Mesenchymal Stem Cell-Inspired Microneedle Platform for NIR-responsive Immunomodulation and Accelerated Chronic Wound Healing.

IF 26.8 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Chan Ho Moon,Hee Gyeong Ko,Hyun Lee,Seojoon Bang,Hyeong Seok Kang,Ju Yeong Gwon,Jong Hwa Seo,Nayoung Lee,So Won Jeon,Yun-A Kim,Jong Sang Yoon,Kyung-Yup Cha,Min-Ho Kang,Dong Yun Lee,Soo-Hong Lee,Gi Doo Cha,Kisuk Yang,Donghyun Lim,Heemin Kang,Su Ryon Shin,Han Young Kim,Hyun-Do Jung
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Abstract

Chronic diabetic wounds present substantial clinical challenges owing to sustained inflammation, compromised vascularization, and inadequate retention of therapeutic medications. Accordingly, motivated by mesenchymal stem cells (MSCs) that actively secrete bioactive exosomes in response to stimuli from the tissue microenvironment, a biomimetic microneedle (MN) platform (MSCi@MN) is created to address these challenges. The MSCi@MN exhibits a dual-compartment structure composed of MSC-derived extracellular nanovesicles (NV) conjugated with polydeoxyribonucleotide (PDRN; DNA), referred to as NV-DNA, encapsulated within dissolvable MN tips, and photothermal-responsive MXene nanoparticles (MX) incorporated into the base layer for targeted near-infrared (NIR)-activated drug delivery. Upon NIR irradiation, MSCi@MN quickly releases NV-DNA, effectively modifying the immune responses by facilitating anti-inflammatory M2 macrophage polarization and activating tolerogenic dendritic cells, thereby establishing a regenerative microenvironment. Transcriptomic research has verified that NV-DNA synergistically promotes angiogenesis, cellular proliferation, and extracellular matrix remodeling by activating complementary molecular pathways. In animal models of diabetes, MSCi@MNs markedly expedite wound repair, diminish inflammation, enhance angiogenesis, and restore skin appendages without systemic adverse effects. This MSC-inspired approach, which integrates biologically sensitive controlled release with robust immunoregenerative capabilities, has substantial potential for clinical use in chronic wound treatment and regenerative medicine.
间充质干细胞激发的nir反应性免疫调节微针平台和加速慢性伤口愈合。
慢性糖尿病伤口由于持续的炎症、血管受损和治疗药物的保留不足,呈现出实质性的临床挑战。因此,在响应组织微环境刺激而积极分泌生物活性外泌体的间充质干细胞(MSCs)的激励下,仿生微针(MN)平台(MSCi@MN)被创建来解决这些挑战。MSCi@MN具有双室结构,由msc衍生的细胞外纳米囊泡(NV)与聚脱氧核糖核酸(PDRN; DNA)结合组成,称为NV-DNA,封装在可溶解的MN针尖中,光热响应的MXene纳米颗粒(MX)结合在基层中,用于靶向近红外(NIR)激活的药物递送。在近红外照射下,MSCi@MN快速释放NV-DNA,通过促进抗炎M2巨噬细胞极化和激活耐受性树突状细胞有效地改变免疫反应,从而建立再生微环境。转录组学研究证实,NV-DNA通过激活互补的分子通路,协同促进血管生成、细胞增殖和细胞外基质重塑。在糖尿病动物模型中,MSCi@MNs显著加速伤口修复,减少炎症,促进血管生成,并恢复皮肤附属物,无全身不良反应。这种受msc启发的方法,结合了生物敏感的控制释放和强大的免疫再生能力,在慢性伤口治疗和再生医学方面具有巨大的临床应用潜力。
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
Advanced Materials
Advanced Materials 工程技术-材料科学:综合
CiteScore
43.00
自引率
4.10%
发文量
2182
审稿时长
2 months
期刊介绍: Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.
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