The GG/TA-Zn composite hydrogel enhances diabetic bone defect healing via inflammation regulation and vascular-bone...

Diabetic (DM) bone defect repair poses significant clinical challenges due to chronic inflammation, oxidative stress, and impaired bone metabolism under hyperglycemic conditions. We developed a multifunctional gellan gum/tannic acid‑zinc (GG/TA-Zn) composite hydrogel integrating anti-inflammatory, antioxidant, pro-angiogenic, and osteogenic properties. Leveraging GG's three-dimensional network structure with TA's antioxidant/immunomodulatory capacities and Zn²⁺'s osteogenic activity, the hydrogel exhibited optimized structural stability, swelling behavior, and controlled Zn²⁺ release kinetics. In vitro analyses demonstrated GG/TA-Zn effectively scavenged reactive oxygen species (ROS) while modulating macrophage polarization from pro-inflammatory M1 to regenerative M2 phenotypes, suggesting potential association with NF-κB-related inflammatory signaling pathways based on concomitant reductions in pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and elevations in anti-inflammatory mediators (IL-4, IL-10). The hydrogel enhanced angiogenesis via dual mechanisms - stimulating endothelial cell proliferation/migration while concurrently promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), evidenced by 2.1-fold increased ALP activity, 3.4-fold more mineralized nodules, and upregulated osteogenic markers (Runx2, OCN, OPN). This multifunctional hydrogel provides a promising in vitro platform for diabetic bone repair through microenvironmental modulation and coordinated tissue regeneration, and warrants further in vivo validation to assess its translational applicability in diabetes-associated osseous defects.