骨质疏松性骨缺损的治疗进展:支架植入与局部药物递送

摘要

背景:随着化学合成技术的发展,将抗骨质疏松药物纳入组织工程支架,用于促进骨质疏松性骨缺损骨再生已成为当今研究的热点.目的:介绍骨组织工程支架,讨论并总结其搭载抗骨质疏松药物在骨质疏松性骨缺损愈合方面的应用.方法:作者以"Osteoporosis,Bone defect,Scaffold,骨质疏松,骨缺损,支架"为关键词,检索2005至2017年期间PubMed、Web of Science、Springerlink、Medline、万方、CNKI数据库中相关文献.初检文章201篇,筛选后对64篇文章进行分析.结果与结论:各种类型的骨组织工程支架被用于治疗骨质疏松性骨缺损,如经过改性的磷酸钙骨水泥、β-磷酸三钙、羟基磷灰石等支架均起到一定促进骨再生的作用.但骨质疏松状态下的骨再生受损严重,常规支架促进骨再生能力有限,需要加以抗骨质疏松治疗.考虑到全身抗骨质疏松药物治疗不良反应大、骨缺损局部作用小的特点,近年来研究者对支架植入与局部药物递送相结合促进骨质疏松性骨缺损愈合进行了研究,如何将骨再生诱导因子纳入支架中,并稳定地从支架中释放而不影响其生物活性是关键.其中,双膦酸盐、金属锶、骨形态发生蛋白 2、甲状旁腺激素、中药成分、间充质干细胞作为常用药物,将其纳入凝胶中或通过涂层的方法与骨组织工程支架结合可达到缓释效果;随着分子生物技术的发展,经成骨相关基因修饰的干细胞复合支架也逐渐成为一个研究热点.%BACKGROUND: With the development of chemical synthesis technology, the application of anti-osteoporosis drugs incorporated into scaffolds to promote bone regeneration in osteoporotic bone defects has become a hot issue nowadays. OBJECTIVE: To introduce bone tissue engineering scaffolds, and to discuss and summarize the application of the scaffolds carrying anti-osteoporosis drugs for osteogenesis in osteoporotic bone defects. METHODS: PubMed, Web of Science, Springerlink, Medline, WanFang and CNKI databases were retrieved with "osteoporosis, bone defect, scaffold" as key words for relevant articles published from 2005 to 2017. Initially, 201 articles were retrieved, and finally 64 articles were selected for further analysis. RESULTS AND CONCLUSION: With the development of biochemical synthesis technology, various types of tissue-engineered bone scaffolds have been used for the treatment of osteoporotic bone defects. For example, the modified calcium phosphate cement, β-tricalcium phosphate, and hydroxyapatite all can promote bone regeneration. However, the ability of conventional scaffolds to promote bone regeneration is severely damaged under the state of osteoporosis. In this case, an anti-osteoporosis therapy becomes necessary. Considering severe adverse effects of systemic anti-osteoporosis drugs and limited local bone regeneration, the combination of scaffold implantation and local drug delivery can promote osteoporotic bone defect healing. Importantly, to incorporate bone regeneration inducers into scaffolds and steadily release with their biological activity is the key to success. Bisphosphonate, strontium, bone morphogenetic protein 2 and parathyroid hormone, traditional Chinese medicine and mesenchymal stem cells are the drugs commonly combined with tissue-engineered bone scaffolds. With the development of biotechnology, genetically modified stem cell-scaffold composites have gradually appealed to researchers.