Abstract

Effective reprogramming of chronic wound healing remains challenging due to the limited drug delivery efficacy hindered by physiological barriers, as well as the inappropriate dosing timing in distinct healing stages. Herein, a core-shell structured microneedle array patch with programmed functions (PF-MNs) is designed to dynamically modulate the wound immune microenvironment according to the varied healing phases. Specifically, PF-MNs combat multidrug-resistant bacterial biofilm at the early stage via generating reactive oxygen species (ROS) under laser irradiation. Subsequently, the ROS-sensitive MN shell gradually degrades to expose the MN core component, which neutralizes various inflammatory factors and promotes the phase transition from inflammation to proliferation. In addition, the released verteporfin inhibits scar formation by blocking Engrailed-1 (En1) activation in fibroblasts. Our experiments demonstrate that PF-MNs promote scarless wound repair in mouse models of both acute and chronic wounds, and inhibit the formation of hypertrophic scar in rabbit ear models.

Effective reprogramming of chronic wound healing remains challenging due to the limited drug delivery efficacy hindered by physiological barriers, as well as the inappropriate dosing timing in distinct healing stages. Here, the authors report a core-shell structured microneedle array patch with programmed functions which dynamically modulates the wound immune microenvironment according to the varied healing phases

Details

Title
Scarless wound healing programmed by core-shell microneedles
Author
Zhang, Ying 1 ; Wang, Shenqiang 1   VIAFID ORCID Logo  ; Yang, Yinxian 1 ; Zhao, Sheng 1 ; You, Jiahuan 1 ; Wang, Junxia 1 ; Cai, Jingwei 2 ; Wang, Hao 1 ; Wang, Jie 3 ; Zhang, Wei 3 ; Yu, Jicheng 4 ; Han, Chunmao 3 ; Zhang, Yuqi 5   VIAFID ORCID Logo  ; Gu, Zhen 6   VIAFID ORCID Logo 

1  Zhejiang University, Key Laboratory for Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
2  Zhejiang University, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
3  Zhejiang University, Department of Burns and Wound Care Center, the Second Affiliated Hospital, College of Medicine, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
4  Zhejiang University, Key Laboratory for Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Jinhua Institute of Zhejiang University, Jinhua, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University Medical Center, Liangzhu Laboratory, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, National Key Laboratory of Advanced Drug Delivery and Release Systems, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
5  Zhejiang University, Key Laboratory for Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, Department of Burns and Wound Care Center, the Second Affiliated Hospital, College of Medicine, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, National Key Laboratory of Advanced Drug Delivery and Release Systems, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
6  Zhejiang University, Key Laboratory for Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Jinhua Institute of Zhejiang University, Jinhua, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University Medical Center, Liangzhu Laboratory, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, National Key Laboratory of Advanced Drug Delivery and Release Systems, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
Pages
3431
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-023-39129-6
ProQuest document ID
2825562224
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.