In Situ 3D Bioprinting: Impact of Cross‐Linking on the Adhesive Properties of Hydrogels

ABSTRACT In situ 3D bioprinting is a rapidly evolving technology that has emerged as a transformative approach in tissue engineering. It involves the direct deposition of cell‐containing biomaterials into patients, facilitating on‐site tissue regeneration. Polymers that adhere to the surrounding tissue and mimic the extracellular matrix are key to success. To achieve high adhesive properties, bioadhesive hydrogels or bio‐glues are utilized. Bioadhesives used for in situ 3D bioprinting include natural and synthetic polymers, whose adhesive properties can be further improved by the introduction of functional groups. Cross‐linking ensures not only rapid gelation after the printing process but also high adhesive properties and mechanical strength of the hydrogel. The timing and degree of this cross‐linking thereby have a substantial impact on the performance of these hydrogels. This review aims to provide a comprehensive overview of the impact of cross‐linking on the bioadhesive properties of hydrogels used for 3D bioprinting. Triggers for cross‐linking and the relationship between bioadhesion and cross‐linking are highlighted. The mechanism of bioadhesion and polymer interpenetration into the target tissue, as well as the impact of cross‐linking on these mechanisms, are discussed, and an outlook on future trends, such as the use of primers to increase the number of binding sites on target tissues, is presented.