调节从植入物涂层中随需释放万科米辛,通过化学修改微球菌核酶敏感的寡核酸链接剂
Jordan D Skelly1, Feiyang Chen1, Shing-Yun Chang1
1Department of Orthopedics and Physical Rehabilitation, UMass Chan Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, United States.
ACS applied materials & interfaces
|July 31, 2023
概括
化学修饰的寡核酸结合剂提供向的康胺释放,以预防黄金葡萄球菌周围假肢感染,为传统治疗提供生物相容的替代方案.
科学领域:
- 生物材料科学 生物材料科学
- 整形外科手术 整形外科手术
- 传染病研究 传染病研究
背景情况:
- 由黄金葡萄球菌 (S. aureus) 引起的周围假肢感染是骨科手术中的严重并发症,通常需要具有挑战性的治疗.
- 目前的局部抗生素输送方法可能会因为高剂量的药物而导致抗生素耐药性.
- 现有的用于预防黄金色杆菌感染的植入物涂层使用对微球菌核酶 (MN) 敏感的寡核酸链接剂.
研究的目的:
- 设计一个改进的植入物涂层平台,以防止S. aureus周围假肢感染.
- 化学修改寡核酸链接剂以调节它们的稳定性和对MN的敏感性,以控制康素的释放.
- 在临床前模型中评估这些改性涂料的疗效和生物相容性.
主要方法:
- 通过2'-O-甲基化和酸 (PS) 替代物 (0PS,2PS,6PS) 修改了寡核酸结合剂.
- 修改后的链接器被用来将万科米辛连接到植入物涂层上.
- 评估了修改后链接器的稳定性和MN裂变动力学.
- 涂层在预防黄金色杆菌感染方面的有效性被评估在老鼠大腿管道模型中,在3个月内监测细菌负载和骨变化.
主要成果:
- 基酸修饰显著改变了寡核酸链体稳定性和MN裂变率.
- 6PS链接剂表现出增加的稳定性和持续的万科胺素释放.
- 0PS和2PS链接器能够快速,按需释放万科米辛,在老鼠模型中有效地根除金黄色细菌.
- 在接受治疗的动物中没有观察到细菌污染或不良的骨变化.
- 涂料表现出优异的生物相容性,抗生素剂量明显低于骨.
结论:
- 化学修饰的寡核酸链接剂可以对抗生素释放动力学进行可调节的控制,以防止S. aureus周围假肢感染.
- 这些修改后的涂层代表了骨科植入物的有希望的,生物相容的预防策略.
- 该平台可以调整,以应对与黄金菌感染相关的不同临床风险.
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