Gene-Activated Scaffolds in Bone Regeneration: Advances in Gene Delivery and Osteogenic Engineering: A Literature Review Article Publisher



Faridghiasi F ; Esmailabad S G ; Moeinzadeh A ; Shamlou S ; Kiani J
Source: Regenerative Engineering and Translational Medicine Published:2026

Abstract

Abstract: Genome engineering has emerged as a promising tool in bone tissue engineering, offering new strategies to enhance scaffold design and functionality for bone regeneration. By integrating principles from molecular biology, materials science, and biomedical engineering, gene-modified scaffolds can mimic the bone extracellular matrix (ECM), improving cell adhesion, proliferation, and differentiation. The use of advanced tools such as CRISPR/Cas9 has enabled precise genetic modifications, enhancing scaffold biocompatibility and osteoinductive potential. Gene-activated scaffolds, capable of delivering therapeutic genes directly to bone defects, offer a cost-effective alternative to protein-based treatments and address limitations of traditional grafts. Additionally, technologies like 3D bioprinting have enabled the fabrication of anatomically accurate scaffolds with improved integration and mechanical performance. The convergence of genome editing and tissue engineering presents a transformative approach for treating genetic bone disorders, such as osteogenesis imperfecta (OI). However, clinical application requires careful consideration of safety, efficacy, and ethical concerns. Continued development of gene-enhanced scaffolds, alongside robust regulatory frameworks, will be essential for advancing bone regeneration therapies. Lay Summary: Bone regeneration remains a major challenge in patients with severe bone injuries or genetic bone disorders. Recentadvances in genome engineering and tissue engineering have created new opportunities for improving bone repair. Thisreview discusses how modern gene-editing technologies, such as CRISPR/Cas9, can be combined with advancedbiomaterial scaffolds to enhance bone healing. These engineered scaffolds can deliver therapeutic genes directly todamaged bone tissue, stimulate new bone formation, and improve the integration of implants with surrounding tissues.The article also reviews different scaffold materials, gene delivery systems, and emerging technologies such as 3Dbioprinting. In addition, the review highlights current challenges, including safety, ethical considerations, and regulatoryissues that must be addressed before these technologies can be widely used in clinical practice. Overall, genome-engineered bone scaffolds represent a promising future strategy for treating bone defects and genetic skeletal disorders. © The Author(s), under exclusive licence to The Regenerative Engineering Society 2026.