Amelioration of Subglottic Stenosis by Antimicrobial Peptide Eluting Endotracheal Tubes.

IF 2.3 4区 医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2023-06-29 eCollection Date: 2023-08-01 DOI:10.1007/s12195-023-00769-9
Matthew R Aronson, Amrita Mehta, Ryan M Friedman, Daniel D Ghaderi, Ryan C Borek, Hoang C B Nguyen, Kendra S McDaid, Ian N Jacobs, Natasha Mirza, Riccardo Gottardi
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Abstract

Introduction: Pediatric subglottic stenosis (SGS) results from prolonged intubation where scar tissue leads to airway narrowing that requires invasive surgery. We have recently discovered that modulating the laryngotracheal microbiome can prevent SGS. Herein, we show how our patent-pending antimicrobial peptide-eluting endotracheal tube (AMP-ET) effectively modulates the local airway microbiota resulting in reduced inflammation and stenosis resolution.

Materials and methods: We fabricated mouse-sized ETs coated with a polymeric AMP-eluting layer, quantified AMP release over 10 days, and validated bactericidal activity for both planktonic and biofilm-resident bacteria against Staphylococcus aureus and Pseudomonas aeruginosa. Ex vivo testing: we inserted AMP-ETs and ET controls into excised laryngotracheal complexes (LTCs) of C57BL/6 mice and assessed biofilm formation after 24 h. In vivo testing: AMP-ETs and ET controls were inserted in sham or SGS-induced LTCs, which were then implanted subcutaneously in receptor mice, and assessed for immune response and SGS severity after 7 days.

Results: We achieved reproducible, linear AMP release at 1.16 µg/day resulting in strong bacterial inhibition in vitro and ex vivo. In vivo, SGS-induced LTCs exhibited a thickened scar tissue typical of stenosis, while the use of AMP-ETs abrogated stenosis. Notably, SGS airways exhibited high infiltration of T cells and macrophages, which was reversed with AMP-ET treatment. This suggests that by modulating the microbiome, AMP-ETs reduce macrophage activation and antigen specific T cell responses resolving stenosis progression.

Conclusion: We developed an AMP-ET platform that reduces T cell and macrophage responses and reduces SGS in vivo via airway microbiome modulation.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-023-00769-9.

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抗菌肽洗脱气管插管治疗声门下狭窄。
引言:儿童声门下狭窄(SGS)是由于长时间插管造成的,疤痕组织导致气道狭窄,需要进行侵入性手术。我们最近发现,调节喉气管微生物组可以预防SGS。在此,我们展示了我们正在申请专利的抗微生物肽洗脱气管插管(AMP-ET)如何有效调节局部气道微生物群,从而减少炎症和狭窄消退。材料和方法:我们制备了涂有聚合物AMP洗脱层的小鼠大小的ET,量化了10天内AMP的释放,并验证了浮游细菌和生物膜驻留细菌对金黄色葡萄球菌和铜绿假单胞菌的杀菌活性。离体测试:我们将AMP-ET和ET对照插入C57BL/6小鼠切除的喉气管复合体(LTCs)中,并在24小时后评估生物膜的形成。体内测试:将AMP ET和ET对照插入假手术或SGS诱导的LTCs中,然后将其皮下植入受体小鼠,并在7天后评估免疫反应和SGS严重程度。结果:我们以1.16µg/天的速度实现了可重复的线性AMP释放,从而在体外和离体产生了强烈的细菌抑制作用。在体内,SGS诱导的LTCs表现出典型的狭窄的增厚疤痕组织,而AMP-ET的使用消除了狭窄。值得注意的是,SGS气道表现出T细胞和巨噬细胞的高度浸润,AMP-ET治疗可逆转这种情况。这表明,通过调节微生物组,AMP-ET减少巨噬细胞活化和抗原特异性T细胞反应,从而解决狭窄进展。结论:我们开发了一种AMP-ET平台,通过气道微生物组调节来减少体内T细胞和巨噬细胞反应并减少SGS。补充信息:在线版本包含补充材料,可访问10.1007/s12195-023-00769-9。
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
CiteScore
5.60
自引率
3.60%
发文量
30
审稿时长
>12 weeks
期刊介绍: The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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