Engineered bioadhesive hydrogel loaded with exosomes facilitates diabetic wound healing via M2 macrophage polarization and angiogenesis

• One-step synthesized dual-network PDA-HA overcomes the non-adhesive nature of HA. • PDA-HA intrinsically mitigates high glucose-induced endothelial dysfunction. • PDA-HA@Exo ensures sustained localized exosome release via tissue adhesiveness. • PDA-HA and exosomes synergistically accelerate diabetic wound healing. • PDA-HA@Exo facilitates angiogenesis and M1-to-M2 reparative macrophage polarization. Chronic diabetic wounds persist as a formidable clinical challenge globally due to their intricate pathological environment. Although exosome-based therapies have shown promise for diabetic wound healing, their clinical translation is limited by suboptimal retention at the wound site. In this study, we developed a bioadhesive polydopamine − hyaluronic acid (PDA-HA) double network hydrogel via a facile one-step synthesis. The pristine PDA-HA hydrogel demonstrated an intrinsic capacity to mitigate high glucose-induced endothelial dysfunction in vitro. Furthermore, the PDA-HA loaded with exosomes (PDA-HA@Exo) utilized its tissue adhesiveness to synergistically promote diabetic wound healing with sustained exosome release. In the murine full-thickness diabetic wound model, PDA-HA@Exo treatment markedly accelerated re-epithelialization, optimized collagen remodeling, stimulated angiogenesis, and suppressed inflammatory responses with polarizing macrophages from a pro-inflammatory M1 to a reparative M2 phenotype. Collectively, these findings highlight PDA-HA@Exo as a promising therapeutic strategy for diabetic wound management, effectively addressing exosome application challenges and offering potential for broader regeneration applications.