Mechanoregulative hydrogel facilitates rapid scarless healing by self-adaptive control of wound niche at different stages

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-05-23 DOI:10.1126/sciadv.adv9895

Haozhou Shu, Taotian Zhang, Yilin Jiang, Zhenkang Diao, Yani Xu, Jiaying Long, Tianyuan Chen, Mengxing Zhang, Zhirong Zhang, Junjie Chen, Shiqi Huang, Ling Zhang

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Abstract

It is essential to spatiotemporally control the microniche of wound at different healing stages for rapid and scarless healing. Hence, a multifunctional soft hydrogel integrated with programmed drug release capability (MLVgel) was fabricated. MLVgel is adhesive and moldable with low friction response, which provides moisture and responses to an infectious environment to deliver bactericidal and antioxidant effects in rat bacterial infection and burn wound models. By release control, instant short-term inflammation suppression is combined with sustained mechano-transduction signal inhibition. This dynamically modulates immune responses and delays En1⁺ fibroblast activation via the YAP-TEAD pathway, ultimately facilitating scarless wound regeneration. Genomic analyses showed that the enhanced reepithelization and mechanoregulation by MLVgel during different wound phases are indispensable for its therapeutic outcomes. Last, MLVgel resulted in markedly improved healing in a pig mature scar model, which demonstrated its translation potential. Our results also verified the necessity of programed dynamic regulation in the healing process.

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机械调节性水凝胶通过对不同阶段创面生态位的自适应控制，促进快速无疤痕愈合

在不同的愈合阶段，对伤口微微米的时空控制是快速无疤痕愈合的关键。因此，制备了一种具有程序释放能力的多功能软水凝胶（MLVgel）。MLVgel具有粘合性和可塑性，具有低摩擦反应，可提供湿度和对感染环境的反应，在大鼠细菌感染和烧伤伤口模型中提供杀菌和抗氧化作用。通过释放控制，即时短期炎症抑制与持续的机械转导信号抑制相结合。这通过YAP-TEAD途径动态调节免疫反应并延迟En1 +成纤维细胞激活，最终促进无疤痕伤口再生。基因组分析表明，MLVgel在不同伤口阶段增强的再上皮化和机械调节对其治疗效果是必不可少的。最后，MLVgel在猪成熟疤痕模型中显著改善了愈合，证明了其翻译潜力。我们的研究结果也证实了在愈合过程中进行程序化动态调节的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.