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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

We have designed and synthesized several small libraries of chiral nitrogen-based ligands and tested their ability to provide stereoselectivity in selected transition metal-catalyzed reactions. Chapter 1 provides background for asymmetric catalysis and summarizes applications of trans-2,5-disubstituted pyrrolidine moieties as chiral auxiliaries and as building blocks for chiral ligands. Although these moieties have found many successful applications as chiral auxiliaries in different asymmetric reactions, application of chiral ligands derived from these moieties has been rare. Chapter 2 summarizes the synthesis of several small libraries of chiral ligands derived from trans-2,5-dimethylpyrrolidine and trans-2,5-diarylpyrrolidines. A modular synthetic strategy has been followed to ensure ease in constructing these libraries with diversity. Small libraries of pyridine-pyrrolidine ligands, bidentate N-O and N-S type ligands, bidentate and tridentate Schiff-base ligands, aminoalcohol ligands, tridentate N-N-O type ligands, C2-symmetric diamine ligands, and a cyclopalladated complex have been prepared. Chapter 3 summarizes the results of using these ligands in several transition metal-catalyzed asymmetric processes, including allylic alkylation, cyclopropanation and diethylzinc addition to benzaldehyde. The pyridine-pyrrolidine ligands are effective catalyst precursors for the palladium-catalyzed allylic alkylation and provided moderate to good stereoselectivities. The stereoselectivity of this reaction catalyzed by palladium complexes of the pyridine-pyrrolidine ligands could be adjusted by changing the substituents on the 6-position of the pyridine ring as well as the chelation size of the complexes. Evidence from these experimental results, 1H NMR studies and MM3* calculations suggested that nucleophilic attack to the 1,3-diphenylallyl moiety in the transition state mainly occurred trans to the pyridine ring of the less stable conformation of the palladium complexes.