Alginate-TEMPO conjugate hydrogel with synergistic antioxidant and angiogenic activities for accelerating wound...

Effective management of cutaneous wounds remains a significant clinical challenge, often exacerbated by excessive reactive oxygen species (ROS) in the wound microenvironment. This study developed a novel hydrogel for accelerated wound healing based on a covalent conjugate (Alg-T) of sodium alginate, a natural polysaccharide macromolecule, and a ROS scavenger 4-amino-TEMPO. Two kinds of conjugates with grafting ratios of approximately 3% (Alg-T1) and 8% (Alg-T2) were successfully synthesized. The Alg-T exhibited potent ROS-scavenging activity in vitro and facilitated the formation of stable hydrogels via ionic crosslinking. Notably, Alg-T retained the beneficial biological functions of alginate, significantly enhancing cell migration and promoting macrophage polarization towards the M2 phenotype, in comparation with the control group (p < 0.05). Furthermore, Alg-T also effectively scavenged intracellular ROS in H₂O₂-stimulated macrophages. In a murine full-thickness wound model, topical application of both Alg-T hydrogels led to approximately 97% wound closure by day 12, significantly greater than that observed in the Alg (≈73%), Tempo-A (≈73%), DXM (≈74%) and control groups (≈81%) (p < 0.05). Histological and immunohistochemical analyses also revealed Alg-T hydrogels enhanced re-epithelialization, collagen deposition, and angiogenesis, coupled with reduced inflammatory cell infiltration, compared to the control group (p < 0.05). Finally, the hydrogel demonstrated excellent biocompatibility in vitro and in vivo. Therefore, these findings demonstrate that the Alg-T hydrogel, which combines the synergistic action of Alg and TEMPO with a straightforward synthesis process, offers a promising clinically translatable strategy for cutaneous wound healing.