Effects of the chirality of amino acid residues on the properties of peptide-based hydrogels

Hydrogels possess three-dimensional (3D) hydrophilic or amphiphilic networks composed of a large amount of water. Due to the similarity in physicochemical properties of biological tissues, hydrogels have been widely investigated for various biomedical applications including drug delivery, 3D cell culture, and tissue engineering. Based on the resources, hydrogels can be divided into naturally derived hydrogels and synthetic hydrogels. The former is mainly based on chitosan, hyaluronic acid, gelatin and alginate, while the latter is commonly composed of poly(methacrylic acid) derivatives, polyethers, polyesters, and polypeptides. Among them, synthetic peptide-based hydrogels have attracted widespread attention due to their excellent biocompatibility, biodegradability, and unique compositions and structures analogous to proteins. As the basic structural units of peptide-based hydrogels, amino acids can be divided into L-amino acids and D-amino acids according to their chirality, except for achiral glycine. The chirality of amino acid residues will affect the microstructure of the self-assembled constructs of peptides. For example, Schlaad synthesized polypeptides with different secondary structures and properties by homo- or copolymerization of gamma-benzyl glutamate and allylglycine with different chirality. The polypeptides could be made into microspheres by direct emulsification and they showed a spiral surface structure in a dry state. The experiment proved that the spiral structure of the microspheres could be controlled by the chirality of the alpha-helical polypeptides. The right-handed alpha-helical polypeptide which is rich in L-amino acids self-assembled into clockwise spiral microsphere, whereas its enantiomer produced counterclockwise spirals. For peptide-based hydrogels, the chirality of amino acid residues affects not only their properties, but also their applications. In this review, we focus on the recent progress in peptide-based hydrogels with different chirality. We summarize the influence of amino acid residues chirality on the secondary structure, degradation, immunological response and biomedical applications such as cell culture and tissue regeneration scaffold, antibacterial activity and anti-tumor effects of the hydrogels. In general, the introduction of D-amino acids into the hydrogels enhances its resistance to proteolysis and the host immune response. In addition, the residue chirality also has an impact on the biomedical applications including cell behavior, bone repair, hemostasis, antibacterial activity, and antitumor efficiency. In a word, chirality as one of the basic properties of amino acids may play an important role in affecting the properties and biomedical applications of peptide-based hydrogels. It is worth pointing out that the mechanism of chirality effect on hydrogel properties and applications is not completely clear, and the related theoretical research needs to be further deepened. In addition, most of the current studies on the chirality of amino acid residues are focused on self-assembled hydrogels of peptides with defined compositions and residue sequences. The researches on polypeptide hydrogels are relatively limited, which may attract more interest in future studies since these materials have received progressive attention for biomedical applications recently.