Genetic Engineering Revolutionized Scaffold‐Based Bone Regeneration

Abstract Genetic modification ought to be regarded as a complementary technology that effectively enhances the efficacy of bone rehealing and substitution. Recently, molecular bone regeneration paths have been uncovered and a rapid advancement in gene therapy has led to heightened interest in bone regeneration and genetic engineering. Biomaterial scaffold‐mediated gene therapy offers a template for tissue development and cell infiltration. Gene‐activated platforms offer an efficient approach for precisely delivering genes to promote bone tissue regeneration in a safe and effective manner. Moreover, these pathways have the ability to temporarily regulate the excessive expression of therapeutic genes, resulting in the localized synthesis of regulatory factors at levels that are biologically significant. Therefore, the application of various nucleic acid‐based scaffolds including long noncoding RNAs, short interfering RNAs, microRNAs, coding mRNAs, plasmids, viral vectors, aptamers, and gene editing tools are comprehensively discussed in bone repair and regeneration. The bibliography reveals that collagen, calcium/phosphate‐based composites, and chitosan are the common scaffolds. Recombinant viruses, plasmids, miRNAs, and siRNAs are the most prevalent engineering methods. Research findings suggest that the integration of nucleic elements in biomaterials will revolutionize bone regeneration. Tremendous innovations will bring such engineered scaffolds from benches to clinics, very soon.