Recombinant collagen in regenerative medicine: Expression strategies, structural design, and translational applications

Recombinant collagen represents a new generation of biomaterials that integrate molecular precision, functional tunability, and scalable biomanufacturing. While animal-derived collagens remain clinically established, their inherent biological variability, limited controllability, and potential pathogen risks have spurred the development of recombinant systems capable of producing collagen with defined sequences and consistent quality. Advances in synthetic biology have enabled expression across diverse hosts-including <i>E. coli</i>, <i>yeast</i>, plants, mammalian cells, and transgenic organisms-each offering distinct advantages in yield, post-translational modification, and triple-helix assembly. Emerging molecular architectures, encompassing triple-helical recombinant collagens, non-helical gelatin-like proteins, and multifunctional fusion constructs, collectively expand the structural repertoire and functional landscape of recombinant collagen-based biomaterials. These engineered materials show strong promise in bone and cartilage regeneration, skin reconstruction, and corneal repair. Nonetheless, challenges remain in achieving complete hydroxylation, cost-effective large-scale manufacturing, and harmonized regulatory standards. The integration of AI-assisted sequence design, programmable molecular engineering, and GMP-compliant production is expected to accelerate clinical translation. By bridging molecular innovation with clinical application, recombinant collagen is poised to redefine the landscape of regenerative medicine and usher in a new era of precision-engineered biomaterials.