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

1. Nat Commun. 2024 Mar 6;15(1):2038. doi: 10.1038/s41467-024-46328-2.

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

Yang ZR(#)(1), Suo H(#)(2), Fan JW(3), Lv N(1), Du K(1), Ma T(1), Qin H(1), Li Y(2), Yang L(2), Zhou N(2), Jiang H(4), Tao J(5), Zhu J(6).

Author information: (1)Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China. (2)Department of Dermatology, Union Hospital, Tongji Medical College, HUST, Wuhan, 430022, China. (3)Department of Radiology, Xijing Hospital, The Forth Military Medical University (FMMU), Xi’an, 710032, China. (4)Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China. hustjh@hust.edu.cn. (5)Department of Dermatology, Union Hospital, Tongji Medical College, HUST, Wuhan, 430022, China. tjhappy@126.com. (6)Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China. jtzhu@mail.hust.edu.cn. (#)Contributed equally

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.

© 2024. The Author(s).

DOI: 10.1038/s41467-024-46328-2 PMCID: PMC10917775 PMID: 38448448 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.