MiR‐141‐3p‐Functionalized Exosomes Loaded in Dissolvable Microneedle Arrays for Hypertrophic Scar Treatment

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 20; no. 8; pp. e2305374 - n/a
• Main Authors: Meng, Sheng, Wei, Qian, Chen, Shengqiu, Liu, Xi, Cui, Shengnan, Huang, Qilin, Chu, Ziqiang, Ma, Kui, Zhang, Wenhua, Hu, Wenzhi, Li, Shiyi, Wang, Zihao, Tian, Lige, Zhao, Zhiliang, Li, Haihong, Fu, Xiaobing, Zhang, Cuiping
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.02.2024
• Subjects: Arrays; Cell Proliferation - genetics; Cicatrix, Hypertrophic - genetics; Cicatrix, Hypertrophic - metabolism; Cicatrix, Hypertrophic - therapy; engineered exosomes; Eutrophication; Exosomes - metabolism; Fibroblasts; Fibroblasts - metabolism; Humans; hypertrophic scar; microneedle arrays; MicroRNAs - genetics; MicroRNAs - metabolism; miR‐141‐3p; Needles; Skin injuries; Stem cells; Sustained release; TGF‐β2/Smad pathway; Transforming Growth Factor beta2 - metabolism; Wound healing; microneedle arrays; engineered exosomes; fibroblasts; miR-141-3p; hypertrophic scar; TGF-β2/Smad pathway
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202305374

Hypertrophic scar (HS) is a common fibroproliferative disease caused by abnormal wound healing after deep skin injury. However, the existing approaches have unsatisfactory therapeutic effects, which promote the exploration of newer and more effective strategies. MiRNA‐modified functional exosomes delivered by dissolvable microneedle arrays (DMNAs) are expected to provide new hope for HS treatment. In this study, a miRNA, miR‐141‐3p, which is downregulated in skin scar tissues and in hypertrophic scar fibroblasts (HSFs), is identified. MiR‐141‐3p mimics inhibit the proliferation, migration, and myofibroblast transdifferentiation of HSFs in vitro by targeting TGF‐β2 to suppress the TGF‐β2/Smad pathway. Subsequently, the engineered exosomes encapsulating miR‐141‐3p (miR‐141‐3pOE‐Exos) are isolated from adipose‐derived mesenchymal stem cells transfected with Lv‐miR‐141‐3p. MiR‐141‐3pOE‐Exos show the same inhibitive effects as miR‐141‐3p mimics on the pathological behaviors of HSFs in vitro. The DMNAs for sustained release of miR‐141‐3pOE‐Exos are further fabricated in vivo. MiR‐141OE‐Exos@DMNAs effectively decrease the thickness of HS and improve fibroblast distribution and collagen fiber arrangement, and downregulate the expression of α‐SMA, COL‐1, FN, TGF‐β2, and p‐Smad2/3 in the HS tissue. Overall, a promising, effective, and convenient exosome@DMNA‐based miRNA delivery strategy for HS treatment is provided. A groundbreaking treatment for hypertrophic scar (HS) is within reach. Discoveries from this study reveal that miR‐141‐3p effectively inhibits HS fibroblasts. MiR‐141‐3pOE‐Exos, encapsulating miR‐141‐3p, exhibit the same effects. The application of dissolving microneedle arrays enables the sustained release of miR‐141‐3pOE‐Exos, resulting in decreased scar thickness and improved regenerative tissue characteristics. This delivery strategy holds immense potential to revolutionize HS treatment.