摘要
背景:目前感染性骨缺损的治疗存在病程长、治疗效果不佳及花费较高等问题,并且临床治疗使用个性化骨替代材料的成骨作用有限,故临床治疗亟需一种兼具良好成骨效果和抗菌作用的3D打印植骨材料。目的:总结负载抗菌制剂3D打印支架用于感染性骨缺损的研究现状。方法:检索2010年1月至2022年6月PubMed、Web of Science、Elsevier及中国知网收录的相关文献,中文检索词为“骨缺损,3D打印,支架材料,抗菌,动物实验,体外实验”,英文检索词为“bone defect,3D printing,scaffold,antibiosis,animal experiment,in vitro”,最终纳入60篇文献进行综述分析。结果与结论:钛、镁、钽等金属及其合金制备的3D支架具备一定成骨性能,但不具备抗菌功能。羟基磷灰石等生物陶瓷材料的生物相容性好、易降解,但因强度不够通常与人工高分子聚合物材料结合成复合材料,分别模仿天然骨中的无机成分和有机成分,发挥各自优良功能。抗生素、纳米银/铜、抗菌肽、镓元素等抗菌制剂分别通过破坏细菌细胞膜、产生活性氧干扰细菌DNA复制、抑制铁元素吸收等机制来发挥抗菌作用,使3D打印支架兼具抗菌及成骨的双重作用,但目前仍存在耐药性及有效浓度难以控制等问题。3D打印支架常通过支架负载载药微球、支架表面制备抗菌涂层、抗菌制剂与支架材料混合打印等方法负载抗菌制剂,其中支架表面制备抗菌涂层的负载方式应用最为广泛、抗菌作用发挥也更稳定,然而针对抗菌制剂种类选择最为匹配的负载方式需进一步探讨总结。优化复合支架材料的机械性能、制备仿生骨支架材料,使其降解速度与感染性骨缺损中的骨重建速度相吻合是未来的研究方向。理想的抗菌制剂须通过多种抗菌机制发挥作用,期望通过较低抗菌浓度发挥良好抗菌作用是抗骨感染研究的热点。将抗菌制剂负载在支架表面后,抗菌制剂对局部微环境发生“智能化”反应达到可控释放,同时调控微环境成骨、血管化及免疫反应,是目前研究关注的焦点。
BACKGROUND:At present,the treatment of infected bone defects has the problems of long course of disease,poor treatment effect and high cost.The osteogenic effect of personalized bone replacement materials in clinical treatment is limited.Therefore,a 3D-printed bone graft material with both good osteogenic effect and antibacterial effect is urgently needed for clinical treatment.OBJECTIVE:To summarize the research status of 3D-printed scaffolds loaded with antimicrobial agents for the treatment of infected bone defects.METHODS:PubMed,Web of Science,Elsevier,and CNKI databases from January 2010 to June 2022 were searched for related articles.The Chinese search terms were“bone defect,3D printing,scaffold material,antibacterial,animal experiments,in vitro experiments”.English search terms were“bone defect,3D printing,scaffold,antibiosis,animal experiment,in vitro”.Finally,60 articles were included for review and analysis.RESULTS AND CONCLUSION:The 3D scaffolds made of titanium,magnesium,tantalum and other metals and their alloys have certain osteogenic properties,but do not have antibacterial function.Hydroxyapatite and other bioceramic materials have good biocompatibility and are prone to be degraded,whereas due to the lack of strength,they are usually combined with artificial polymer materials to form composite materials,which respectively mimic the inorganic and organic components in natural bone,and play their respective excellent functions.Antibiotics,silver/copper nanoparticles,antimicrobial peptides,gallium and other antibacterial agents play an antibacterial role by destroying bacterial cell membrane,producing reactive oxygen species to interfere with bacterial DNA replication,inhibiting iron absorption and other mechanisms.As a result,the 3D-printed scaffold has both antibacterial and osteogenic effects.However,there are still some problems such as drug resistance and difficult to control effective concentrations.3D-printed scaffolds are often loaded with antibacterial agents by loading drug-loaded microspheres on scaffolds,preparing antibacterial coating on the scaffold surface,and participating in joint 3D printing with drugs.The loading mode of antibacterial coating prepared on the scaffold surface is the most widely used,and its antibacterial effect is more stable.Nonetheless,the selection of the most suitable loading mode for antibacterial agents needs to be further discussed and summarized.It is a future research prospect to optimize the mechanical properties of composite scaffolds and prepare biomimetic bone scaffolds so that the degradation rate is consistent with the bone reconstruction rate in infected bone defects.The ideal antibacterial agents may play a role through a variety of antibacterial mechanisms,thus being expected to play a good antibacterial effect through low antibacterial concentration,which should be a hot spot of anti-bone infection research.After loading antibacterial agents on the surface of the scaffold,antibacterial agents can“intelligently”react to the local microenvironment,achieving controlled release,and regulating the osteogenesis,vascularization and immune response of the microenvironment,which is the focus of current research.
作者
董博
李效宇
李碧榕
李珍
王子璇
尹昭懿
孟维艳
Dong Bo;Li Xiaoyu;Li Birong;Li Zhen;Wang Zixuan;Yin Zhaoyi;Meng Weiyan(Department of Oral Implantology,Hospital of Stomatology,Jilin University,Changchun 130012,Jilin Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2024年第29期4685-4690,共6页
Chinese Journal of Tissue Engineering Research
关键词
感染性骨缺损
3D打印
支架
生物材料
抗菌
综述
infected bone defect
3D printing
scaffold
biomaterial
antibacterial
review
作者简介
第一作者:董博,男,1998年生,黑龙江省黑河市人,汉族,医师,主要从事3D打印支架在成骨和抗菌方面的应用研究,https://orcid.org/0009-0009-6984-9663;通讯作者:孟维艳,主任医师,吉林大学口腔医院口腔种植科,吉林省长春市130012。