Mesoporous CuS functionalized hydrogel with hierarchical structure for synergistic photothermal antibacterial activity, strong bioadhesion and accelerated hemostasis in wound repair.
A pioneering near-infrared activated antibacterial EPLGA/OHADA@HMCuS hydrogel was formulated by doping hollow mesoporous copper sulfide (HMCuS) into the three-dimensional spatial network structure formed between gallic acid-modified ε-polylysine (EPL-GA) and dopamine-engineered and oxidized hyaluronic acid (OHADA) and showcased favorable biocompatibility, sustaining cellular viability.
Abstract
Bacterial infection impeded wound healing, causing significant discomfort and endangering the lives of patients. Overusing antibiotics to address such infections has spurred drug resistance in certain pathogenic bacteria. Hence, there is a pressing demand for a non-antibiotic-dependent versatile dressing to amplify on-site antibacterial efficacy, effectively averting wound infections, and fostering wound recovery. In this study, a pioneering near-infrared activated antibacterial EPLGA/OHADA@HMCuS hydrogel was formulated by doping hollow mesoporous copper sulfide (HMCuS) into the three-dimensional spatial network structure formed between gallic acid-modified ε-polylysine (EPL-GA) and dopamine-engineered and oxidized hyaluronic acid (OHADA). This hydrogel not only exhibited exceptional mechanical characteristics and tissue adhesion but also showcased favorable biocompatibility, sustaining cellular viability. The obtained EPLGA/OHADA@ HMCuS hydrogel not only demonstrated robust antibacterial activity against E. coli and S. aureus under laser irradiation but also exhibited a pronounced cell migration-promoting effect. In mouse models of tail amputation and liver injury, this hydrogel exhibited remarkable hemostatic capabilities and was also capable of substantially expediting wound healing in bacterial-infected wounds-bearing rats, as evidenced by its promotion of collagen deposition and angiogenesis, along with the downregulation of inflammatory factors. Hence, this multifunctional EPLGA/OHADA@HMCuS hydrogel stands out as a highly promising wound-assisting material, exhibiting broad potential for clinical application in the future management of infected wounds.
This work demonstrates a safe and effective strategy for combating MDR infections through the combined action of photothermal therapy and nanozyme catalysis, offering promising potential for clinical wound management.
Weiwei Zhang, Lixiang Fan, Xuanjun Zhang et al.· ACS Applied Materials and In...· 0 citations
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.
Xueyan Hou, Yanan Lu, Tenglong Xu et al.· ACS Applied Materials and In...· 0 citations
Diabetic skin injury is a serious clinical challenge due to impaired healing and infection. Here, we developed a sandcastle worm-inspired hydrogel featuring a phosphate-catechol-amine synergistic network based on a poly(acrylic acid-co-acrylamide) network, functionalized with dopamine-grafted cellulose nanofibers (DA-PCNF) and quaternized chitosan (QCS), to accelerate diabetic wound healing. The hydrogel exhibits strong tissue adhesion (78.82 ± 2.55 kPa) and broad-spectrum antibacterial activity (99.67% killing of Escherichia coli and 99.55% killing of Staphylococcus aureus in vitro). More importantly, it exhibits pH-responsive swelling and adhesion behaviors, maintaining robust adhesion under mildly acidic wound conditions while attenuating adhesion under neutral conditions to facilitate atraumatic dressing removal. Antioxidant assays indicated that the hydrogel exhibits scavenging activity against various free radicals with efficiencies ranging from 30% to 40%, attributable to the catechol groups. In vivo application of the hydrogel to infected diabetic wounds significantly accelerated healing (99.82%, on day 12 after Pseudomonas aeruginosa-infected wound formation), with reduced inflammation and enhanced tissue regeneration. These findings demonstrate that the catechol-nanocellulose/chitosan polymeric hydrogel effectively overcomes adhesion, infection, and oxidative stress barriers in diabetic wound healing, making it a promising candidate for difficult-to-heal chronic ulcers.
