Effect of Polymer Topology and Residue Chirality on Biodegradability of Polypeptide Hydrogels

Polypeptide-based injectable hydrogels have attracted the attention of biomedical researchers due to their unique biocompatibility and biodegradability, tunable residue chirality, and secondary conformation of polypeptide chains. In the present study, four types of poly(ethylene glycol)-block-poly(glutamic acid)s with different topological structures and residue chirality of polypeptide segments were developed, which were grafted with tyramine side groups for further cross-linking. The results demonstrated that the covalent conjugation between the tyramine groups in the presence of horseradish peroxidase and hydrogen peroxide could form porous hydrogels rapidly. Additionally, the gelation time and mechanical strength of the hydrogels were measured. All the polymer precursors and hydrogels exhibited good cytocompatibility in vitro. Further assessment of the enzymatic degradability of the hydrogels and copolymers in vitro revealed that the degradation rate was influenced by the adjustment of polymer topology or residue chirality of polypeptide copolymers. Subsequently, the effect of copolymer topology and polypeptide chirality on in vivo biodegradability and biocompatibility was assessed. This study will provide insights into the relationship between copolymer structures and hydrogel properties and benefit future polypeptide-based hydrogel studies in biomedical applications.