Abstract
Tracheal fistula (TF) is a severe thoracic disease characterized by high mortality rates, and current treatment methods present substantial risks while presenting challenges in reepithelialization. In this study, we developed a chimeric repairing patch (CRP) featuring a double-disc structure, designed to seal TF defects and promote organized tissue regeneration. The CRP incorporates a double-cross-linking silk fibroin network and hierarchical micropores, resulting in a flexible, hydrophilic, and biocompatible patch with tissue-matching mechanical properties. The CRP could effectively seal defects and encourage tissue ingrowth, successfully repairing TF. A tissue-engineered epithelialized CRP (E-CRP) was further developed to enhance in situ reepithelialization. The CRP demonstrated reliable structural stability and facilitated effective tissue regeneration and functional reconstruction of TF defects in a large animal model. Furthermore, the customized CRPs might be preloaded into a bronchoscope and precisely delivered to TF defects via noninvasive implantation. Consequently, the proposed CRP/E-CRP represents a promising scaffold for TF treatment, with substantial transformative potential in clinical practice.