Effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride hydrogel in the repair of infected full-thickness skin defect wounds in mice

Gu Ya'nan; Xu Xianghao; Wang Yanping; Li Yutao; Liang Zhen; Yu Zhou; Peng Yizhi; Song Baoqiang

doi:10.3760/cma.j.cn501225-20231120-00201

Volume 40 Issue 2

Feb. 2024

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Article Navigation > CHINESE JOURNAL OF BURNS AND WOUNDS > 2024 > 40(2): 131-140

Gu YN,Xu XH,Wang YP,et al.Effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride hydrogel in the repair of infected full-thickness skin defect wounds in mice[J].Chin J Burns Wounds,2024,40(2):131-140.DOI: 10.3760/cma.j.cn501225-20231120-00201.

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Effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride hydrogel in the repair of infected full-thickness skin defect wounds in mice

doi: 10.3760/cma.j.cn501225-20231120-00201

1.
Xi'an Medical University, Xi'an 710021, China
2.
Department of Plastic Surgery, the First Affiliated Hospital, Air Force Medical University, Xi'an 710032, China
3.
Institute of Burn Research, State Key Laboratory of Trauma and Chemical Poisoning, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Chongqing 400038, China

Funds:

General Project of Science and Technology Department of Shaanxi Province of China 2020SF-179

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Corresponding author: Peng Yizhi, Email: yizhipengtmmu@163.com; Song Baoqiang, Email: songbq2012@163.com
Received Date: 2023-11-20
Available Online: 2024-02-26

Abstract

Abstract

Objective To investigate the effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride (GelMA) hydrogel (hereinafter referred to as composite hydrogel) in the repair of infected full-thickness skin defect wounds in mice. Methods This study was an experimental study. Cerium oxide nanoenzyme with a particle size of (116±9) nm was prepared by hydrothermal method, and GelMA hydrogel with porous network structure and good gelling performance was also prepared. The 25 μg/mL cerium oxide nanoenzyme which could significantly promote the proliferation of human skin fibroblasts and had high superoxide dismutase activity was screened out. It was added to GelMA hydrogel to prepare composite hydrogel. The percentage of cerium oxide nanoenzyme released from the composite hydrogel was calculated after immersing it in phosphate buffer solution (PBS) for 3 and 7 d. The red blood cell suspension of mice was divided into PBS group, Triton X-100 group, cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group, which were treated with corresponding solution. The hemolysis of red blood cells was detected by microplate reader after 1 h of treatment. The bacterial concentrations of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were determined after being cultured with PBS, cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h. The sample size in all above experiments was 3. Twenty-four 8-week-old male BALB/c mice were taken, and a full-thickness skin defect wound was prepared in the symmetrical position on the back and infected with MRSA. The mice were divided into control group without any drug intervention, and cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group applied with corresponding solution, with 6 mice in each group. The wound healing was observed on 3, 7, and 14 d after injury, and the remaining wound areas on 3 and 7 d after injury were measured (the sample size was 5). The concentration of MRSA in the wound exudation of mice on 3 d after injury was measured (the sample size was 3), and the blood flow perfusion in the wound of mice on 5 d after injury was observed using a laser speckle flow imaging system (the sample size was 6). On 14 d after injury, the wound tissue of mice was collected for hematoxylin-eosin staining to observe the newly formed epithelium and for Masson staining to observe the collagen situation (the sample size was both 3). Results After immersion for 3 and 7 d, the release percentages of cerium oxide nanoenzyme in the composite hydrogel were about 39% and 75%, respectively. After 1 h of treatment, compared with that in Triton X-100 group, the hemolysis of red blood cells in PBS group, GelMA hydrogel group, cerium oxide nanoenzyme group, and composite hydrogel group was significantly decreased ( P<0.05). Compared with that cultured with PBS, the concentrations of MRSA and Escherichia colicultured with cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h were significantly decreased ( P<0.05). The wounds of mice in the four groups were gradually healed from 3 to 14 d after injury, and the wounds of mice in composite hydrogel group were all healed on 14 d after injury. On 3 and 7 d after injury, the remaining wound areas of mice in composite hydrogel group were (29±3) and (13±5) mm ², respectively, which were significantly smaller than (56±12) and (46±10) mm ² in control group and (51±7) and (38±8) mm ² in cerium oxide nanoenzyme group (with P values all <0.05), but was similar to (41±5) and (24±9) mm ² in GelMA hydrogel group (with P values both >0.05). On 3 d after injury, the concentration of MRSA on the wound of mice in composite hydrogel group was significantly lower than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively (with Pvalues all <0.05). On 5 d after injury, the volume of blood perfusion in the wound of mice in composite hydrogel group was significantly higher than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively ( P<0.05). On 14 d after injury, the wound of mice in composite hydrogel group basically completed epithelization, and the epithelization was significantly better than that in the other three groups. Compared with that in the other three groups, the content of collagen in the wound of mice in composite hydrogel group was significantly increased, and the arrangement was also more orderly. Conclusions The composite hydrogel has good biocompatibility and antibacterial effect in vivo and in vitro. It can continuously sustained release cerium oxide nanoenzyme, improve wound blood perfusion in the early stage, and promote wound re-epithelialization and collagen synthesis, therefore promoting the healing of infected full-thickness skin defect wounds in mice.
- Biocompatible materials,
- Hydrogel,
- Infection,
- Cerium oxide nanoenzyme,
- Gelatin methacrylate anhydride,
- Wound repair

