Sekar Amita, Inverardi Nicoletta, Lekkala Sashank, Thomson Andrew, Daesety Vikram, Trendafilova Darina, Tierney Peyton, Collins Jamie E, Muratoglu Orhun K, Oral Ebru
Harris Orthopaedics Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA.
Department of Orthopaedic Surgery, Harvard Medical School, Boston, MA 02115, USA.
Bioengineering (Basel). 2025 Feb 12;12(2):173. doi: 10.3390/bioengineering12020173.
Peri-prosthetic joint infection (PJI) is a major post-arthroplasty complication that warrants alternative antibacterial approaches to improve prophylaxis and treatment outcomes. Local administration of analgesics post-surgery is common. Recent studies have demonstrated the antimicrobial potential of analgesics and the feasibility of dual drug-eluting ultra-high molecular weight polyethylene (UHMWPE) for local antibacterial applications. However, the antibacterial mechanism of action is poorly understood, and the translational value of antimicrobial dual drug-loaded UHMWPE has not been evaluated. In this study, we utilized the Laurdan assay and gene expression analysis to demonstrate the antibacterial action of bupivacaine hydrochloride (BP) and tolfenamic acid (TA) against Furthermore, we incorporated BP and TA into UHMWPE at different weight concentrations and studied their longitudinal drug release and real-time antibacterial properties. The analgesics showed a significant effect on the bacterial membrane properties comparable to known antibiotics and regulated bacterial gene expression. For the dual drug-loaded UHMWPE, the drug release rate from BP/TA combinations was interestingly not a direct function of the loaded drug weight percent, potentially due to the hydrophobicity of TA and the interactions between the two drugs. Combinations of BP and TA at the higher total drug concentration (10 and 20%) showed a prolonged antibacterial effect against , with great potential for prophylactic use.
人工关节周围感染（PJI）是关节置换术后的一种主要并发症，需要采用替代抗菌方法来改善预防和治疗效果。术后局部使用镇痛药很常见。最近的研究表明了镇痛药的抗菌潜力以及双药洗脱超高分子量聚乙烯（UHMWPE）用于局部抗菌应用的可行性。然而，其抗菌作用机制尚不清楚，抗菌双药负载UHMWPE的转化价值也未得到评估。在本研究中，我们利用劳丹测定法和基因表达分析来证明盐酸布比卡因（BP）和托芬那酸（TA）对……的抗菌作用。此外，我们将BP和TA以不同重量浓度掺入UHMWPE中，并研究了它们的纵向药物释放和实时抗菌性能。这些镇痛药对细菌膜特性显示出与已知抗生素相当的显著作用，并调节细菌基因表达。对于双药负载的UHMWPE，BP/TA组合的药物释放速率有趣的是并非负载药物重量百分比的直接函数，这可能是由于TA的疏水性以及两种药物之间的相互作用。BP和TA在较高总药物浓度（10%和20%）下的组合对……显示出延长的抗菌作用，具有很大的预防性使用潜力。
