双膦酸盐药物复合支架在骨缺损局部的应用

Application of bisphosphonates incorporated into scaffolds in bone defects

背景:在骨缺损愈合过程中,将负载药物的生物材料植入缺损局部进行干预,可加速缺损的修复,这为骨缺损局部治疗提供了新的方法。目的:介绍负载双膦酸盐药物骨组织工程支架在骨缺损局部的应用,总结其对缺损愈合过程的影响。方法:作者以"bisphosphonates,alendronate,zoledronate,bone defect,bone tissue engineering;双膦酸盐,阿伦膦酸盐,唑来膦酸盐,骨缺损,骨组织工程"为关键词,检索2006至2018年期间PubMed、Web of Science、Springerlink、Medline、万方、CNKI数据库中发表的相关文献。初检文章235篇,筛选后对70篇文章进行分析。结果与结论:双膦酸盐药物是一种有效的破骨溶解抑制剂,其也可促进成骨细胞的增殖分化。将双膦酸盐药物负载于复合支架,可在缺损局部形成药物缓释系统,促进新骨形成,加速缺损的愈合。在双膦酸盐药物缓释系统方面,合适的支架材料对复合支架在缺损局部发挥成骨效应至关重要。目前应用于双膦酸盐药物复合支架的载体材料主要分为有机材料和无机材料2大类,其中大多数聚合有机材料可直接负载双膦酸盐药物,在局部形成良好的药物缓释,并可发挥明显的促进成骨效应;天然材料及大多无机材料则常与其他材料形成复合材料作为载体,从而优化载体的性能,大多数研究也证实了这些复合材料负载双膦酸盐药物在缺损局部的成骨作用。

BACKGROUND:In the process of bone defect healing,the use of biological materials loaded with drugs for local defect intervention can accelerate the repair of the defect,which provides a new method for the local treatment of bone defects.OBJECTIVE:To introduce the local application of bone tissue engineering scaffolds loaded with bisphosphonates in bone defect repair and to summarize the effects of bone tissue engineering scaffolds as a drug delivery system on the bone defect healing.METHODS:The authors retrieved PubMed,Web of Science,Springerlink,Medline,WanFang and CNKI databases with“bisphosphonates,alendronate,zoledronate,bone defect,bone tissue engineering”as key words for relevant articles published from 2006 to 2018.Initially,235 articles were retrieved,and finally 70 articles were selected for further analysis.RESULTS AND CONCLUSION:Bisphosphonate drug is an effective inhibitor of osteoclast dissolution.It can form a drug sustained release system on the local defect by being loaded to composite scaffolds,promote the formation of new bone and accelerate the healing of the defect.For the drug delivery system of bisphosphonates,suitable scaffold materials are crucial to the osteogenic effect of composite scaffolds in the defect area.At present,the carrier materials used for bisphosphonate-loaded composite scaffolds are mainly divided into organic materials and inorganic materials.Most polymeric organic materials can directly load bisphosphonates to form good drug sustained release in the local area and obviously exert their pro-osteogenic effects,while natural materials and most inorganic materials are often combined with other materials to form composite materials as carriers to optimize the carrier performance.Most studies have also confirmed that these composite materials loaded with bisphosphonates in the defect area exert osteogenic effect in the defect area.