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References

[1]	GBD 2019 Antimicrobial Resistance Collaborators. Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019[J]. Lancet, 2022,400(10369):2221-2248. DOI: 10.1016/S0140-6736(22)02185-7.
[2]	ZhaoX, LiangY, HuangY, et al. Physical double-network hydrogel adhesives with rapid shape adaptability, fast self-healing, antioxidant and NIR/pH stimulus-responsiveness for multidrug-resistant bacterial infection and removable wound dressing[J].Adv Funct Mater, 2020, 30(17): 1910748. DOI: 10.1002/adfm.201910748.
[3]	BanuS,SurD.Role of macrophage in type 2 diabetes mellitus: macrophage polarization a new paradigm for treatment of type 2 diabetes mellitus[J].Endocr Metab Immune Disord Drug Targets,2023,23(1):2-11.DOI: 10.2174/1871530322666220630093359.
[4]	MarrellaA,LagazzoA,DellacasaE,et al.3D porous gelatin/PVA hydrogel as meniscus substitute using alginate micro-particles as porogens[J].Polymers (Basel),2018,10(4):380. DOI: 10.3390/polym10040380.
[5]	JiangG,LiS,YuK,et al.A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model[J].Acta Biomater,2021,128:150-162.DOI: 10.1016/j.actbio.2021.04.010.
[6]	RenS,ZhouY,ZhengK,et al.Cerium oxide nanoparticles loaded nanofibrous membranes promote bone regeneration for periodontal tissue engineering[J].Bioact Mater,2022,7:242-253.DOI: 10.1016/j.bioactmat.2021.05.037.
[7]	MaS,LuY,ZhuX,et al.Efficient modulation of electron pathways by constructing a MnO ₂-x@CeO ₂ interface toward advanced lithium-oxygen batteries[J].ACS Appl Mater Interfaces,2022,14(19):22104-22113.DOI: 10.1021/acsami.2c02318.
[8]	ChengX, ZhangX, SuD, et al. NO reduction by CO over copper catalyst supported on mixed CeO ₂ and Fe ₂O ₃: catalyst design and activity test[J]. Applied Catalysis B: Environmental, 2018, 239: 485-501.DOI: 10.1016/j.apcatb.2018.08.054.
[9]	EmaT,ChoiPG,TakamiS,et al.Facet-controlled synthesis of CeO ₂ nanoparticles for high-performance CeO ₂ nanoparticle/SnO ₂ nanosheet hybrid gas sensors[J].ACS Appl Mater Interfaces,2022,14(51):56998-57007.DOI: 10.1021/acsami.2c17444.
[10]	HosseiniM,MozafariM.Cerium oxide nanoparticles: recent advances in tissue engineering[J].Materials (Basel),2020,13(14):3072.DOI: 10.3390/ma13143072.
[11]	WangY,HuangY,FuY,et al.Reductive damage induced autophagy inhibition for tumor therapy[J].Nano Res,2023,16(4):5226-5236.DOI: 10.1007/s12274-022-5139-z.
[12]	MaiHX,SunLD,ZhangYW,et al.Shape-selective synthesis and oxygen storage behavior of ceria nanopolyhedra, nanorods, and nanocubes[J].J Phys Chem B,2005,109(51):24380-24385.DOI: 10.1021/jp055584b.
[13]	KarahanA,AAbbasoğluA,IşıkSA,et al.Factors affecting wound healing in individuals with pressure ulcers: a retrospective study[J].Ostomy Wound Manage,2018,64(2):32-39.
[14]	DunnillC,PattonT,BrennanJ,et al.Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process[J].Int Wound J,2017,14(1):89-96.DOI: 10.1111/iwj.12557.
[15]	LiuJ,HuF,TangJ,et al.Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling[J].Int J Mol Med,2017,39(4):879-888.DOI: 10.3892/ijmm.2017.2919.
[16]	LiangZ, LuoJ, LiuS, et al. Injectable, antibacterial, ROS scavenging and pro-angiogenic hydrogel adhesives promote chronic wound healing in diabetes via synergistic release of NMN and Mg ²⁺[J]. Chem Eng J, 2023, 475: 146092.
