Tanshinone IIA / PCL nanofiber-covered airway stent inhibits tracheal stenosis

Mechanical injury is the primary initiating cause of iatrogenic tracheal stenosis (TS), while bacterial infection and persistent inflammatory responses are crucial exacerbating factors driving fibrotic progression. In this study, we constructed a Tanshinone IIA / PCL nanofiber-covered airway stent (PCL@Tan-IIA) using electrospinning technology. Characterizations revealed that the PCL@Tan-IIA stent possessed hydrophobic surface characteristics, favorable mechanical strength, and desirable drug-release kinetics, coupled with potent antibacterial efficacy against planktonic methicillin-resistant Staphylococcus aureus (MRSA). Mechanistically, the stent exerted anti-inflammatory activity by downregulating the secretion of pro-inflammatory cytokine IL-6 and upregulating the expression of anti-inflammatory cytokine IL-10 in macrophages. Concurrently, it exhibited anti-fibrotic effects through inhibiting the migration and activation of human pulmonary fibroblasts. Moreover, the PCL@Tan-IIA stent implanted in New Zealand rabbits inhibited local airway bacterial proliferation, alleviated inflammation and reduced excessive fibrous tissue hyperplasia. This work provides a promising strategy to overcome stent-induced restenosis and has potential for clinical translation in the management of TS.