Biopolymers
are natural polymers sourced from plants and animals,
which include a variety of polysaccharides and polypeptides. The inclusion
of biopolymers into biomedical hydrogels is of great interest because
of their inherent biochemical and biophysical properties, such as
cellular adhesion, degradation, and viscoelasticity. The objective
of this Review is to provide a detailed overview of the design and
development of biopolymer hydrogels for biomedical applications, with
an emphasis on biopolymer chemical modifications and cross-linking
methods. First, the fundamentals of biopolymers and chemical conjugation
methods to introduce cross-linking groups are described. Cross-linking
methods to form biopolymer networks are then discussed in detail,
including (i) covalent cross-linking (e.g., free radical chain polymerization,
click cross-linking, cross-linking due to oxidation of phenolic groups),
(ii) dynamic covalent cross-linking (e.g., Schiff base formation,
disulfide formation, reversible Diels–Alder reactions), and
(iii) physical cross-linking (e.g., guest–host interactions,
hydrogen bonding, metal–ligand coordination, grafted biopolymers).
Finally, recent advances in the use of chemically modified biopolymer
hydrogels for the biofabrication of tissue scaffolds, therapeutic
delivery, tissue adhesives and sealants, as well as the formation
of interpenetrating network biopolymer hydrogels, are highlighted.