纳米粒子在骨组织工程化基因修饰治疗中的应用  

Application of nanoparticles in gene modification therapy for bone tissue engineering

作　　者：李光照 裴锡波 王剑[1] Li Guangzhao;Pei Xibo;Wang Jian(State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases,Department of Prosthodontics of West China Hospital of Stomatology,Sichuan University,Chengdu 610041,Sichuan Province,China)

机构地区：[1]口腔疾病防治全国重点实验室,国家口腔医学中心,国家口腔疾病临床医学研究中心,四川大学华西口腔医院修复科,四川省成都市610041

出　　处：《中国组织工程研究》2025年第22期4771-4783,共13页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(82271034),项目负责人:王剑;国家自然科学基金项目(82271016),项目负责人:裴锡波;四川省中央引导地方科技发展专项项目(2023ZYD0109),项目负责人:裴锡波。

摘　　要：背景:传统的骨组织工程技术治疗临界骨缺损存在成骨效率低、安全性差等问题。而以非病毒纳米粒子为基因载体构建的基因强化型骨组织工程移植物,具有更高的成骨效率和安全性,引起了国内外学者的广泛关注和研究。目的:对当前国内外有关纳米粒子在组织工程成骨基因治疗研究中取得的新技术、新方法以及面临的挑战等进行综述,旨在为纳米粒子介导的骨组织工程基因治疗研究提供参考。方法:第一作者在Pub Med、Web of Science和中国知网数据库上进行文献检索,并以“Bone defect repair,Bone tissue engineering,Gene delivery,Nanoparticles,Non-viral gene vector,Sustained release technology,Sequential release,Targeted delivery”作为英文检索词,以“骨缺损修复,骨组织工程,基因递送,纳米粒子,非病毒基因载体,缓释技术,序贯释放,靶向递送”作为中文检索词,最终纳入84篇文献进行总结。结果与结论:(1)在骨缺损愈合的各个生理阶段进行针对性的基因递送可以显著增强骨修复效果。在早期炎症阶段,通过纳米粒子递送抗炎基因来调节炎症反应,可以为后续骨愈合奠定基础;在血管新生期,向局部递送促血管化基因有助于形成高度组织化、可灌注的血管系统,加快骨愈合速度;随着血管化的进行,骨骼的神经再支配也开始发生,此时递送促神经再生的功能性基因有利于促进神经化骨再生;在成骨阶段,通过构建纳米粒子-成骨基因复合物,可以直接提升支架及体内新骨形成的效率。(2)各种有机、无机纳米颗粒、金属有机框架和外泌体等非病毒纳米载体,在骨组织工程基因治疗中具有巨大的潜力,这些纳米基因载体各有其独特的优势和不足,因此在实际应用时,需要根据基因转染效率、生物安全性和成骨特性等因素选择最合适的类型。(3)为了全面提升递送基因的效果,目前主要通过对纳米载体进行各种功BACKGROUND:Traditional bone tissue engineering techniques for treating critical bone defects suffer from low osteogenic efficiency and poor safety.Gene-enhanced bone tissue engineering grafts constructed with non-viral nanoparticles have attracted widespread attention from scholars both domestically and internationally due to their higher osteogenic rates and safety,leading to extensive research in this field.OBJECTIVE:To review new technologies,methods,and challenges in the research of nanoparticles in gene therapy for bone tissue engineering,aiming to provide a reference for research on gene therapy mediated by nanoparticles in bone tissue engineering.METHODS:The first author searched PubMed,Web of Science,and CNKI.The Chinese and English search terms were“bone defect repair,bone tissue engineering,gene delivery,nanoparticles,non-viral gene vector,sustained release technology,sequential release,targeted delivery.”Finally,84 articles were included for summary.RESULTS AND CONCLUSION:(1)Targeted gene delivery at various physiological stages of bone defect healing can significantly enhance bone repair efficacy.In the early inflammatory stage,delivering anti-inflammatory genes via nanoparticles to regulate the inflammatory response lays the foundation for subsequent bone healing.During the angiogenesis phase,local delivery of vascularization target genes aids in forming a highly organized vascular system,significantly accelerating bone healing.As vascularization progresses,neural re-innervation of the bone begins;at this stage,delivering functional genes promoting nerve regeneration facilitates neuro-osteogenic regeneration.During the osteogenic phase,constructing nanoparticle-bone gene complexes directly enhances the efficiency of bone formation on scaffold and in vivo.(2)Non-viral nanocarriers such as various organic and inorganic nanoparticles,metal-organic frameworks,and exosomes show immense potential in gene therapy for bone tissue engineering.Each of these carriers has its unique advantages and limitation

关 键 词：骨缺损修复 骨组织工程 基因递送 纳米粒子 非病毒基因载体 缓释技术 序贯释放 靶向性递送 

分 类 号：R452[医药卫生—治疗学] R318.08[医药卫生—临床医学] R450