中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (22): 4771-4783.doi: 10.12307/2025.446

• 生物材料综述 biomaterial review • 上一篇    下一篇

纳米粒子在骨组织工程化基因修饰治疗中的应用

李光照,裴锡波,王  剑   

  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
  • 收稿日期:2024-05-06 接受日期:2024-06-13 出版日期:2025-08-08 发布日期:2024-12-06
  • 通讯作者: 王剑,博士,教授,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
  • 作者简介:李光照,女,1999年生,山西省人,汉族,四川大学华西口腔医(学)院在读硕士。
  • 基金资助:
    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

Application of nanoparticles in gene modification therapy for bone tissue engineering

Li Guangzhao, Pei Xibo, Wang Jian   

  1. 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
  • Received:2024-05-06 Accepted:2024-06-13 Online:2025-08-08 Published:2024-12-06
  • Contact: Wang Jian, MD, Professor, 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
  • About author:Li Guangzhao, Master candidate, 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
  • Supported by:
    National Natural Science Foundation of China, No. 82271034 (to WJ); National Natural Science Foundation of China, No. 82271016 (to PXB); Fund of Sichuan Provincial Department of Science and Technology, No. 2023ZYD0109 (to PXB)

摘要:


文题释义:

骨组织工程:由细胞、支架和生物活性物质组合构成的人工合成骨移植物,将其植入到体内骨缺损部位可以促进内源性骨再生。
纳米粒子载体:粒径为10-1 000 nm的微小粒子,可以由各种材料制备而成,微小的尺寸赋予其很多特殊的性质,非常适合作为载体运送核酸等生物大分子。


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PubMed、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,靶向性递送”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能设计来增强基因转染效率,包括增强缓释性和多基因递送序贯性等时间调控能力、增强对骨组织和成骨相关细胞的空间靶向能力、增强跨膜运输效率和细胞核靶向能力等全过程调控手段。④未来要进一步推动纳米粒子介导的骨组织工程基因治疗在临床上的应用,还需要克服诸多技术挑战,包括提高有机纳米基因载体的基因转染效率、降低无机纳米载体的生物安全性风险、优化新型纳米载体的生产工艺以及促进其它生理过程与成骨交互作用等,这些问题也是未来骨组织工程基因治疗的研究热点和潮流。

https://orcid.org/0000-0002-7804-3479 (李光照);https://orcid.org/0000-0002-5137-0330 (王剑)

中国组织工程研究杂志出版内容重点:生物材料;骨生物材料;口腔生物材料;纳米材料;缓释材料;材料相容性;组织工程

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

Abstract: 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 limitations. Therefore, in practical applications, selection of the appropriate type primarily depends on factors such as gene transfection efficiency, biocompatibility, and osteogenic properties. (3) To comprehensively improve the efficiency of gene delivery, the gene transfection efficiency of nanocarriers is mainly enhanced through various functional designs, including enhancing the temporal regulation ability such as slow release and multi-gene delivery sequence, enhancing the spatial targeting ability of bone tissue and osteoblast-related cells, enhancing the transmembrane transport efficiency and nuclear targeting ability. (4) Numerous challenges need to be overcome in order to further promote the clinical application of nanoparticle-mediated gene therapy for bone tissue engineering, including improving gene transfection efficiency of organic carriers, reducing biosafety risks of inorganic carriers, optimizing the production process of new types of nanocarriers, and promoting interactions between other physiological processes and osteogenesis. These are also research hotspots and trends of gene therapy for bone tissue engineering in the future.

Key words: bone defect repair, bone tissue engineering, gene delivery, nanoparticle, non-viral gene vector, sustained release technology, sequential release, targeted delivery

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