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.