Application of nanoparticles in gene modification therapy for bone tissue engineering
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.
万方数据
维普
