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.
Abstract
Wound management, especially for infected and diabetic ulcers, poses a persistent clinical challenge, largely attributed to sustained inflammation, bacterial colonization, and compromised tissue regeneration. Herein, a multifunctional hydrogel (CBOS) with integrated therapeutic properties was developed through Schiff base reaction between betaine-modified chitosan (CSBT) and oxidized sodium alginate (OSA), with poly(vinyl alcohol) and sodium borate incorporated to enhance network stability. The resulting CBOS hydrogel exhibited a uniform porous microstructure, robust viscoelasticity, high swelling capacity, and appropriate water vapor transmission. Comprehensive biocompatibility assessments confirmed its negligible cytotoxicity and applicable hemocompatibility. The hydrogel demonstrated broad-spectrum tissue adhesion and potent hemostatic efficacy in murine tail incision and liver hemorrhage models. Moreover, CBOS displayed antioxidant activity by scavenging multiple free radicals and reducing intracellular reactive oxygen species in H2O2-stressed fibroblasts. Antibacterial evaluations revealed potent activity against S. aureus, with molecular docking studies suggesting multitarget interactions with key bacterial proteins, including AgrA, ClpP, and FtsZ. In vitro, CBOS significantly enhances fibroblast migration. In vivo, the hydrogel accelerated healing in both S. aureus-infected full-thickness wounds and diabetic chronic wounds, as evidenced by reduced bacterial burden, attenuated inflammatory responses, enhanced collagen deposition, and promoted neovascularization. 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.
Chronic infected wounds are often characterized by persistent bacterial colonization, biofilm formation, excessive oxidative stress, and prolonged inflammation, which severely impair tissue regeneration. To address these challenges, a multifunctional wound dressing capable of antibacterial activity and microenvironment modulation was developed. In this study, amide-modified hyaluronic acid (HA-ADH) was used as the matrix, and a dynamic coordination network was constructed via Cu2+-hydrazide interactions to form an in situ HA-Cu hydrogel. Curcumin-loaded DSPE-PEG2000 micelles were further incorporated to obtain a pH-responsive composite hydrogel (HA-Cu/Cur). The prepared hydrogel exhibited a porous interconnected structure, along with favorable injectability, self-healing capability, tissue adhesiveness, moderate swelling, controllable degradability, and pH-responsive behavior under acidic conditions. In vitro antibacterial assays demonstrated that both HA-Cu and HA-Cu/Cur effectively inhibited the growth and biofilm formation of Escherichia coli and Staphylococcus aureus. The antibacterial activity was associated with disruption of bacterial morphology, depletion of intracellular ATP, and induction of reactive oxygen species, while HA-Cu/Cur showed enhanced performance in antibiofilm activity and oxidative stress-related effects compared with HA-Cu. Cytocompatibility studies revealed that the hydrogel extracts exhibited negligible cytotoxicity toward L929 fibroblasts and RAW 264.7 macrophages, while promoting fibroblast migration and significantly reducing the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in lipopolysaccharide-stimulated RAW 264.7 cells, with HA-Cu/Cur showing a more pronounced anti-inflammatory effect. In summary, the HA-Cu/Cur hydrogel integrates the antibacterial and pro-healing properties of Cu2+ with the antioxidant and anti-inflammatory activities of curcumin. The hydrogel effectively inhibited the growth and biofilm formation of both E. coli and S. aureus, reduced the expression of TNF-α, IL-6, and IL-1β in LPS-stimulated macrophages, and promoted fibroblast migration, demonstrating its potential as a multifunctional wound dressing for the management of infected wounds.
Jiajie Chen, Haotian Huang, Yihan Wang et al.· Molecules· 1 citation
Hydrogel dressings have emerged as versatile platforms for wound management. However, effective treatment remains challenging due to complex wound environments involving hemorrhage, bacterial infection, and inflammation. Herei, a multifunctional pH-responsive hydrogel (PCOB 1) was developed via multinetwork cross-linking and freeze-thaw cycles using oxidized pullulan (OP), collagen, poly(vinyl alcohol) (PVA), and borax, and was impregnated with in situ stabilized silver nanoparticles (AgNPs). The incorporation of AgNPs endowed the hydrogel with pH-triggered antibacterial activity, achieving >99% killing of E. coli and S. aureus, efficient biofilm disruption, >90% ROS/RNS scavenging, and catalase-mimetic activity. The hydrogel demonstrated rapid gelation, self-healing, and hemostasis within 33.3 s. The hydrogel promoted macrophage polarization from M1 to M2, enhanced collagen deposition, re-epithelialization, and granulation tissue formation, achieving 98.5 ± 0.6% wound closure by day 14 in vivo. This study presents a multifunctional hydrogel with antibacterial, antioxidant, and anti-inflammatory properties for accelerated wound healing.
Muhammad Shahid, Mujahid Niaz, Huma Ghazal et al.· Biomacromolecules· 0 citations
Findings suggest that the synthesized hydrogel (BSG‐CHI) provides a favorable microenvironment for tissue regeneration and wound management applications.
Durgesh Kumar, Suhela Tyeb, Baby Shruit Shukla et al.· MedComm – Biomaterials and A...· 0 citations
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
Diabetic chronic wounds remain a major clinical challenge due to persistent infection, excessive inflammation, and impaired tissue regeneration. Herein, we report a multifunctional peptide-based antibacterial hydrogel (PAHG) for treating infected wounds, constructed through the incorporation of Cys-Arg-NH2 (CR)-Ag nanoassemblies into a bioactive matrix. In this design, the CR dipeptide enables in situ reduction and stable coordination of silver ions, yielding CR-Ag nanoassemblies with controlled silver release and enhanced biocompatibility. Co-assembly of this antibacterial component with chitosan, gelatin, collagen, and epidermal growth factor (EGF) affords a three-dimensional hydrogel network that provides a moist wound microenvironment, structural support, and sustained release of pro-regenerative cues. The resulting PAHG system exhibits excellent antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus, with inhibition efficiencies exceeding 80%, while maintaining high cytocompatibility with human skin fibroblasts (∼150% viability). In a diabetic infected wound model, PAHG significantly accelerates wound healing, achieving nearly complete closure within 12 days, accompanied by enhanced collagen deposition and no noticeable histopathological abnormalities in major organs. By integrating molecularly engineered antibacterial nanoassemblies with rationally designed multicomponent hydrogels, this work provides a promising strategy for the development of bio-based antimicrobial materials and chronic wound dressings.
Heng Ge, Wen Yuan, Yulin Sun et al.· Journal of materials chemist...· 0 citations