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一种可见光交联的促血管生成和抗炎的明胶甲基丙烯酰基(GelMA)微针阵列贴片,可共同释放一氧化氮和氧气用于糖尿病伤口愈合。

A visible light crosslinked angiogenic and anti-inflammatory GelMA microneedle array patch co-releasing nitric oxide and oxygen for diabetic wound healing.

作者信息

Ullah Asad, Zaidi Midhat Batool, Al Mamun Abdulla, Roome Talat, Hakim Saneea, Shin Su Ryon, Hasan Anwarul

机构信息

Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha, Qatar; Biomedical Research Center, Qatar University, Doha, Qatar.

Dow Institute for Advanced Biological & Animal Research, Dow University of Health Sciences, Karachi, Pakistan.

出版信息

Int J Biol Macromol. 2025 Jun 20;319(Pt 2):145450. doi: 10.1016/j.ijbiomac.2025.145450.


DOI:10.1016/j.ijbiomac.2025.145450
PMID:40545087
Abstract

Diabetic wounds are a major healthcare challenge, as their slow or impaired healing often leads to amputations and fatalities. Among the many factors contributing to the poor healing of diabetic wounds are insufficient angiogenesis and dysregulated inflammatory responses. Nitric oxide (NO) and oxygen (O) can be promising therapeutic agents to induce angiogenic and anti-inflammatory activities. In this study, we developed a visible light-crosslinked Gelatin Methacryloyl (GelMA) microneedle (MN) array patch capable of simultaneously delivering NO and O to diabetic wounds. The MN array patches were made based on micro molding technique using PDMS molds and visible light crosslinking based GelMA hydrogel. Scanning electron microscope (SEM) results revealed well-formed MNs with an average height of 650 μm. Under compression test, the MN array exhibited elastic behavior at forces below 150 mN per MN, which has been found to be adequate for penetration in human skin. In vitro degradation study in Phosphate buffered saline (PBS) solution revealed approximately 80 % degradation within 1 h, whereas in vivo degradation in rat skin tissue occurred at a slower rate, with around 50 % degradation after 24 h and complete dissolution observed after 48 h. In vitro cell proliferation assay indicated around 10 % increase in fibroblast proliferation and Scratch assay confirmed around 30 % higher cell migration with dual release MN array samples compared to control and blank samples. In vivo, the dual release MN array patches exhibited accelerated acute wound healing compared to untreated control group without showing any localized toxicity or inflammation over 14 days. Furthermore, diabetic wounds treated with the dual release MN array patches showed enhanced healing, confirmed by H&E and Masson's trichrome staining, along with reduced expression of inflammatory cytokine (TNF-α) and elevated expression of angiogenic (TGF-β) and anti-inflammatory (IL-10) biomarkers.

摘要

糖尿病伤口是一个重大的医疗保健挑战,因为其愈合缓慢或受损往往会导致截肢和死亡。导致糖尿病伤口愈合不良的众多因素中,血管生成不足和炎症反应失调是其中的原因。一氧化氮(NO)和氧气(O)有望成为诱导血管生成和抗炎活性的治疗剂。在本研究中,我们开发了一种可见光交联的甲基丙烯酰化明胶(GelMA)微针(MN)阵列贴片,能够同时向糖尿病伤口递送NO和O。MN阵列贴片是基于微成型技术,使用聚二甲基硅氧烷(PDMS)模具和基于可见光交联的GelMA水凝胶制成的。扫描电子显微镜(SEM)结果显示,微针形态良好,平均高度为650μm。在压缩测试中,MN阵列在每个微针低于150 mN的力作用下表现出弹性行为,已发现该力足以穿透人体皮肤。在磷酸盐缓冲盐水(PBS)溶液中的体外降解研究表明,1小时内降解约80%,而在大鼠皮肤组织中的体内降解速度较慢,24小时后降解约50%,48小时后观察到完全溶解。体外细胞增殖试验表明,与对照和空白样品相比,双释放MN阵列样品的成纤维细胞增殖增加约10%,划痕试验证实细胞迁移率高约30%。在体内,与未治疗的对照组相比,双释放MN阵列贴片显示出急性伤口愈合加速,在14天内未显示任何局部毒性或炎症。此外,用双释放MN阵列贴片治疗的糖尿病伤口愈合增强,经苏木精和伊红(H&E)染色和马松三色染色证实,同时炎症细胞因子(TNF-α)表达降低,血管生成(TGF-β)和抗炎(IL-10)生物标志物表达升高。

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