Click Chemistry-Based Injectable Hydrogels and Bioprinting Inks for Tissue Engineering Applications

Abstract

BACKGROUND: The tissue engineering and regenerative medicine approach require biomaterials which are biocompatible, easily reproducible in less time, biodegradable and should be able to generate complex three-dimensional (3D) structures to mimic the native tissue structures. Click chemistry offers the much-needed multifunctional hydrogel materials which are interesting biomaterials for the tissue engineering and bioprinting inks applications owing to their excellent ability to form hydrogels with printability instantly and to retain the live cells in their 3D network without losing the mechanical integrity even under swollen state. METHODS: In this review, we present the recent developments of in situ hydrogel in the field of click chemistry reported for the tissue engineering and 3D bioinks applications, by mainly covering the diverse types of click chemistry methods such as Diels-Alder reaction, strain-promoted azide-alkyne cycloaddition reactions, thiol-ene reactions, oxime reactions and other interrelated reactions, excluding enzyme-based reactions. RESULTS: The click chemistry-based hydrogels are formed spontaneously on mixing of reactive compounds and can encapsulate live cells with high viability for a long time. The recent works reported by combining the advantages of click chemistry and 3D bioprinting technology have shown to produce 3D tissue constructs with high resolution using biocompatible hydrogels as bioinks and in situ injectable forms. CONCLUSION: Interestingly, the emergence of click chemistry reactions in bioink synthesis for 3D bioprinting have shown the massive potential of these reaction methods in creating 3D tissue constructs. However, the limitations and challenges involved in the click chemistry reactions should be analyzed and bettered to be applied to tissue engineering and 3D bioinks. The future scope of these materials is promising, including their applications in in situ 3D bioprinting for tissue or organ regeneration.

Biological responses to physicochemical properties of biomaterial surface

“…374 Over the past two decades, copper-based ''click'' chemistry reactions have been a common strategy for synthesizing hydrogels. 375 In addition, bioorthogonal ''click'' chemistry is used to describe the way of generating products by joining small biomolecules such as proteins that occur in the presence of macromolecules such as proteins or cells. 375 Bio-orthogonal ''click'' chemistry is recognized as a promising molecular labeling approach, which does not affect normal biochemical processes.…”

“…375 In addition, bioorthogonal ''click'' chemistry is used to describe the way of generating products by joining small biomolecules such as proteins that occur in the presence of macromolecules such as proteins or cells. 375 Bio-orthogonal ''click'' chemistry is recognized as a promising molecular labeling approach, which does not affect normal biochemical processes. 376 Using these approaches, researchers can synthesize novel polymers and multifunctional hydrogels for biomedical applications.…”

An injectable, click-crosslinked, cytomodulin-modified hyaluronic acid hydrogel for cartilage tissue engineering

“…It was recently shown that the biorthogonal Diels-Alder click reaction between tetrazine (Tet) and transcyclooctene (TCO) can proceed rapidly under physiological conditions even in the absence of an external catalyst [28][29][30][31][32] . To our knowledge, there are very few published studies on the use of injectable click-cross-linked HA hydrogels in cartilage tissue engineering of hPLSCs.…”

Increasing the hydrophilicity of star‐shaped amphiphilic co‐networks by using of PEG and dendritic s‐PCL cross‐linkers

“…Amphiphilic hydrogels, as a new class of modern materials, have received significant attention recently . The simultaneous presence of incompatible hydrophilic and hydrophobic parts has endowed unique and interesting properties to these materials.…”

“…Amphiphilic hydrogels, as a new class of modern materials, have received significant attention recently. [1][2][3][4][5] The simultaneous presence of incompatible hydrophilic and hydrophobic parts has endowed unique and interesting properties to these materials. For example, due to the presence of the hydrophobic units, amphiphilic hydrogels have improved mechanical properties compared with homopolymer hydrophilic hydrogels.…”