TZU-HAO TSENGChen, Chien-LinChien-LinChenCHIH-HAO CHANGHONGSEN CHIANGJYH-HORNG WANGYoung, Tai-HorngTai-HorngYoung2025-05-082025-05-082025-03-06https://scholars.lib.ntu.edu.tw/handle/123456789/729068BACKGROUND: Antibiotic-loaded bone cement (ALBC) is crucial for treating orthopedic infections, but its use is limited by suboptimal antibiotic release patterns and potential toxicity. This study explores the dual addition of N-acetylcysteine (NAC) and vancomycin to polymethylmethacrylate (PMMA) as a strategy to enhance the antibacterial efficacy and reduce toxicity. METHODS: PMMA cement cylinders were loaded with varying combinations of NAC and vancomycin and tested for antibiotic release, cytotoxicity, and antibacterial activity over a 35-day period. Porosity of the cements was also evaluated as a measure of potential antibiotic release enhancement. RESULTS: The addition of NAC improved vancomycin release, particularly after the initial burst release phase, and reduced cytotoxicity compared to high-dose vancomycin alone. The optimal combination was found to be 2 gm vancomycin with either 2 gm or 4 gm of NAC, which maintained effective antibacterial activity over 35 days without the toxicity seen with higher doses of vancomycin alone. Moreover, NAC alone did not demonstrate antibacterial properties, indicating its role primarily as a bioenhancer in this context. CONCLUSION: Simultaneous inclusion of NAC and vancomycin in PMMA bone cement provides a more favorable release profile and biocompatibility than high-dose vancomycin alone, suggesting a potential strategy for enhancing the therapeutic efficacy of ALBC in treating prosthetic joint infections. This approach allows for lower doses of antibiotics, reducing potential cytotoxicity, systemic toxicity and enhancing the duration of antibacterial activity. LEVEL OF EVIDENCE: Laboratory study.enAntibiotic-loaded bone cementCytotoxicityN-acetylcysteinePMMAVancomycin[SDGs]SDG3journal article10.1186/s13018-025-05637-y40050926