The effects of Nintedanib on muscle regeneration in a rat soft palate wound model

Following cleft palate surgery, muscle regeneration in the soft palate is often impaired by fibrosis, leading to speech problems. Nintedanib, an FDA-approved antifibrotic agent for idiopathic pulmonary fibrosis, may facilitate muscle regeneration by inhibiting the progression of fibrosis. This study evaluates the effects of Nintedanib in an in vivo rat soft palate wound model. A 1-mm full-thickness excisional wound was created, followed by daily systemic treatment with Nintedanib or control for 7 days. Tissue samples were collected at 3-, 7-, 28-, and 56-days post-surgery, and analyzed using AZAN staining (collagen and muscle) and immunostaining for MyHC (muscle), α-SMA (myofibroblasts), Pax7 (satellite cells), and ED1 (macrophages). At day 7, Nintedanib significantly reduced the percentage of myofibroblasts (33.5 ± 8.7%) compared to the control (63.6 ± 6.7%, p < 0.05), and decreased the percentage of macrophages (3.3 ± 0.8% vs. 5.7 ± 0.8%, p < 0.05). The density of satellite cells was significantly higher in the Nintedanib-treated group (91.2 ± 24.2 vs. 50.0 ± 12.6 cells/mm², p < 0.05) at day 28. The collagen area percentage was reduced in the Nintedanib-treated group at day 28 (70.3 ± 7.8% vs. 80.3 ± 6.2%, p < 0.05), but no significant difference at day 56. Moreover, muscle regeneration improved, evidenced by increased AZAN-stained muscle area at day 28 (29.7 ± 7.8% vs. 19.7 ± 6.2%, p < 0.05) and higher MyHC-positive area percentage at day 56 (32.3 ± 8.4% vs. 14.6 ± 11.3%, p < 0.05). Systemic Nintedanib treatment improves palatal muscle regeneration and temporarily reduces myofibroblast differentiation. However, the results on long-term fibrosis are unclear.