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.
Zhihao Wang (1993) obtained his master’s degree in Oral and Maxillofacial Surgery at Qingdao University Affiliated Hospital. In 2021 he started with his PhD research as part of the Department of Dentistry, section Orthondontics and Craniofacial Biology, Radboud University Medical Center. Currently, he is working as a licensed attending dentist in China.