Recent advances of collagen-based biomaterials: Multi-hierarchical structure, modification and biomedical applications.

Collagen is the most abundant structural protein of connective tissues including skin, tendon, bone and cartilage in mammals. The complicated biosynthesis of nature collagen in vivo, involving numerous intracellular and extracellular steps, causes it to have a multi-hierarchical fibrous architecture. The bioactivity of collagen is mostly depended on its tertiary structure or above. In the past decades, collagen biomaterials have received many attentions in biological applications due to its excellent properties, such as low immunogenicity, biodegradable, biocompatibility, hydrophilicity, easy processing, etc. However, collagen is also suffering from the poor physical and chemical properties (mechanical strength, thermostability, resistance to enzyme and so on). Therefore, the modification of collagen in preparation process is necessary. This review will shed light on the crosslinking methods and the recent advances of collagen-based materials in biomedical applications including skin substitute, bone repair, tendon repair, cartilage repair, neural repair and delivery system.