[17]	ThuHE,ZulfakarMH,NgSF.Alginate based bilayer hydrocolloid films as potential slow-release modern wound dressing[J].Int J Pharm,2012,434(1/2):375-383.DOI: 10.1016/j.ijpharm.2012.05.044.
[18]	ZhuM,LiuP,ShiH,et al.Balancing antimicrobial activity with biological safety: bifunctional chitosan derivative for the repair of wounds with Gram-positive bacterial infections[J].J Mater Chem B,2018,6(23):3884-3893.DOI: 10.1039/c8tb00620b.
[19]	KurianAG,SinghRK,PatelKD,et al.Multifunctional GelMA platforms with nanomaterials for advanced tissue therapeutics[J].Bioact Mater,2022,8:267-295.DOI: 10.1016/j.bioactmat.2021.06.027.
[20]	ZhouB,JiangX,ZhouX,et al.GelMA-based bioactive hydrogel scaffolds with multiple bone defect repair functions: therapeutic strategies and recent advances[J].Biomater Res,2023,27(1):86.DOI: 10.1186/s40824-023-00422-6.
[21]	NegutI,GrumezescuV,GrumezescuAM.Treatment strategies for infected wounds[J].Molecules,2018,23(9):2392.DOI: 10.3390/molecules23092392.
[22]	KorsvikC,PatilS,SealS,et al.Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles[J].Chem Commun (Camb),2007(10):1056-1058.DOI: 10.1039/b615134e.
[23]	AlsharifNB,SamuGF,SáringerS,et al.Antioxidant colloids via heteroaggregation of cerium oxide nanoparticles and latex beads[J].Colloids Surf B Biointerfaces,2022,216:112531.DOI: 10.1016/j.colsurfb.2022.112531.
[24]	KettigerH,SchipanskiA,WickP,et al.Engineered nanomaterial uptake and tissue distribution: from cell to organism[J].Int J Nanomedicine,2013,8:3255-3269.DOI: 10.2147/IJN.S49770.
[25]	YueK,Trujillo-de SantiagoG,AlvarezMM,et al.Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels[J].Biomaterials,2015,73:254-271.DOI: 10.1016/j.biomaterials.2015.08.045.
[26]	LeiK, SunY, SunC, et al. Fabrication of a controlled in situ forming polypeptide hydrogel with a good biological compatibility and shapeable property[J]. ACS Appl Bio Mater, 2019,2(4):1751-1761. DOI: 10.1021/acsabm.9b00157.
[27]	RamburrunP, KhanRA, ChoonaraYE. Design, preparation, and functionalization of nanobiomaterials for enhanced efficacy in current and future biomedical applications[J]. Nanotechnology Reviews, 2022, 11(1): 1802-1826.DOI: 10.1515/ntrev-2022-0106.
[28]	SorgH,TilkornDJ,HagerS,et al.Skin wound healing: an update on the current knowledge and concepts[J].Eur Surg Res,2017,58(1/2):81-94.DOI: 10.1159/000454919.
[29]	LiangY,HeJ,GuoB.Functional hydrogels as wound dressing to enhance wound healing[J].ACS Nano,2021,15(8):12687-12722.DOI: 10.1021/acsnano.1c04206.
[30]	LiY,BiX,WuM,et al.Adjusting the stiffness of a cell-free hydrogel system based on tissue-specific extracellular matrix to optimize adipose tissue regeneration[J/OL].Burns Trauma,2023,11:tkad002[2024-01-25].https://pubmed.ncbi.nlm.nih.gov/36873282/. DOI: 10.1093/burnst/tkad002.
[31]	HanZ,DengL,ChenS,et al.Zn ²⁺-loaded adhesive bacterial cellulose hydrogel with angiogenic and antibacterial abilities for accelerating wound healing[J/OL].Burns Trauma,2023,11:tkac048[2024-01-25].https://pubmed.ncbi.nlm.nih.gov/36751362/.DOI: 10.1093/burnst/tkac048.

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Effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride hydrogel in the repair of infected full-thickness skin defect wounds in mice

doi: 10.3760/cma.j.cn501225-20231120-00201