Origin of critical nature and stability enhancement in collagen matrix based biomaterials: Comprehensive modification technologies

Collagen is the most abundant protein in animals and one of the most important extracellular matrices that chronically plays an important role in biomaterials. However, the major concern about native collagen is the lack of its thermal stability and weak resistance to proteolytic degradation. Currently, a series of modification technologies have been explored for critical nature and stability enhancement in collagen matrix-based biomaterials, and prosperously large-scale progress has been achieved. The establishment of covalent bonds among collagen noumenon has been verified assuringly to have pregnant influences on its physicochemical properties and biological properties, enlightening to discuss the disparate modification technologies on specific effects on the multihierarchical structures and pivotal performances of collagen. In this review, various existing modification methods were classified from a new perspective, scilicet whether to introduce exogenous substances, to reveal the basic scientific theories of collagen modification. Understanding the role of modification technologies in the enhancement of collagen performance is crucial for developing novel collagen-based biomaterials. Moreover, the different modification effects caused by the interaction sites between the modifier and collagen, and the structure-activity relationship between the structure of the modifier and the properties of collagen were reviewed.