Abstract
Critical-sized bone defects represent an urgent clinical problem, necessitating innovative treatment approaches. Gene-activated grafts for bone tissue engineering have emerged as a promising solution. However, traditional gene delivery methods are constrained by limited osteogenic efficacy and safety concerns. Recently, organic and inorganic nanoparticle (NP)vectors have attracted significant attention in bone tissue engineering for their safe, stable, and controllable gene delivery. Targeted gene delivery guided by insights into bone healing mechanisms, coupled with the multifunctional design of NPs, is crucial for enhancing therapeutic outcomes. Here, the theoretical foundations underlying NP-mediated gene therapy for enhancing bone healing across different histological stages are elucidated. Furthermore, the distinct attributes of functionalized NP vectors are discussed, and cutting-edge strategies aimed at optimizing gene delivery efficiency throughout the therapeutic process are highlighted. Additionally, the review addresses the unresolved challenges and prospects of this technology. This review may contribute to the continued development and clinical application of NP-mediated gene delivery for treating critical-sized bone defects.
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