Jun 2026· International Journal of Biological Macromolecules· Vol 374, pp.
153216
· 0 citations· 47 references
Medicine
TL;DR
Overall, CBPP/PVA@HAs gel represents a promising therapeutic strategy for diabetic wounds by simultaneously regulating oxidative stress and inflammation.
Abstract
The characteristics of diabetic wounds include persistent oxidative stress, chronic inflammation, and impaired tissue regeneration, making effective treatment challenging. A multifunctional self-healing hydrogel was developed by co-grafting Bletilla striata polysaccharide (BSP) with 3-aminophenylboronic acid and polyvinyl alcohol (PVA) via dynamic borate ester bonds. The resulting CBPP/PVA@HAs gel exhibits rapid self-healing properties, sprayability, tissue adhesiveness, and good biocompatibility. In vitro studies demonstrated that the gel showed efficient photothermal antibacterial activity against E. coli, S. aureus, and MRSA, effectively scavenged intracellular reactive oxygen species (ROS), and promoted the polarization of RAW264.7 macrophages toward the anti-inflammatory M2 phenotype. In vivo experiments further demonstrated that the hydrogel significantly accelerated diabetic wound healing, promoted collagen deposition, angiogenesis, and tissue regeneration. Mechanistically, the hydrogel activated the Nrf2/HO-1 antioxidant pathway, reduced the pro-inflammatory cytokines TNF-α and IL-1β, and increased anti-inflammatory cytokines (IL-10) and reparative factors (TGF-β). Consequently, the hydrogel improved the inflammatory microenvironment by alleviating oxidative stress. Overall, CBPP/PVA@HAs gel represents a promising therapeutic strategy for diabetic wounds by simultaneously regulating oxidative stress and inflammation.
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
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.
A multifunctional hydrogel patch developed by chemically modifying chitosan with N-acetylsulfonyl chloride and forming a cross-linked network with polyvinylpyrrolidone (PVP) represents a promising multifunctional dressing for the effective management of infected wounds.
Insha Kakroo, Nayeema Gull, Insha Mehraj et al.· ACS Applied Bio Materials· 0 citations
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.
Xihao Wang, Jingting Huang, Chuipin Kong et al.· ACS Applied Materials and In...· 0 citations
Chronic diabetic wounds are associated with the excessive production of reactive oxygen species (ROS) under hyperglycemic conditions, which contribute to impaired tissue regeneration. In this study, we developed a dual-crosslinked hyaluronic acid (HA)-based hydrogel dressing with a glucose-responsive ROS-scavenging behavior. The hydrogel was composed of methacrylated HA-phenylboronic acid (HAMA-PBA) and HA-dopamine (HA-DA), forming a stable primary network through photocrosslinking and a dynamic secondary network via reversible boronate-catechol interactions. Under hyperglycemic conditions, the competitive binding of glucose to PBA modulates these dynamic interactions, enabling the glucose-responsive regulation of antioxidant activity. The resulting hydrogel exhibited mechanical properties suitable for wound dressing applications and showed good biocompatibility. Glucose-dependent ROS scavenging and enhanced keratinocyte migration were observed in vitro. In a mouse model of chronic diabetic wounds, hydrogel treatment was associated with accelerated wound closure accompanied by improved re-epithelialization and collagen organization compared with those in control groups. Overall, these 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, Chang Hee Min et al.· ACS Applied Bio Materials· 0 citations
Diabetic foot ulcers (DFUs) arise within a dysregulated wound microenvironment in which sustained inflammation, bacterial susceptibility, and excessive oxidative stress collectively impede tissue repair. To address these interrelated barriers, we developed an asiaticoside-loaded silk fibroin/hyaluronic acid composite hydrogel (ASHF) as a bioactive dressing that couples structural support with localized drug delivery. By optimizing the mass ratio of its components, the resulting hydrogel achieved an excellent balance among mechanical compliance, swelling capacity, tissue adhesion, water vapor transmission rate, and enzymatic degradation. In vitro experiments demonstrated that ASHF released asiaticoside in a two-stage manner, was well tolerated by fibroblasts, promoted cell migration, and inhibited Escherichia coli and Staphylococcus aureus. In vivo evaluation in a diabetic mouse model revealed that ASHF-treated wounds closed more rapidly and showed stronger collagen deposition, CD31-positive neovascularization, and re-epithelialization. Dual immunofluorescence staining demonstrated a significant reduction in M1 macrophages (CD68+/CD86+) and a concurrent increase in M2 macrophages (CD68+/CD206+), alongside favorable shifts in local cytokines (decreased IL-6 and increased IL-10). These findings indicate an effective transition of the local immune microenvironment from persistent inflammation toward a pro-reparative state. Transcriptomic analysis of wound tissues further indicated that ASHF intervention was associated with enrichment of glutathione-related metabolic programs and epidermal differentiation signatures, together with upregulation of key genes including Gstm3, Aox4, Hal, and Krt1. These results suggest that ASHF supports diabetic wound repair through coordinated regulation of redox balance, macrophage polarization, and tissue reconstruction, highlighting its potential as a multifunctional dressing for chronic diabetic wounds.
Xinyu Liu, Siyi Luo, Haiyang Zhang et al.· International Journal of Bio...· 0 citations