■小儿声门下狭窄(SGS)是由长时间插管引起的,其中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。在这里,我们展示了我们正在申请专利的抗菌肽洗脱气管导管(AMP-ET)如何有效调节局部气道微生物群,从而降低炎症和狭窄消退.
■我们制造了涂有聚合物AMP洗脱层的鼠标大小的ET,定量AMP释放超过10天,并验证了浮游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物(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LTC中,然后将其皮下植入受体小鼠体内,7天后评估免疫反应和SGS严重程度。
■我们实现了可重复的,以1.16µg/天的线性AMP释放,导致体外和离体强烈的细菌抑制作用。在体内,SGS诱导的LTC表现出典型的狭窄性瘢痕组织增厚,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浸润,用AMP-ET治疗逆转。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细胞应答解决狭窄进展。
■我们开发了一种AMP-ET平台,该平台通过气道微生物组调节在体内减少T细胞和巨噬细胞反应并减少SGS。
■在线版本包含补充材料,可在10.1007/s12195-023-00769-9获得。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: We developed an AMP-ET platform that reduces T cell and macrophage responses and reduces SGS in vivo via airway microbiome modulation.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12195-023-00769-9.