The current evidence provides support for the involvement of bone marrow mesenchymal stem cells (BMSCs) in the regulation of airway epithelial cells. However, a comprehensive understanding of the underlying biological mechanisms remains elusive. This study aimed to isolate and characterize BMSC-derived exosomes (BMSC-Exos) and epithelial cells (ECs) through primary culture. Subsequently, the impact of BMSC-Exos on ECs was assessed in vitro, and sequencing analysis was conducted to identify potential molecular mechanisms involved in these interactions. Finally, the efficacy of BMSC-Exos was evaluated in animal models in vivo. In this study, primary BMSCs and ECs were efficiently isolated and cultured, and high-purity Exos were obtained. Upon uptake of BMSC-Exos, ECs exhibited enhanced proliferation (p < .05), while migration showed no difference (p > .05). Notably, invasion demonstrated significant difference (p < .05). Sequencing analysis suggested that miR-21-5p may be the key molecule responsible for the effects of BMSC-Exos, potentially mediated through the MAPK or PI3k-Akt signaling pathway. The in vivo experiments showed that the presence of methacrylated gelatin (GelMA) loaded with BMSC-Exos in composite scaffold significantly enhanced epithelial crawling in the patches in comparison to the pure decellularized group. In conclusion, this scheme provides a solid theoretical foundation and novel insights for the research and clinical application of tracheal replacement in the field of tissue engineering.