Abstract:Collagen is the most abundant protein in mammals, accounting for about one-third of human protein. As an important component of the connective tissue and extracellular matrix, collagen is essential for maintaining physiological functions and repairing injuries and has important applications in the fields of medicine, food, and beauty. The main methods for producing collagen are natural extraction, chemical synthesis, and biosynthesis. Natural extraction from animal connective tissue has ethical issues, unstable quality, and infectious disease risks. Chemical synthesis is costly and it is not easy to synthesize complex collagen structures. Biosynthesis enables the production of recombinant collagen for different purposes by genetic engineering in a more controllable, safer, and more precise manner. However, due to the complex structure of collagen, its biosynthesis depends on specific molecular chaperones and modifying enzymes, and thus the production of recombinant collagen is challenging. In addition, different types of collagen need to form particular tissue structures, such as fibril, reticular, or transmembrane structures, which further increases the difficulty of production. This article clarifies the multifunctionality of recombinant human collagen, reviews the latest progress and challenges in its biosynthesis, and looks forward to future development directions. This review aims to help researchers, engineers, and industry practitioners understand the research trends of recombinant collagen and promote its further development and commercialization in different application fields.