Precision synthesis strategies and emerging applications of bioorthogonal click chemistry in tissue engineering and regenerative medicine

Bioorthogonal click chemistry is a reaction that covalently connects 2 components via clickable groups at room or body temperature, without side reactions or by-products. It solves the common problems of traditional organic chemistry, such as harsh reaction conditions, slow reaction rate, and extremely low yield. Importantly, the specificity between clickable groups does not affect other biochemical reactions in the life system during the reaction. Therefore, it not only makes the organic synthesis reaction more simple, accurate, and efficient but also successfully introduces it into organisms, enabling people to intervene and study a series of biological processes in the life system. Due to its unique advantages in the construction of biomaterials and the transformation of cells, bioorthogonal click chemistry plays an increasingly important role in the field of tissue engineering and regenerative medicine and has made considerable progress. Herein, we present the latest progress of bioorthogonal click chemistry in the synthesis and functionalization of biomaterials and the interaction between biomaterials and cells. In addition, we also introduced examples of the application of these strategies in the repair of bone, skin, nerve, and other tissue or organ damage and discussed the future development direction of these strategies as cross-linking tools in the field of tissue engineering and regenerative medicine.