Antifibrotics for Cleft Palate Muscle Repair

Children born with a cleft lip and palate often need soft palate surgery. Although essential, this procedure can cause scarring that impairs muscle function, leading to speech and swallowing problems. This thesis investigated new strategies to limit such scarring and improve muscle healing, focusing on two antifibrotic approaches: Nintedanib and several TGF-β receptor I inhibitors. In vitro, these drugs effectively blocked myofibroblast formation and enhanced muscle cell growth. In rats, however, systemic Nintedanib caused side effects and did not prevent long-term scarring. Among the TGF-β-receptor I inhibitors, Galunisertib was the most promising, reducing fibrotis while supporting muscle regeneration. The thesis also reviews emerging stem cell and extracellular vesicle-based therapies, which may offer safer ways to improve healing with fewer side effects. Future research will focus on local drug delivery and testing in more advanced models to enable translation to clinical care.