Heparin is the highest negatively charged biomolecule, which is a
polysaccharide belonging to the
glycosaminoglycan family, and its role as a regulator of various
proteins, cells and tissues in the human body makes it an indispensable macromolecule.
Heparin-based
hydrogels are widely investigated in various applications including implantation, tissue engineering, biosensors, and drug-controlled release due to the 3D-constructs of
hydrogels. However,
heparin has supply and safety problems because it is usually derived from animal sources, and has the clinical limitations of
bleeding and
thrombocytopenia. Therefore, analogous
heparin-mimicking
polymers and
hydrogels derived from non-animal and/or totally synthetic sources have been widely studied in recent years. In this review, the progress and potential biomedical applications of
heparin-based and
heparin-inspired
hydrogels are highlighted. We classify the forms of these
hydrogels by their size including macro-
hydrogels,
injectable hydrogels, and nano-
hydrogels. Then, we summarize the various fabrication strategies for these
hydrogels including chemical covalent bonding, physical conjugation, and the combination of chemical and physical interactions. Covalent bonding includes
free radical polymerization of vinyl-containing components,
amide bond formation reaction, Michael-type addition reaction, click-chemistry,
divinyl sulfone crosslinking, and mussel-inspired coating.
Hydrogels physically conjugated via host-guest interaction, electrostatic interaction, hydrogen bonding, and hydrophobic interaction are also discussed. Finally, we conclude with the challenges and future directions for the fabrication and the industrialization of
heparin-based and
heparin-inspired
hydrogels. We believe that this review will attract more attention toward the design of
heparin-based and
heparin-inspired
hydrogels, leading to future advancements in this emerging research field.