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 <i>Rhizoma drynariae</i> (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.