Vancomycin-Loaded Polycaprolactone Electrospinning Nanofibers Modulate the Airway Interfaces to Restrain Tracheal Stenosis.

Chuan Tian,Zijian Wang,Xueliang Zhou,Kexing Feng,Zhaonan Li,Yanan Zhao,Xinwei Han,Kunpeng Wu

doi:10.3389/fbioe.2021.760395

Abstract

Site-specific release of therapeutics at the infected trachea remains a great challenge in clinic. This work aimed to develop a series of vancomycin (VA)-loaded polycaprolactone (PCL) composite nanofiber films (PVNF-n, n = 0, 1, and 5, respectively) via the electrospinning technique. The physiochemical and biological properties of PVNF-n were evaluated by a series of tests, such as FT-IR, XRD, SEM-EDS, and antibacterial assay. The PVNF-n samples displayed a typical network structure of fibers with random directions. VA was successfully introduced into the PCL nanofibers and could be sustained and released. More importantly, PVNF-5 showed relatively good antibacterial activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae (SPn). Thus, PVNF-5 was covered onto the self-expandable metallic stent and then implanted into a New Zealand rabbit model to repair tracheal stenosis. Compared to a metallic stent, a commercial pellosil matrix–covered stent, and a PVNF-0–covered metallic stent, the PVNF-5–covered airway stent showed reduced granulation tissue thickness, collagen density, α-SMA, CD68, TNF-α, IL-1, and IL-6 expression. In conclusion, this work provides an anti-infection film–covered airway stent that in site restrains tracheal stenosis.

Highlights

Tracheal stenosis is usually caused by local or systemic inflammation, tuberculosis, and tumor
The characteristic peaks of PCL and VA were obviously presented in PVNF-0, PVNF-1, and PVNF-5, which indicated that VA was successfully introduced into the PCL nanofibers
The results suggested that PVNF-n could release VA in the airway for a long time, which played an important role in in-site inhibition of bacterial infection

Summary

Introduction

Tracheal stenosis is usually caused by local or systemic inflammation, tuberculosis, and tumor. It compromises the airstream, causing dyspnoea, and is even life-threatening in severe cases (Murgu et al, 2016). A variety of airway stents, such as the nickel–titanium alloy stent, silicone stent, 3D printing stent, and 125I stent, have been applied for tracheal stenosis (Dutau et al, 2015). These stents continue to stimulate hyperplasia of the granulation tissue and experience tracheal restenosis, and cannot meet the clinical needs (Ha et al, 2020). We speculated that bacterial infection might be an important factor leading to tracheal stenosis (Abbasidezfouli et al, 2009)

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