The application of adhesive hydrogels with phototherapy-based antibacterial properties has been extensively exploited in the repair of infected tissues. However, bacterial stress-adaptation may compromise the antibacterial efficacy of photothermal therapy. Herein, an injectable hydrogel by integrating aldehyde-functionalized hyaluronic acid modified by methacrylic anhydride (AHAMA) with recombinant human type III collagen (rhCol III)-modified molybdenum disulfide (MoS2) (namely AHAMA+rhCM hydrogel) was developed. rhCol III was cross-linked with AHAMA to form a double-network hydrogel that enhanced mechanical properties, as well as acting as a structural stabilizer of MoS2 to improve dispersion stability, ensuring photothermal conversion and effective antibacterial properties. According to an experimental study on Staphylococcus aureus (S. aureus)-infected wound healing, AHAMA+rhCM hydrogel under near-infrared (NIR) irradiation demonstrated the best wound healing efficiency in comparison to AHAMA and AHAMA+rhCM hydrogel without NIR exposure. This can be attributed to its potent antibacterial activity, attenuated inflammatory response, promoted angiogenesis, and optimized collagen deposition patterns, which collectively contributed to accelerated tissue regeneration and wound closure. In summary, the photothermal-driven AHAMA+rhCM hydrogel represents a promising therapeutic strategy for infected wound repair, offering a dual-action solution that integrates effective antibacterial properties with enhanced tissue regeneration capabilities.
Yafang Chen, Xue Zhan, Zhenyu Luo et al.· Small· 0 citations
Infected burn wounds are characterized by bacterial invasion, oxidative stress, and persistent inflammation, which severely impair tissue regeneration. Herein, we report a crosslinker-free, hydrogen-bonded cationic guar gum hydrogel (CBBM) co-loaded with berberine (BBR) and MnO2-coated black phosphorus nanosheets (BPNS@MnO2) for the microenvironment-adaptive treatment of infected burn wounds. The dynamic guar gum network endowed the hydrogel with injectability, self-healing ability, and conformal adaptability. BPNS@MnO2 exhibited pH-dependent enzyme-like activities, including OXD-like antibacterial activity under acidic conditions and SOD-/CAT-like ROS-scavenging activity under near-neutral conditions and endowed the hydrogel with NIR-triggered photothermal responsiveness. Moreover, NIR irradiation further enhanced the antibacterial efficacy and moderately enhanced BBR release from the hydrogel. In vitro, CBBM combined with NIR irradiation achieved potent antibacterial efficacy against S. aureus and E. coli under the tested conditions and reduced intracellular ROS levels. In vivo, the CBBM + NIR treatment accelerated infected burn wound healing, achieving a wound closure rate of 97.53 ± 2.01% by day 14, accompanied by reduced inflammation, enhanced collagen deposition, and increased expression of the angiogenesis-related markers VEGF and CD31. These results demonstrate that the CBBM hydrogel is a promising multifunctional guar gum-based dressing for infected burn wound healing by integrating local drug delivery, catalytic regulation, and photothermal activation.
Ziyi Zhao, Yanxiang Sang, Benyan Zheng et al.· International Journal of Bio...· 0 citations
The ability of hydrogels to promote wound healing has been extensively studied. Developing multifunctional hydrogel dressings to address the complex microenvironment of infected wounds remains a significant challenge and focus in current research. Herein, inspired by adhesion chemistry, we constructed a multifunctional composite hydrogel (GelDA/OPL) with excellent adhesion, self-healing properties, injectability, and photothermal antibacterial activity through Schiff base crosslinking between dopamine-modified gelatin (GelDA) and oxidized pullulan (OPL). By varying the concentration of OPL, the mechanical and rheological properties of GelDA/OPL can be appropriately adjusted. Furthermore, by introducing phycocyanin-modified CeO2@PC NPs, we endowed GelDA/OPL with remarkable antioxidant characteristics capable of rapidly scavenging ˙OH, ABTS˙+, and DPPH˙ radicals. The results indicate that the incorporation of catechol groups not only enhanced the adhesive performance of GelDA/OPL/CeO2@PC hydrogels but also imparted exceptional photothermal conversion efficiency under 808 nm laser irradiation, effectively inhibiting Staphylococcus aureus and Escherichia coli. The applicability of GelDA/OPL/CeO2@PC hydrogels in promoting wound healing in vivo was further validated using a full-thickness skin defect infection model in rats. Overall, the prepared GelDA/OPL/CeO2@PC hydrogel represents a promising multifunctional wound dressing that contributes to accelerating the healing process for infected wounds.
Chen Zhang, Surui Yang, Zhi Xu et al.· Journal of materials chemist...· 0 citations