Structurally coupled polysaccharide-lignin tri-domain phyto-cryogel for microenvironment buffering of oxidative and microbial stress in diabetic wounds.

Infected diabetic wounds face a dual therapeutic challenge of rapid biomaterial degradation under combined oxidative-osmotic stress, and mechanical collapse of conventional redox-active polysaccharide gels upon prolonged wet-state exposure. To address these challenges, we engineered a tri-domain phyto-cryogel integrating oxidized lignin, gum Arabic, and Aloe vera into an interpenetrating architecture. A covalently crosslinked poly (N-vinylpyrrolidone-co-N,N'-methylenebisacrylamide) [poly(NVP-co-MBAM)] backbone provides wet-state persistence. At the same time, hydrogen-bond-rich polysaccharide domains maintain hydration under hyperosmotic challenge, and lignin-derived phenolic motifs contribute radical-scavenging capacity. The tri-domain cryogel retained consistent antioxidant activity across seven 2,2-diphenyl-1-picrylhydrazyl (DPPH) cycles (82.4 ± 0.6% to 81.0 ± 0.2%, p > 0.05), whereas binary preparations showed significant decay. In an infected diabetic animal model, the lignin-gum Arabic-Aloe vera (LGA) 0.2% tri-domain cryogel accelerated early-stage wound closure compared to a medical-grade bandage control (38.6% vs. 19.3% by Day 3, p < 0.01), accompanied by reduced cluster of differentiation 68 (CD68) macrophage infiltration, normalized redox ratios, and enhanced angiogenesis. These findings demonstrate that polymer architecture-driven microenvironment buffering, through integrated mitigation of oxidative stress, osmotic stress, and infection, can accelerate diabetic wound healing without relying on drug delivery.