AniView Supports Diabetic Wound Healing Research: Cerium dioxide nanozyme doped hybrid hydrogel with antioxidant and antibacterial abilities for promoting diabetic wound healing

New progress has been made in the development of cerium dioxide nanozyme-doped composite hydrogels for diabetic wound healing.

A research team led by Xiaokun Ouyang, Nan Wang, and Junhong Ling from the College of Food Science and Pharmacy, Zhejiang Ocean University, published their findings in the internationally renowned journal “Chemical Engineering Journal” (IF = 13.3, Q1 journal).

This study presents a multifunctional composite hydrogel with antioxidant, oxygen-generating, and antibacterial properties, offering a promising strategy for accelerating the healing of infected diabetic wounds.

Diabetic wounds, particularly diabetic foot ulcers, represent a major clinical challenge worldwide. Their complex pathological microenvironment severely impairs the wound-healing process. Due to prolonged hyperglycemia, diabetic patients continuously generate high levels of reactive oxygen species (ROS) at wound sites, accompanied by local hypoxia. These conditions not only exacerbate inflammation but also induce tissue damage, leading to delayed or chronic wound healing. Furthermore, the high-glucose environment makes wounds highly susceptible to bacterial infections, further aggravating tissue destruction and inflammatory burden. Although conventional wound dressings, such as hydrogels containing polyphenolic antioxidants, provide certain antioxidant benefits, their active components are often rapidly released, limiting long-term therapeutic efficacy. Therefore, there is an urgent need to develop a novel functional hydrogel capable of sustained antioxidant activity, effective antibacterial action, and alleviation of local hypoxia to create an integrated healing microenvironment for diabetic wounds.

In recent years, nanozymes have attracted increasing attention for the development of advanced antioxidant materials owing to their stable catalytic performance, tunable structures, and prolonged activity. Cerium dioxide nanoparticles (CeO₂ NPs), a representative nanozyme, exhibit remarkable catalase (CAT)- and superoxide dismutase (SOD)-like activities, enabling efficient ROS scavenging. Moreover, they can catalyze the decomposition of hydrogen peroxide into oxygen within the wound microenvironment, thereby alleviating local hypoxia. Incorporating antibacterial agents such as vancomycin can further enhance the therapeutic potential of these materials for infected diabetic wounds.

Based on these advantages, the researchers successfully designed and fabricated a composite hydrogel (PACV) loaded with CeO₂ nanoparticles and vancomycin, providing an effective solution for infected diabetic wound healing. Experimental results demonstrated that the PACV hydrogel possessed a stable three-dimensional porous structure, excellent water absorption and retention capacity, favorable flexibility, and strong tissue adhesion, enabling close contact with wound surfaces while maintaining a moist healing environment. The incorporation of CeO₂ NPs endowed the hydrogel with sustained ROS-scavenging capability, achieving a hydroxyl radical (·OH) removal rate of 85.40%, while simultaneously catalyzing the decomposition of H₂O₂ to generate oxygen and relieve local hypoxia. Meanwhile, the sustained release of vancomycin conferred potent antibacterial activity, with inhibition rates exceeding 90% against both Staphylococcus aureus and Pseudomonas aeruginosa.

In vitro studies confirmed that the PACV hydrogel exhibited excellent biocompatibility without cytotoxicity. It also promoted endothelial cell migration and effectively alleviated H₂O₂-induced oxidative stress. In an infected full-thickness diabetic wound model in mice, the PACV-treated group showed significantly faster wound healing than both the untreated control group and the commercial dressing group. The wound closure rate reached 86.44% on day 7 and approached complete healing by day 14. Histological analyses further revealed that PACV hydrogel treatment significantly reduced inflammation, promoted collagen deposition, enhanced angiogenesis, and decreased the expression of the hypoxia marker HIF-1α.

In summary, by integrating the antioxidant and oxygen-generating functions of CeO₂ nanoparticles with the antibacterial activity of vancomycin, the PACV hydrogel effectively remodels the pathological microenvironment of diabetic wounds. This multifunctional dressing offers a promising therapeutic strategy with strong clinical potential for the treatment of chronic diabetic wounds associated with infection and oxidative stress.

Experiments using Plantview

To evaluate the in vivo antioxidant performance of the PACV hydrogel, the researchers employed the AniView Multimodal In Vivo Imaging System developed by Guangzhou Biolight Biotechnology to dynamically monitor ROS levels in diabetic mouse wounds. Imaging results showed that ROS signals were detectable in all groups at the early stage of wound formation (day 2), indicating the onset of inflammatory responses. By days 4 and 6, ROS levels continued to increase in the untreated control group and the Comfeel® commercial dressing group, with markedly enhanced fluorescence intensity observed on day 4. These findings suggest that oxidative stress in diabetic wounds progressively worsens over time in the absence of effective intervention, thereby delaying wound healing.

In contrast, the PAC group (containing CeO₂ nanoparticles but no vancomycin) and the PACV group exhibited significantly reduced fluorescence intensity at day 4, confirming the strong ROS-scavenging capability of CeO₂ nanoparticles in vivo and their effectiveness in alleviating oxidative stress. Although the PA group (base hydrogel without CeO₂ nanoparticles or vancomycin) did not show a substantial increase in ROS levels, its ROS-scavenging performance was markedly inferior to that of the CeO₂ NP-containing groups.

DOI: 10.1016/j.cej.2024.154517