金属离子掺杂羟基磷灰石骨修复材料的特性及应用

Characteristics and application of bone repair materials of metal ion doped hydroxyapatite

背景:目前用于骨修复的自体骨和异体骨存在来源有限、供骨区并发症、潜在的疾病传播风险、免疫排斥反应及价格昂贵等问题,临床应用受到限制,人工骨修复材料作为骨移植替代材料得到了广泛研究。目的:总结金属离子掺杂改性羟基磷灰石用于骨组织修复的研究现状。方法:检索2000年1月至2022年5月PubMed、Web of Science、中国知网及万方数据库收录的相关文献,中文检索词为“金属离子、羟基磷灰石、掺杂改性、骨修复”,英文检索词为“Metal ion,Hydroxyapatite,Doping modification,Bone repair”。最终纳入61篇文献进行综述分析。结果与结论:①离子掺杂羟基磷灰石具有良好的特性,锶可增强成骨细胞的骨生成过程,并抑制破骨细胞介导的骨吸收,锶掺杂羟基磷灰石在骨质疏松性骨缺损修复方面具有独特的优势。②铜、锌、银、镁、铁具有一定的抗菌活性,其中银、锌具有优异的抗菌性,掺杂改性羟基磷灰石对预防和治疗骨科感染具有重要意义。③铜可促进血管内皮细胞迁移,增加血管生成,掺铜羟基磷灰石可用于乏血管部位的骨组织修复。钡具有显影性,与羟基磷灰石等其他材料复合可制备显影骨修复材料。④锶-铁共掺杂羟基磷灰石可调节细胞免疫,促进血管和骨生成。镁、锌-锶掺杂的羟基磷灰石可诱导利于成骨的弱碱性环境,具有优异的成骨能力。⑤一定含量的镁掺杂的羟基磷灰石具有与皮质骨相匹配的抗压强度,有望用于负重部位的骨组织修复。低浓度的离子掺杂可提高羟基磷灰石的机械性能和成骨活性,并赋予其抗菌活性、促血管生成、免疫调节等能力。⑥当离子浓度过高时,则会产生毒性作用,目前关于各离子的最佳掺杂浓度尚无定论,未来需深入研究。⑦离子参与骨代谢的机制以及是否会影响其他细胞活动需关注探索;如何实现植入材料的缓慢降解、金属离子的缓慢释放,使其与骨修复过程相匹配,有待进一步研究。⑧优化羟基磷灰石的合成方法和离子掺杂技术,制备与天然骨机械性能匹配的材料是今后研究的一个方向。

BACKGROUND:Autologous and allogeneic bone currently used for bone repair has limited sources,complications in the donor area,potential risk of disease transmission,immune rejection,and high prices,which have limited clinical applications.Artificial bone repair materials have been widely studied as bone graft replacement materials.OBJECTIVE:To summarize the current status of research on metal ion-doped modified hydroxyapatite for bone tissue repair.METHODS:The articles collected in PubMed,Web of Science,CNKI and Wanfang databases were searched from January 2000 to May 2022.The Chinese and English search terms were“metal ion,hydroxyapatite,doping modification,bone repair”.Finally,61 articles were included for review.RESULTS AND CONCLUSION:(1)Ion doped hydroxyapatite has good characteristics.Strontium can enhance the osteogenesis of osteoblasts and inhibit osteoclast mediated bone resorption.Strontium doped hydroxyapatite has unique advantages in the repair of osteoporotic bone defects.(2)Copper,zinc,silver,magnesium and iron have certain antibacterial activity,among which silver and zinc have excellent antibacterial activity.Doping modified hydroxyapatite is of great significance for the prevention and treatment of orthopedic infections.(3)Copper can promote the migration of vascular endothelial cells and increase angiogenesis.Copper doped hydroxyapatite can be used to repair bone tissue lacking blood vessels.Barium has developing property,and it can be compounded with hydroxyapatite and other materials to prepare developing bone repair materials.(4)Strontium Iron Co doped hydroxyapatite can regulate cellular immunity and promote angiogenesis and bone formation.Magnesium,zinc strontium doped hydroxyapatite can induce a weak alkaline environment conducive to osteogenesis,and has excellent osteogenic ability.(5)A certain amount of magnesium doped hydroxyapatite has the compressive strength matching with cortical bone,and is expected to be used for bone tissue repair in weight-bearing sites.Low concentration ion doping can improve the mechanical properties and osteogenic activity of hydroxyapatite,and endow it with antibacterial activity,angiogenesis promotion,immune regulation,and so on.(6)When the ion concentration is too high,it will produce toxic effects.At present,there is no final conclusion about the optimal doping concentration of each ion,which needs to be further studied in the future.(7)The mechanism of ion involvement in bone metabolism and whether it will affect other cell activities need to be explored.How to realize the slow degradation of implant materials and the slow release of metal ions to match the process of bone repair needs to be further studied.(8)Optimizing the synthesis method and ion doping technology of hydroxyapatite to prepare materials that match the mechanical properties of natural bone is a research direction in the future.