Chitosan nanoparticles-incorporated polylactic acid/tacrolimus nanofiber composite membrane for tracheal scar inhibition and tracheal wound healing promotion

Postoperative tracheal stenosis caused by excessive scar formation is a major complication of complex thoracic surgeries (e.g., sleeve lobectomy, lung transplantation) with limited effective preventive strategies. We hypothesized that a composite membrane integrating chitosan (CS), polylactic acid (PLA), and tacrolimus (TAC) via simultaneous electrospinning and electrospraying would inhibit tracheal scarring and promote tracheal wound healing by synergizing their respective advantages. Herein, we fabricated the CS nanoparticle-incorporated PLA/TAC nanofiber (CS/PLA/TAC) composite membrane and characterized its physicochemical properties (morphology, mechanical strength, wettability). In vitro, the membrane achieved sustained TAC release over 28 days, selectively promoting normal tracheal fibroblast proliferation, migration, invasion, and early collagen secretion, while suppressing hypertrophic scar fibroblast proliferation and collagen production by downregulating transforming growth factor-β and α-smooth muscle actin. It also exhibited strong antibacterial activity and good biocompatibility, which showed no significant liver or kidney impairment. In a mouse tracheal trauma model, the membrane effectively inhibited scar formation, regulated collagen deposition, and promoted normal tissue regeneration. These findings validate our hypothesis and highlight the CS/PLA/TAC composite membrane as a promising biomaterial for preventing postoperative tracheal stenosis and enhancing healing in clinical thoracic surgery.