Total Flavonoids of Rhizoma drynariae Enhance Bone Marrow Mesenchymal Stem Cell-Mediated Tendon-Bone Healing by Promoting Tissue Regeneration, Angiogenesis, and Modulation of Cytokine Expression.

(1) Objective: This study aimed to investigate the synergistic effect and underlying mechanisms of Total Flavonoids of Rhizoma drynariae (TFRD) in combination with Bone Marrow Mesenchymal Stem Cells (BMSCs) in the repair of tendon-bone injuries. (2) Methods: The effects of TFRD on the proliferation and migration of BMSCs were assessed using CCK-8 and scratch assays, and its potential to promote osteogenic and chondrogenic differentiation was evaluated. Concurrently, the pro-angiogenic effect of TFRD on Human Umbilical Vein Endothelial Cells (HUVECs) was observed. In vivo, a rat model of Achilles tendon-bone injury was established and animals were divided into four groups: SHAM, Model, BMSCs, and BMSCs + TFRD. After an 8-week intervention, the level of functional recovery was evaluated through histological analysis, immunohistochemistry, serum biochemical analysis, and biomechanical testing. (3) Results: A concentration of 5.0 μg/mL TFRD significantly promoted the proliferation, migration, and differentiation of BMSCs and enhanced the tube formation capacity of HUVECs. In the BMSCs + TFRD group, histological analysis revealed well-organized collagen fibers, increased cartilage deposition, and an optimized tendon-bone interface (TBI) structure. Immunohistochemistry showed upregulated expression of COL I, COL II, and SOX-9, alongside downregulated VEGFA. Furthermore, serum IL-6 levels were decreased, while IL-10 and TGF-β levels were elevated. The biomechanical properties were also significantly improved in this group. (4) Conclusions: TFRD promotes tendon-bone healing and functional recovery by enhancing BMSC functions, promoting angiogenesis, and improving the local microenvironment.