Synthesis Methods of In Situ Forming Injectable Hydrogels and Their Applications in Tissue Engineering: A Review

Tissue engineering is a triad involves three components of different types of cells, growth factor, small biomolecules and scaffold for the purpose of tissue restore, repair and regeneration. In tissue engineering, attachment, growth, proliferation and differentiation of cells require careful control of external factors such as the physical properties of the scaffold as extra cellular matrix (ECM), type and amount of biologically active molecules like small biomolecules, peptides and proteins. Therefore, the interaction of the synthetic and natural scaffolds with the cells must reflect the cellular microenvironment in the body. In this study, we describe a variety of in situ forming injectable hydrogels synthesis with the medical application and tissue regeneration that are crosslinked by chemical bonding or physical interactions. These types of hydrogels have attracted a lot of attention in tissue engineering applications because they can easily transfer the cells or delivered the biomolecules to the damaged tissue. Lack of severe toxicity, minimal injury and pain during surgery could be the other advantages of the injectable hydrogels. A wide variety of chemical methods have been used to crosslink the injectable hydrogels such as click chemistry, Michael addition, Schiff-base, enzymatic reaction and, etc. Some hydrogels can also be cross-linked using physical interactions such as ionic interactions, hydrogen bonding, supramolecular interaction, etc., without external factors in the physiological conditions of the body. In this study, in addition to various methods of synthesis, the practical aspects of hydrogels in regenerative medicine and their achievements in tissue engineering are discussed.