Aug 2026· ACS Applied Materials and Interfaces· 0 citations· 55 references
Medicine
TL;DR
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.
Abstract
Diabetic wound healingAC: remains challenging due to persistent inflammation, oxidative stress, and impaired macrophage polarization. Herein, 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. Via Schiff base crosslinking, this hydrogel self-assembled rapidly at room temperature and adhered tightly to tissue. In vitro, the hydrogel exhibited excellent biocompatibility, potent antioxidant and anti-inflammatory activities, and promoted endothelial cell migration and angiogenesis. In a diabetic rat full-thickness wound model, this hydrogel dressing effectively reduced local inflammation, drove macrophage polarization toward the M2 phenotype, and enhanced neovascularization to accelerate wound closure. RNA sequencing further revealed that inflammatory pathways, including TNF and IL-17 signaling, were suppressed while tissue regeneration programs were activated. This stepwise therapeutic strategy offers a promising alternative for diabetic wound repair.
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.
Zhao-Yun Wang, Susu Lei, Feng Lai et al.· Biomaterials Research· 0 citations
With its integrated hemostatic, antioxidant, antibacterial, and pro-regenerative properties, the CBOS hydrogel offers a viable and attractive therapeutic approach for complex wound tissue repair.
Xueyan Hou, Yanan Lu, Tenglong Xu et al.· ACS Applied Materials and In...· 0 citations
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.
Diabetic wounds exhibit prolonged inflammation and excessive oxidative stress, impairing tissue repair. Chronic hypoxia arises from vascular dysfunction and metabolic dysregulation, creating a pathological cycle of oxidative damage, defective angiogenesis, and persistent inflammation. To address these challenges, we develop the multifunctional rosmarinic acid-cerium nanozyme (RA-Ce NP) hydrogel composites designed for diabetic wound therapy. The system integrates RA-Ce NPs, phenylboronic acid-grafted poly-l-lysine, and oxidized hyaluronic acid into a dynamically crosslinked hydrogel network through Schiff base and boronate ester linkages. Both in vitro and in vivo studies demonstrate that the hydrogel enables multienzyme mimicry for synergistic reactive oxygen species scavenging, controlled oxygen generation to relieve tissue hypoxia, and promotion of neovascularization. Our work provides a clinically translatable platform for diabetic wound therapy, offering antibacterial, anti-inflammatory, and angiogenesis-promoting functions.
Junjie Wang, Zhijun You, Ling Zhou et al.· ACS Applied Materials and In...· 0 citations
Diabetic ulcers pose significant therapeutic challenges driven by hyperglycemia-induced oxidative stress, chronic inflammation, and microbial infection. While conventional dressings often fail to address these complex microenvironments, hydrogels have emerged as a premier platform for advanced wound management. Among these, chitosan-based hydrogels stand out for their intrinsic antimicrobial activity, biocompatibility, and tunable properties, enabling active orchestration of wound healing. Their therapeutic effects involve neutralizing oxidative stress, polarizing macrophages to resolve inflammation, and promoting angiogenesis for extracellular matrix remodeling. Moreover, these hydrogels can serve as multifunctional, stimuli-responsive platforms for the controlled delivery of drugs, growth factors, extracellular vesicles, nucleic acids, and even living cells, allowing precise spatiotemporal control of cargo release. This review summarizes the physicochemical properties of chitosan and systematically examines the molecular mechanisms underlying hydrogel-mediated diabetic wound repair. These include cation-mediated disruption of microbial membranes, Keap1/Nrf2-dependent antioxidant signaling, NF-κB-regulated immunomodulation, and VEGF-driven angiogenic pathways. In parallel, recent advances are critically evaluated in three key areas: stimuli-responsive delivery systems (triggered by pH, reactive oxygen species, matrix metalloproteinases, or glucose), biologically functionalized scaffolds incorporating extracellular vesicles, microRNAs, and stem cells, and 3D-bioprinted constructs tailored to individual patients. Current translational challenges are also addressed, particularly the complexity of regulatory classification and the lack of standardized preclinical models. Finally, future strategies are discussed for the rational design and clinical translation of next-generation diabetic wound dressings, with an emphasis on bridging the gap between bench research and bedside application.
Hongyun Chen, Ying Xin, Cheng-Kun Liu et al.· International Journal of Bio...· 0 citations
Chronic diabetic wounds remain a major clinical challenge owing to persistent bacterial infection, prolonged inflammation, excessive exudation, and impaired tissue regeneration. Herein, an injectable thermosensitive hydrogel was developed by integrating N-[(2-hydroxy-3-trimethylammonium)propyl] chitosan chloride with aldehyde-functionalized Pluronic F127 for epidermal growth factor (EGF) delivery and diabetic wound repair. The hydrogel forms a dual-crosslinked network through temperature-induced micellization and dynamic Schiff base bonding, exhibiting rapid gelation under physiological conditions, shear-thinning behavior, and self-healing properties. In vitro, the hydrogel provides a sustained release profile of EGF exhibiting effective antibacterial activity against Gram-positive S. aureus. In vivo studies in streptozotocin-induced diabetic rats demonstrate significantly accelerated wound healing, achieving 83% wound closure within 14 days compared to 45% in the control group, along with enhanced tissue regeneration characteristics, including improved collagen deposition. This multifunctional hydrogel provides a promising strategy for diabetic wound management by integrating antibacterial potential and tissue regeneration.