去铁胺在骨组织再生中的应用进展

Application of deferoxamine in bone tissue regeneration

背景:除了铁络合作用外,去铁胺还被认为是一种有效的低氧模拟剂及缺氧诱导因子1α稳定剂,近年的基础及临床研究中去铁胺也表现出良好的骨再生效应。去铁胺溶液或负载去铁胺的生物支架被局部应用于骨组织工程中,其对骨再生的促进涉及多种功能特性及分子机制,但尚未完全明确,且其在骨再生中的研究进展缺乏有效总结。目的:对去铁胺应用于骨再生的功能特性、优缺点及其在基础研究及临床实践中的进展进行综述,以期为后续相关研究提供参考及策略。方法:以“deferoxamine OR desferrioxamine OR desferal OR DFO”“bone tissue engineering OR bone regeneration OR bone remodeling OR bone repair OR bone healing OR osteogenesis”“angiogenesis OR vascularized bone regeneration OR angiogenic-osteogenic coupling”为英文检索词检索PubMed数据库,以“去铁胺”“骨组织工程,骨再生,骨重建,骨修复,骨愈合”“成血管,血管化成骨,成骨-成血管偶联”为中文检索词检索万方和中国知网数据库,最终纳入88篇文献进行综述。结果与结论:①去铁胺能招募干细胞并调节干细胞功能,激活相关信号通路提高细胞的低氧适应能力,发挥抗炎抗氧化特性改善局部炎性环境,并通过偶联成骨-成血管及抑制骨吸收来促进骨再生。②相较于传统骨组织工程中加载的生长因子或多肽,去铁胺作为小分子药物具有独特的优势,同时也存在毒性反应及应用局限,因此优化载药形式及剂量是必要的。③去铁胺独特的成血管-成骨偶联能力,在不同类型的骨损伤如骨折、骨坏死、牵张成骨、骨移植、口腔相关成骨及骨缺损中,因对骨愈合过程中血管生成的加强而更能适应和解决复杂多变的临床情况及个体差异下造成的骨修复困难;但同时也需要对去铁胺的应用方式及安全剂量加以对比和优化,利于其应用范围的扩大及临床价值的提升。

BACKGROUND:Aside from iron chelating,deferoxamine is also considered as an effective hypoxia mimetic agent and hypoxia inducible factor-1αstabilizer.Deferoxamine has played a favorable effect on bone regeneration in both basic and clinical research recently.Deferoxamine solutions or deferoxamine loaded bio-scaffolds have been locally applied in bone tissue engineering,and their promotion of bone repair involves various functional properties and molecular mechanisms which have not been entirely clarified.Moreover,their advances in research of bone regeneration lack comprehensive summary as well.OBJECTIVE:To review the functional properties,relative merits and advances in basic research and clinical practice of deferoxamine applied in bone regeneration,attempting to provide references and strategies for further studies.