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Endogenous stimuli-responsive separating microneedles to inhibit hypertrophic scar through remodeling the pathological microenvironment

Author

Listed:
  • Zhuo-Ran Yang

    (Huazhong University of Science and Technology (HUST))

  • Huinan Suo

    (Tongji Medical College, HUST)

  • Jing-Wen Fan

    (The Forth Military Medical University (FMMU))

  • Niannian Lv

    (Huazhong University of Science and Technology (HUST))

  • Kehan Du

    (Huazhong University of Science and Technology (HUST))

  • Teng Ma

    (Huazhong University of Science and Technology (HUST))

  • Huimin Qin

    (Huazhong University of Science and Technology (HUST))

  • Yan Li

    (Tongji Medical College, HUST)

  • Liu Yang

    (Tongji Medical College, HUST)

  • Nuoya Zhou

    (Tongji Medical College, HUST)

  • Hao Jiang

    (Huazhong University of Science and Technology (HUST))

  • Juan Tao

    (Tongji Medical College, HUST)

  • Jintao Zhu

    (Huazhong University of Science and Technology (HUST))

Abstract

Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.

Suggested Citation

  • Zhuo-Ran Yang & Huinan Suo & Jing-Wen Fan & Niannian Lv & Kehan Du & Teng Ma & Huimin Qin & Yan Li & Liu Yang & Nuoya Zhou & Hao Jiang & Juan Tao & Jintao Zhu, 2024. "Endogenous stimuli-responsive separating microneedles to inhibit hypertrophic scar through remodeling the pathological microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46328-2
    DOI: 10.1038/s41467-024-46328-2
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    References listed on IDEAS

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    1. Wei Chen & Rui Tian & Can Xu & Bryant C. Yung & Guohao Wang & Yijing Liu & Qianqian Ni & Fuwu Zhang & Zijian Zhou & Jingjing Wang & Gang Niu & Ying Ma & Liwu Fu & Xiaoyuan Chen, 2017. "Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    2. Neil C. Henderson & Florian Rieder & Thomas A. Wynn, 2020. "Fibrosis: from mechanisms to medicines," Nature, Nature, vol. 587(7835), pages 555-566, November.
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