Glucose-responsive dynamic hydrogels from Agastache rugosa polysaccharide for diabetic wound healing.

A Glucose-Responsive Hydrogel with Multifunctional Properties for Accelerated Diabetic Wound Healing

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.

Click-crosslinked nano-hydrogel enables metabolic immune reprogramming for diabetic foot ulcers

Phototriggered adhesive hydrogels integrating Mg/Quercetin MOFs for synchronous regulation of inflammation and angiogenesis in diabetic wounds

Chronic wounds affect over 20% of diabetic patients, imposing substantial socioeconomic and personal burdens. The diabetic wound microenvironment is characterized by hyperglycaemia, oxidative stress, persistent inflammation, and vascular damage, which disrupt tissue homeostasis and significantly hinder healing. The development of innovative multifunctional hydrogels is essential for treating diabetic wounds within such complex microenvironments. Based on metal-organic framework nanomaterials, this study introduces a dual-network crosslinked adhesive GelNB/HAMA hydrogel incorporating magnesium ions and Quercetin-based metal-organic frameworks (denoted as MgQu@GelNB/HAMA). In vitro experiments revealed that Mg-quercetin metal-organic framework (MgQu) promotes macrophage polarization from M1 to M2 type, scavenges reactive oxygen species, and stimulates neovascularization. Photopolymerization technology is employed to solidify the hydrogel into a dressing, ensuring strong adhesion to the wound site and minimizing secondary tissue damage while facilitating sustained, controlled release of Quercetin and magnesium ions. In a dorsal wound model of diabetic mice, this in situ formed multifunctional hydrogel dressing effectively reduces excessive inflammation, enhances neovascularization, accelerates collagen tissue regeneration, and advances wound healing. By improving the pathological microenvironment of diabetes, this study presents a promising new strategy for diabetic wound repair.

Multifunctional pH-responsive HA-c-FZ1 hydrogel presents a promising therapeutic strategy for diabetic skin wounds

HA-c-FZ1 functions as a pH-responsive hydrogel dressing that combines peptide delivery and antimicrobial, redox-regulatory, immunomodulatory, and pro-angiogenic functions that positions it as a therapy for chronic diabetic wound repair by simultaneously addressing infection, inflammation, oxidative stress, and vascular regeneration.

Hyaluronic Acid-Based Hydrogel with a Glucose-Responsive ROS Scavenging Ability for Diabetic Wound Healing.

Findings indicated that glucose-responsive antioxidant modulation using HA-based hydrogels can be a useful approach for managing oxidative stress in chronic diabetic wounds.

A Tissue-Homologous Keratin-PBA Hydrogel Integrating Rationally Designed Nanomicelles Enables Microenvironment-Adaptive Repair of Chronic Diabetic Wounds.

Chronic diabetic wounds require continuous modulation of the hyperglycemia-induced pathological microenvironment. Although glucose-responsive biomaterials show promise for diabetic wound treatment, intelligent wound management with tissue specificity and multifactorial repair capacity remains urgently needed. Here, we develop a tissue-homologous, glucose-responsive hydrogel based on epidermis-derived keratin functionalized with phenylboronic acid (Keratin-PBA), which is crosslinked with oxidized sodium alginate (OSA) to form a double-network hydrogel (cOK) and integrated with bioactive nanomicelles for adaptive wound microenvironment regulation. Co-assembled nanomicelles (OA-PG NMs), composed of oleanolic acid (OA) and propyl gallate (PG), exhibit glucose-triggered release and complementary bioactivities targeting oxidative stress, inflammation, macrophage polarization, angiogenesis, fibroblast behavior, antibacterial activity, and MMP regulation. Notably, OA promotes angiogenesis via the TGR5-Akt-eNOS-NO signaling pathway. The resulting cOK@NM hydrogel enables spatiotemporally controlled nanomicelle release and significantly accelerates diabetic wound healing in vivo, as evidenced by rapid wound closure, enhanced M2 macrophage polarization, robust neovascularization, improved collagen remodeling, reduced AGEs, broad-spectrum antibacterial effects against E. coli and S. aureus, and increased granulation tissue formation. This work presents a tissue-homologous, intelligently adaptive platform integrating intrinsic regenerative bioactivity with glucose-responsive therapeutic adaptability.