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<p>Senescent mesenchymal stem cells residing in an inflammatory, dysbiotic, and hypoxic microenvironment pose a barrier to periodontal regeneration. Here we introduce a hydrocaffeic acid (HCA)-mediated silk fibroin hydrogel incorporating Mn/HCA-modified calcium peroxide (Mn-hCaO₂) and HCA-modified zeolitic imidazolate framework-8 (hZIF8) to rejuvenate this environment. The strategy imbues the hydrogel with enhanced adhesion and adaptability in periodontal pockets. The Mn-HCA complex acts catalytically to reduce oxidative stress and correct hypoxia. Simultaneously, Zn²⁺ and HCA restore microbial balance and mitigate inflammation. This multifunctional hydrogel targets the senescent periodontal niche by normalizing microbiota homeostasis and promoting a regenerative immune profile. Concurrently, it directly alleviates telomere shortening, DNA damage and oxidative stress in stem cells, thereby rejuvenating cellular function. By specifically addressing hypoxia and zinc deficiency, this polyphenol-mediated synergistic strategy offers a pathway to rejuvenate the senescent periodontal microenvironment, thereby overcoming tissue regeneration barriers and offering a translatable pathway for treating periodontitis and other aging-associated inflammatory diseases.</p>

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Polyphenol mediated zinc-oxygen synergistic hydrogel remodels senescent microenvironment for periodontal tissue regeneration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月10日

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  • Chengxinyue Ye,
  • Jin Liu,
  • Jinhui Ran,
  • Shoushan Hu,
  • Lu Yang,
  • Jialiang Zhao,
  • Xinyi Fang,
  • Zhenzhen Zhang,
  • Xin Xiong,
  • Xueman Zhou,
  • Yating Yi,
  • Xiaolong Zeng,
  • Xiong Lu,
  • Jun Wang,
  • Chaoming Xie

摘要

Senescent mesenchymal stem cells residing in an inflammatory, dysbiotic, and hypoxic microenvironment pose a barrier to periodontal regeneration. Here we introduce a hydrocaffeic acid (HCA)-mediated silk fibroin hydrogel incorporating Mn/HCA-modified calcium peroxide (Mn-hCaO₂) and HCA-modified zeolitic imidazolate framework-8 (hZIF8) to rejuvenate this environment. The strategy imbues the hydrogel with enhanced adhesion and adaptability in periodontal pockets. The Mn-HCA complex acts catalytically to reduce oxidative stress and correct hypoxia. Simultaneously, Zn²⁺ and HCA restore microbial balance and mitigate inflammation. This multifunctional hydrogel targets the senescent periodontal niche by normalizing microbiota homeostasis and promoting a regenerative immune profile. Concurrently, it directly alleviates telomere shortening, DNA damage and oxidative stress in stem cells, thereby rejuvenating cellular function. By specifically addressing hypoxia and zinc deficiency, this polyphenol-mediated synergistic strategy offers a pathway to rejuvenate the senescent periodontal microenvironment, thereby overcoming tissue regeneration barriers and offering a translatable pathway for treating periodontitis and other aging-associated inflammatory diseases.