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  3. A multifunctional hydrogel loaded with two nanoagents improves the pathological microenvironment associated with radiation combined with skin wounds

A multifunctional hydrogel loaded with two nanoagents improves the pathological microenvironment associated with radiation combined with skin wounds

  • Acta Biomater. 2023 Jan 31;S1742-7061(23)00060-0. doi: 10.1016/j.actbio.2023.01.052.
Zhuoqun Fang 1,  Yicheng Lv 2,  Haoruo Zhang 1,  Yuxiang He 2,  Hangqi Gao 1,  Caixiang Chen 1,  Dezhi Wang 1,  Penghong Chen 1,  Shijie Tang 1,  Junjing Li 3,  Zhihuang Qiu 4,  Xian'ai Shi 2,  Liangwan Chen 5,  Jianmin Yang 6,  Xiaosong Chen 7
Affiliations

Affiliations

  • 1 Department of Plastic Surgery and Regenerative Medicine, Fujian Medical University Union Hospital, Fuzhou, 350001, China; Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, China; Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, 350001, China; Department of Stem Cell Research Institute, Fujian Medical University, Fuzhou, 350004, China.
  • 2 College of Biological Science and Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China; Fujian Key Laboratory of Medical Instrument and Pharmaceutical Technology, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China.
  • 3 Department of Plastic Surgery and Regenerative Medicine, Fujian Medical University Union Hospital, Fuzhou, 350001, China; Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, China; Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, 350001, China; Department of Breast Surgery, Quanzhou First Hospital of Fujian Medical University, Quanzhou, 362000, China.
  • 4 Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, 350001, China; Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
  • 5 Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, 350001, China; Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China. Electronic address: chenliangwan@fjmu.edu.cn.
  • 6 College of Biological Science and Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China; Fujian Key Laboratory of Medical Instrument and Pharmaceutical Technology, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China. Electronic address: jmyang@fzu.edu.cn.
  • 7 Department of Plastic Surgery and Regenerative Medicine, Fujian Medical University Union Hospital, Fuzhou, 350001, China; Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, China; Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, 350001, China. Electronic address: chenxiaosong74@163.com.
PMID: 36736645 DOI: 10.1016/j.actbio.2023.01.052
Abstract

Persistent oxidative stress and recurring waves of inflammation with excessive Reactive Oxygen Species (ROS) and free radical accumulation could be generated by radiation. Exposure to radiation in combination with physical injuries such as wound trauma would produce a more harmful set of medical complications, which was known as radiation combined with skin wounds (RCSWs). However, little attention has been given to RCSW research despite the unsatisfactory therapeutic outcomes. In this study, a dual-nanoagent-loaded multifunctional hydrogel was fabricated to ameliorate the pathological microenvironment associated with RCSWs. The injectable, adhesive, and self-healing hydrogel was prepared by crosslinking carbohydrazide-modified gelatin (Gel-CDH) and oxidized hyaluronic acid (OHA) through the Schiff-base reaction under mild condition. Polydopamine nanoparticles (PDA-NPs) and mesenchymal stem cell-secreted small extracellular vesicles (MSC-sEV) were loaded to relieve radiation-produced tissue inflammation and oxidation impairment and enhance cell vitality and angiogenesis individually or jointly. The proposed PDA-NPs@MSC-sEV hydrogel enhanced cell vitality, as shown by cell proliferation, migration, colony formation, and cell cycle and Apoptosis assays in vitro, and promoted reepithelization by attenuating microenvironment pathology in vivo. Notably, a gene set enrichment analysis of proteomic data revealed significant enrichment with adipogenic and hypoxic pathways, which play prominent roles in wound repair. Specifically, target genes were predicted based on differential transcription factor expression. The results suggested that MSC-sEV- and PDA-NP-loaded multifunctional hydrogels may be promising nanotherapies for RCSWs. STATEMENT OF SIGNIFICANCE: The small extracellular vesicle (sEV) has distinct advantages compared with MSCs, and polydopamine nanoparticles (PDA-NPs), known as the biological Materials with good cell affinity and histocompatibility which have been reported to scavenge ROS free radicals. In this study, an adhesive, injectable, self-healing, Antibacterial, ROS scavenging and amelioration of the radiation related microenvironment hydrogel encapsulating nanoscale particles of MSC-sEV and PDA-NPs (PDA-NPs@MSC-sEV hydrogel) was synthesized for promoting radiation combined with skin wounds (RCSWs). GSEA analysis profiled by proteomics data revealed significant enrichments in the regulations of adipogenic and hypoxic pathways with this multi-functional hydrogel. This is the first report of combining this two promising nanoscale agents for the special skin wounds associated with radiation.

Keywords

Extracellular vesicles; Hydrogel; Nanomedicine; Polydopamine nanoparticles; Radiation combined with skin wounds.

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