Construction of tissue-customized hydrogels from cross-linkable materials for effective tissue regeneration

Hydrogels are prevalent scaffolds for tissue regeneration because of their hierarchical architectures along with outstanding biocompatibility and unique rheological and mechanical properties. For decades, researchers have found that many materials (natural, synthetic, or hybrid) can form hydrogels using different cross-linking strategies. Traditional strategies for fabricating hydrogels include physical, chemical, and enzymatical cross-linking methods. However, due to the diverse characteristics of different tissues/organs to be regenerated, tissue-customized hydrogels need to be developed through precisely controlled processes, making the manufacture of hydrogels reliant on novel cross-linking strategies. Thus, hybrid cross-linkable materials are proposed to tackle this challenge through hybrid cross-linking strategies. Here, different cross-linkable materials and their associated cross-linking strategies are summarized. From the perspective of the major characteristics of the target tissues/organs, we critically analyze how different cross-linking strategies are tailored to fit the regeneration of such tissues and organs. To further advance this field, more appropriate cross-linkable materials and cross-linking strategies should be investigated. In addition, some innovative technologies, such as 3D bioprinting, the internet of medical things (IoMT), and artificial intelligence (AI), are also proposed to improve the development of hydrogels for more efficient tissue regeneration.