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<p>Keloids are refractory fibroproliferative disorders. Their treatment faces multiple clinical challenges, including the coexistence of multiple pathological mechanisms, low drug bioavailability, and keloid-related pruritus. This study developed an UV-responsive cross-linked hydrogel (FZRL) using lipoic acid-grafted chitosan (LACS) as the matrix. The hydrogel encapsulates ZIF-8 nanoparticles loaded with 5-fluorouracil (5Fu, denoted as 5Fu@ZIF-8) and the local anesthetic ropivacaine. Before injection, the hydrogel exists as a liquid precursor. It can be precisely delivered to the area around keloids. Under mild UV irradiation, it rapidly cross-links into a stable hydrogel. This enables long-term local retention of 5Fu and ropivacaine, preventing premature drug leakage. In the weakly acidic microenvironment of keloids, FZRL hydrogel degrades specifically and releases 5Fu and ropivacaine on demand. A nude mouse keloid model with subcutaneous inoculation of human keloid fibroblasts (KFs) showed that FZRL hydrogel regulates the TGF-β/Smad pathway. It inhibits KFs proliferation and abnormal angiogenesis, modifies the extracellular matrix structure, and remodels the keloid microenvironment. After treatment, the average keloid volume was reduced by 54.7 ± 12.1%. At the same time, it significantly relieved itching-related scratching and irritable behaviors. In conclusion, FZRL hydrogel has dual delivery properties, including UV-responsive gelation and acid-responsive drug release. It synergistically achieves multi-target anti-keloid effects, as well as pruritus relief and analgesia. It provides a new minimally invasive treatment strategy for refractory keloids and has potential clinical translation value.</p> Graphical Abstract <p></p>

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A multifunctional injectable nanocomposite hydrogel for precision keloid therapy via ECM remodeling and local pruritus relief

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月24日

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  • Jingyu Jin,
  • Chengjie Zhu,
  • Nuoya Wang,
  • Mingji Jin,
  • Yanxin Jin,
  • Heying Jin,
  • Shuang Zhang,
  • Yanhong Zhou,
  • Lei Zhao,
  • Yinli Luo,
  • Zhonggao Gao,
  • Zhehu Jin,
  • Shuangqing Wang

摘要

Keloids are refractory fibroproliferative disorders. Their treatment faces multiple clinical challenges, including the coexistence of multiple pathological mechanisms, low drug bioavailability, and keloid-related pruritus. This study developed an UV-responsive cross-linked hydrogel (FZRL) using lipoic acid-grafted chitosan (LACS) as the matrix. The hydrogel encapsulates ZIF-8 nanoparticles loaded with 5-fluorouracil (5Fu, denoted as 5Fu@ZIF-8) and the local anesthetic ropivacaine. Before injection, the hydrogel exists as a liquid precursor. It can be precisely delivered to the area around keloids. Under mild UV irradiation, it rapidly cross-links into a stable hydrogel. This enables long-term local retention of 5Fu and ropivacaine, preventing premature drug leakage. In the weakly acidic microenvironment of keloids, FZRL hydrogel degrades specifically and releases 5Fu and ropivacaine on demand. A nude mouse keloid model with subcutaneous inoculation of human keloid fibroblasts (KFs) showed that FZRL hydrogel regulates the TGF-β/Smad pathway. It inhibits KFs proliferation and abnormal angiogenesis, modifies the extracellular matrix structure, and remodels the keloid microenvironment. After treatment, the average keloid volume was reduced by 54.7 ± 12.1%. At the same time, it significantly relieved itching-related scratching and irritable behaviors. In conclusion, FZRL hydrogel has dual delivery properties, including UV-responsive gelation and acid-responsive drug release. It synergistically achieves multi-target anti-keloid effects, as well as pruritus relief and analgesia. It provides a new minimally invasive treatment strategy for refractory keloids and has potential clinical translation value.

Graphical Abstract