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<p>Endotracheal intubation is essential in clinical care but often exacerbates airway inflammation, fibrosis, and microbial dysbiosis, contributing to long-term complications. This study investigates how newly developed, coated endotracheal tubes (ETTs) modulate airway healing through localized therapeutic delivery in a swine model of laryngotracheal injury. Animals were intubated with uncoated, dexamethasone-coated, or composite-coated (dexamethasone + PEG hydrogel delivering siRNA against <i>smad3</i>) ETTs for 3, 7, or 14 days. Tissues were analyzed via mechanical testing, immunohistochemistry, ELISA, cytokine profiling, 16S rRNA sequencing, and microscopy. Therapeutic coatings induced region- and time-dependent alterations in airway stiffness and extracellular matrix composition, including remodeling of collagen IV, laminin, and elastin. Reduced nuclear pSMAD3 staining in composite-treated airways relative to uninjured controls provided supportive, indirect evidence of altered SMAD3 pathway activity following <i>smad3</i>-targeting siRNA delivery, although downstream TGF-β1 and collagen I expression did not significantly differ across treatment groups or over the time course. Composite-coated ETTs also promoted a temporal shift from pro-inflammatory (M1) toward reparative (M2) macrophage phenotypes and altered local cytokine profiles. Microbial community composition varied by coating type and duration, with treatment-associated changes in bacterial taxa and predicted metabolic pathways. Mucin composition also shifted over time, reflecting evolving epithelial responses during prolonged intubation. These findings demonstrate that localized therapeutic delivery influences interconnected mechanical, inflammatory, and microbial responses during airway healing and supports the development of multifunctional ETT coatings as a strategy to modulate post-intubation airway remodeling.</p><p></p>

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Therapeutic-delivering endotracheal tubes heal intubation injury via mucosal remodeling and disrupting the inflammation-microbiome-fibrosis triad

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月21日

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  • Gabriela Gonzales,
  • Ronit Malka,
  • Solaleh Miar,
  • Joo L. Ong,
  • Rena Bizios,
  • Gregory R. Dion,
  • Teja Guda

摘要

Endotracheal intubation is essential in clinical care but often exacerbates airway inflammation, fibrosis, and microbial dysbiosis, contributing to long-term complications. This study investigates how newly developed, coated endotracheal tubes (ETTs) modulate airway healing through localized therapeutic delivery in a swine model of laryngotracheal injury. Animals were intubated with uncoated, dexamethasone-coated, or composite-coated (dexamethasone + PEG hydrogel delivering siRNA against smad3) ETTs for 3, 7, or 14 days. Tissues were analyzed via mechanical testing, immunohistochemistry, ELISA, cytokine profiling, 16S rRNA sequencing, and microscopy. Therapeutic coatings induced region- and time-dependent alterations in airway stiffness and extracellular matrix composition, including remodeling of collagen IV, laminin, and elastin. Reduced nuclear pSMAD3 staining in composite-treated airways relative to uninjured controls provided supportive, indirect evidence of altered SMAD3 pathway activity following smad3-targeting siRNA delivery, although downstream TGF-β1 and collagen I expression did not significantly differ across treatment groups or over the time course. Composite-coated ETTs also promoted a temporal shift from pro-inflammatory (M1) toward reparative (M2) macrophage phenotypes and altered local cytokine profiles. Microbial community composition varied by coating type and duration, with treatment-associated changes in bacterial taxa and predicted metabolic pathways. Mucin composition also shifted over time, reflecting evolving epithelial responses during prolonged intubation. These findings demonstrate that localized therapeutic delivery influences interconnected mechanical, inflammatory, and microbial responses during airway healing and supports the development of multifunctional ETT coatings as a strategy to modulate post-intubation airway remodeling.