Supplementary Material for: The Wound Healing of Autologous Regenerative Factor on Recurrent Benign Airway Stenosis: A Canine Experimental and Pilot Study

Introduction: Benign airway stenosis (BAS) is a severe pathologic condition. Complex stenosis has a high recurrence rate and requires repeated bronchoscopic interventions for achieving optimal control, leading to recurrent BAS (RBAS) due to intraluminal granulation. Methods: This study explored the potential of autologous regenerative factor (ARF) for treating RBAS using a post-intubation tracheal stenosis canine model. Bronchoscopic follow-ups were conducted, and RNA-seq analysis of airway tissue was performed. A clinical study was also initiated involving 17 patients with recurrent airway stenosis. Results: In the animal model, ARF demonstrated significant effectiveness in preventing further collapse of the injured airway, maintaining airway patency and promoting tissue regeneration. RNA-seq results showed differential gene expression, signifying alterations in cellular components and signaling pathways. The clinical study found that ARF treatment was well-tolerated by patients with no severe adverse events requiring hospitalization. ARF treatment yielded a high response rate, especially for post-intubation tracheal stenosis and idiopathic tracheal stenosis patients. Conclusion: The study concludes that ARF presents a promising, effective, and less-invasive method for treating RBAS. ARF has shown potential in prolonging the intermittent period and reducing treatment failure in patients with recurrent tracheal stenosis by facilitating tracheal mucosal wound repair and ameliorating tracheal fibrosis. This novel approach could significantly impact future clinical applications.

引言：良性气道狭窄（Benign Airway Stenosis, BAS）是一种严重的病理状态。复杂型气道狭窄复发率高，需反复实施支气管镜干预以实现最佳病情控制，最终因腔内肉芽组织增生引发复发性良性气道狭窄（Recurrent Benign Airway Stenosis, RBAS）。
方法：本研究借助插管后气管狭窄犬模型，探索自体再生因子（Autologous Regenerative Factor, ARF）治疗RBAS的潜力；研究过程中开展了支气管镜随访，并对气道组织进行RNA测序（RNA-seq）分析；同时启动了一项纳入17例复发性气道狭窄患者的临床研究。
结果：在动物模型中，ARF可有效阻止受损气道进一步塌陷、维持气道通畅并促进组织再生。RNA测序结果显示存在差异基因表达，提示细胞组分与信号通路发生改变。临床研究表明，ARF治疗耐受性良好，未出现需住院治疗的严重不良事件；且治疗应答率较高，尤其在插管后气管狭窄及特发性气管狭窄患者中效果显著。
结论：本研究证实，ARF是一种治疗RBAS极具前景、高效且微创的手段。ARF可通过促进气管黏膜创面修复、减轻气管纤维化，延长复发性气管狭窄患者的治疗间歇期并降低治疗失败风险。这一创新疗法有望对未来临床应用产生重大影响。