In vitro and in vivo results demonstrate that the injectable dual-dynamic covalent hydrogel promotes macrophage polarization toward the anti-inflammatory M2 phenotype, alleviates inflammatory responses, enhances angiogenesis, and accelerates skin regeneration.
Abstract
Diabetic wounds are characterized by oxidative stress, chronic inflammation, and impaired tissue regeneration under persistent hyperglycemic conditions. Herein, we report an injectable dual-dynamic covalent hydrogel fabricated from phenylboronic-acid-functionalized oxidized sodium alginate and gallic-acid-conjugated chitosan. Crosslinked via reversible Schiff base and boronate ester bonds, the hydrogel exhibits excellent injectability, self-healing capability, and structural stability. Under hyperglycemic conditions, competitive glucose binding modulates the boronate ester equilibrium and induces glucose-responsive release of galloyl-containing species. These glucose-responsive release behaviors contribute to the antioxidant, antibacterial, and immunoregulatory activities of the hydrogel. In vitro and in vivo results demonstrate that the hydrogel promotes macrophage polarization toward the anti-inflammatory M2 phenotype, alleviates inflammatory responses, enhances angiogenesis, and accelerates skin regeneration. Collectively, the phenylboronic-acid-functionalized oxidized sodium alginate and gallic-acid-conjugated chitosan hydrogel represents a multifunctional glucose-responsive biomaterial with considerable potential for diabetic wound therapy.
Findings indicated that glucose-responsive antioxidant modulation using HA-based hydrogels can be a useful approach for managing oxidative stress in chronic diabetic wounds.
J. Hong, Min Ji Kim, Hee-Min Chang et al.· ACS Applied Bio Materials· 0 citations
A multifunctional hydrogel dressing was constructed from carboxymethyl chitosan and oxidized dextran as the dynamic network, incorporating CeO2 nanozymes for early anti-inflammatory and antioxidant effects and PLGA microspheres loaded with astragaloside IV for sustained pro-regeneration.
Xihao Wang, Jingting Huang, Chuipin Kong et al.· ACS Applied Materials and In...· 0 citations
This multifunctional hydrogel provides a promising strategy for diabetic wound management by integrating antibacterial potential and tissue regeneration by integrating antibacterial potential and tissue regeneration.
A precision-engineered hydrogel that integrates structural integrity with environment-triggered delivery and seamlessly coupling nanocontrolled release with microenvironmental sensing is presented, presenting a precision-engineered platform for the synergistic treatment of recalcitrant diabetic wounds.
A multifunctional, mechanism-targeted strategy that provides a rational, disease-relevant approach for treating chronic diabetic wounds by dampening inflammatory signaling and protecting reparative cells is developed.
Yuefei Zhu, Na Yan, Yongqiang Xiao et al.· Small· 0 citations
Diabetic wounds are characterized by excessive oxidative stress, persistent inflammation, and impaired tissue regeneration, which collectively hinder normal wound healing. Here, we developed a near-infrared (NIR)-responsive sodium alginate hydrogel incorporating nano‑iron sulfide (nFeS) through mild gelation mediated by calcium carbonate and glucono-δ-lactone. The resulting SA-nFeS hydrogel exhibited a porous structure, favorable rheological properties, hydrogen peroxide-responsive degradation, radical-scavenging activity, and good cytocompatibility. NIR irradiation accelerated the release of Fe from the hydrogel, increasing the cumulative release from approximately 35.5% to 75.4% over 48 h. In cells exposed to oxidative stress, the NIR-treated SA-nFeS hydrogel markedly reduced intracellular reactive oxygen species and promoted Nrf2 nuclear translocation, accompanied by decreased Keap1 expression and increased expression of the downstream antioxidant proteins HO-1, SOD1, SOD2, and GPX4. Furthermore, the hydrogel suppressed pro-inflammatory macrophage markers and cytokines while increasing the expression of CD206, Arg-1, and IL-10, indicating a shift toward a pro-healing macrophage phenotype. In a streptozotocin-induced diabetic full-thickness wound model, SA-nFeS combined with NIR irradiation achieved approximately 93% wound-area reduction by Day 14 and promoted re-epithelialization, granulation tissue formation, and collagen deposition. No obvious histopathological abnormalities were observed in the major organs. Collectively, these findings demonstrate that the NIR-responsive SA-nFeS hydrogel promotes diabetic wound repair by activating endogenous antioxidant defense and modulating the inflammatory microenvironment, providing a promising therapeutic platform for chronic wound management.
Xiaofang Wang, Jun Chen, Tingyi Guo et al.· International Journal of Pha...· 0 citations
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