Bio-Inspired Copper Coordination Bonds Enable Tunable, Viscoelastic, and Cytocompatible Polyhydroxyalkanoates

Biomaterials for repair and regeneration of soft tissues are ideally viscoelastic and processable. One way to obtain such materials is through dynamic cross-linking. Inspired by the high abundance of histidine residues in copper metalloproteins, we synthesized PHA copolymers containing imidazole side chains. The addition of a small amount of copper-(II) ions results in the formation of dynamically cross-linked materials whose properties are controlled by varying the copolymer composition and counterion identity. These materials are cytocompatible with human umbilical vein endothelial cells and exhibit promising degradation timelines. This work will inform the future use of dynamically cross-linked polyhydroxyalkanoates in soft tissue applications and provide a platform for accessing the wide range of material properties necessary for many organs in the human body.