Recent trends in metal ion based hydrogel biomaterials for tissue engineering and other biomedical applications

Recently, the metal ion cross-linked hydrogels have gained enormous interest because of its excellent properties like self-healing, fast recovery, biocompatibility and high mechanical properties combined with multi-stimuli responsiveness. In this review article, we have summarized the recent trends in the development of metal ion cross-linked hydrogels for tissue engineering and biomedical applications. A number of metal ions and their contribution in the synthesis of various cross-linked hydrogels are discussed with respect to their crosslinking mechanisms, compositions, physio-chemical and biological properties. A special emphasis has been given to ferric (Fe 3+ ) ion cross-linked hydrogels and their different combinations owing to their numerous researches reported in the recent past with exceptional properties. The application of these metal ion based hydrogels in biomedical applications including tissue engineering, sensing, wound healing, drug delivery and as tissue adhesive and tissue sealants are reviewed with specific examples. Importantly, the application of these metal ion cross-linked hydrogels as inks in 3D printing is explained in a separate section. Finally, the possible toxic effects of the different metal ions and their effects have been scrutinized. Future directions and comprehensive applications of the hydrogels are highlighted.