| Summary: | Background: Injections of compound betamethasone (BT) combined with lidocaine (LD) have been applied for the treatment of rotator cuff tendinopathy; however, their effects on human rotator cuff tendon cells remain unknown. Purpose: To explore the cytocompatibility of BT and LD on degenerative human rotator cuff tendon cells. Study Design: Controlled laboratory study. Methods: BT and LD were diluted in cell culture medium (Dulbecco’s modified Eagle medium) to match their common clinical concentrations, and degenerative rotator cuff tendon cells were cultured with the drugs for 24 hours. Cell morphology and density were monitored for 21 days after the treatment. To identify the safe concentrations, the viability, apoptosis, proliferation, and cytoskeleton of tendon cells were investigated. An enzyme-linked immunosorbent assay was performed to analyze the influence of the selected concentrations on extracellular matrix expressions. Results: When treated with the common clinical concentrations of 0.7 mg/mL BT and 0.5% LD, or their combination, tendon cells exhibited significant changes in cell morphology, along with reduced cell viability. Higher concentration, particularly LD concentration, exacerbated these side effects. In contrast, treatment with lower concentrations of BT, LD, or their combination did not induce notable cytotoxicity or alterations in cell morphology and extracellular matrix composition, indicating a potential safety threshold for clinical application. Compared with the effects of BT or LD alone, the combination of BT and LD enhanced cytotoxicity, which was primarily driven by LD. Based on in vitro cytocompatibility assays, the relatively safe concentrations were determined to be 0.175 mg/mL for BT, 0.05% for LD, and a combination of 0.175 mg/mL BT + 0.025% LD. Conclusion: BT and LD demonstrate concentration-dependent cytotoxicity in degenerative rotator cuff tendon cells, with the combined treatment of BT and LD enhancing this effect, wherein LD plays a predominant role. The relatively safe concentrations for BT, LD, and their combination resulted in only transient alterations, with complete recovery of cell morphology and viability observed. Clinical Relevance: This finding can serve as a potential reference for the safer clinical application of BT and LD, especially in the treatment of degenerative rotator cuff tendinopathy.
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