Biomaterial-Based Gene Delivery: Advanced Tools for Enhanced Cartilage Regeneration

Hongfeng Chen,1 Zhen Li,1 Xiaoqi Li,1 Jiongjiong Lu,1 Beibei Chen,1 Qiongchao Wang,1 Guangliang Wu2 1Department of Foot and Ankle Surgery, The Second Affiliated Hospital of Luohe Medical College, Luohe, Henan, 462300, People’s Republic of China; 2Department of Orthopaedics, The Second Affiliated Hospital of Luohe Medical College, Luohe, Henan, 462300, People’s Republic of ChinaCorrespondence: Guangliang Wu, Department of Orthopaedics, The Second Affiliated Hospital of Luohe Medical College, Western Haihe Road, Luohe, Henan, 462300, People’s Republic of China, Email wuguangliang6@sina.comAbstract: Gene therapy has emerged as a promising and innovative approach in cartilage regeneration. Integrating biomaterials into gene therapy offers a unique opportunity to enhance gene delivery efficiency, optimize gene expression dynamics, modulate immune responses, and promote tissue regeneration. Despite the rapid progress in biomaterial-based gene delivery, there remains a deficiency of comprehensive discussions on recent advances and their specific application in cartilage regeneration. Therefore, this review aims to provide a thorough overview of various categories of biomaterials employed in gene delivery, including both viral and non-viral vectors, with discussing their distinct advantages and limitations. Furthermore, the diverse strategies employed in gene therapy are discussed and summarized, such as the utilization of growth factors, anti-inflammatory cytokines, and chondrogenic genes. Additionally, we highlights the significant challenges that hinder biomaterial-based gene delivery in cartilage regeneration, including immune response modulation, gene delivery efficiency, and the sustainability of long-term gene expression. By elucidating the functional properties of biomaterials-based gene therapy and their pivotal roles in cartilage regeneration, this review aims to enhance further advances in the design of sophisticated gene delivery systems for improved carti