LAUSR

BACKGROUND Rotator cuff healing is improved by reconstructing the fibrocartilaginous structure of the tendon-to-bone enthesis. Fibroblast growth factor (FGF)-18 (sprifermin) is a well-known growth factor that improves articular cartilage repair via its anabolic effect. This study aimed to investigate the effect of recombinant human FGF-18 (rhFGF-18) on the chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro and tendon-to-bone healing in a rat model of rotator cuff repair. METHODS Histological and reverse transcription-quantitative real-time polymerase chain reaction analyses of chondral pellets cultured with different concentrations of rhFGF-18 were performed. Bilateral detachment and repair of the supraspinatus tendon were performed on rats. The rats were administered 0.2 mL sodium alginate (SA) hydrogel with (rhFGF-18/SA group, n = 12) or without (SA group, n = 12) 20 μg rhFGF-18 into the repaired side. The simple repair group (n = 12) served as a control. At 4 and 8 weeks post-surgery, histological analysis and biomechanical tests were performed. RESULTS After chondrogenesis induction, compared with the control group, 10ng/mL rhFGF-18 increased pellets volume significantly (P = 0.002), with improved histological staining. It was noted that 10 ng/mL rhFGF-18 upregulated the mRNA expression (relative ratio to control) of aggrecan (2.59 ± 0.29, P < 0.001), SRY-box transcription factor 9 (1.88 ± 0.05, P < 0.001), and type II collagen (1.46 ± 0.18, P = 0.009). At 4 and 8 weeks post-surgery, more fibrocartilage and cartilaginous extracellular matrix was observed in rhFGF-18/SA-treated rats. The semiquantitative data from picrosirius red staining test were 31.1 ± 4.5 vs. 61.2 ± 4.1 at 4 weeks (P < 0.001) and 61.5 ± 2.8 vs. 80.5 ± 10.5 at 8 weeks (P = 0.002) (control vs. rhFGF-18/SA). Ultimate failure load (25.42 ± 3.61 N vs. 18.87 ± 2.71 N at 4 weeks and 28.63 ± 5.22 N vs. 22.15 ± 3.11 N at 8 weeks; P = 0.006 and P = 0.03, respectively) and stiffness (18.49 ± 1.38 N/mm vs. 14.48 ± 2.01 N/mm at 8 weeks, P = 0.01) were higher in the rhFGF-18/SA group than in the control group. CONCLUSION rhFGF-18 promoted chondrogenesis in the hBMSCs in vitro. rhFGF-18/SA improved tendon-to-bone healing in the rats by promoting regeneration of the fibrocartilage enthesis. rhFGF-18 (sprifermin) may be beneficial for improving tendon-to-bone healing after rotator cuff repair.