Li Jinying, Hu Shi, Feng Pei, Xia Yang, Pei Zihan, Tian Jiaxuan, Jiang Kun, Liu Liang, Cai Xiong, Wu Ping
Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
State Key Laboratory of Precision Manufacturing for Extreme Service Performance, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China.
Polymers (Basel). 2024 May 17;16(10):1428. doi: 10.3390/polym16101428.
Bacterial infection is a common complication in bone defect surgery, in which infection by clinically resistant bacteria has been a challenge for the medical community. Given this emerging problem, the discovery of novel natural-type inhibitors of drug-resistant bacteria has become imperative. Brucine, present in the traditional Chinese herb , is reported to exert analgesic and anti-inflammatory effects. Brucine's clinical application was limited because of its water solubility. We extracted high-purity BS by employing reflux extraction and crystallization, greatly improved its solubility, and evaluated its antimicrobial activity against and . Importantly, we found that BS inhibited the drug-resistant strains significantly better than standard strains and achieved sterilization by disrupting the bacterial cell wall. Considering the safety concerns associated with the narrow therapeutic window of BS, a 3D BS-PLLA/PGA bone scaffold system was constructed with SLS technology and tested for its performance, bacteriostatic behaviors, and biocompatibility. The results have shown that the drug-loaded bone scaffolds had not only long-term, slow-controlled release with good cytocompatibility but also demonstrated significant antimicrobial activity in antimicrobial testing. The above results indicated that BS may be a potential drug candidate for the treatment of antibiotic-resistant bacterial infections and that scaffolds with enhanced antibacterial activity and mechanical properties may have potential applications in bone tissue engineering.
细菌感染是骨缺损手术中常见的并发症,其中临床耐药菌感染一直是医学界面临的挑战。鉴于这一新出现的问题,发现新型天然型耐药菌抑制剂已势在必行。马钱子碱存在于传统中药中,据报道具有镇痛和抗炎作用。由于其水溶性问题,马钱子碱的临床应用受到限制。我们采用回流提取和结晶法提取了高纯度的马钱子碱(BS),大大提高了其溶解度,并评估了其对[具体细菌1]和[具体细菌2]的抗菌活性。重要的是,我们发现BS对耐药菌株的抑制作用明显优于标准菌株,并通过破坏细菌细胞壁实现杀菌。考虑到与BS狭窄治疗窗相关的安全性问题,采用选择性激光烧结(SLS)技术构建了三维BS - PLLA/PGA骨支架系统,并对其性能、抑菌行为和生物相容性进行了测试。结果表明,载药骨支架不仅具有长期、缓慢控制释放且具有良好的细胞相容性,而且在抗菌测试中表现出显著的抗菌活性。上述结果表明,BS可能是治疗耐抗生素细菌感染的潜在药物候选物,具有增强抗菌活性和机械性能的支架在骨组织工程中可能具有潜在应用。