the wound site. The prepared hydrogel was antimicrobial, anti-inflammatory, pro-proliferative, promoted vascular regeneration and accelerated wound repair, which could be an effective treatment for infected wounds.