A promoted copper-catalysed Azide-alkyne cycloaddition (CuAAC) for broad spectrum peptide-engineered implants

Abstract As an effective strategy to develop novel implants with a biomolecule, the efficiency of a copper-catalysed azide-alkyne cycloaddition (CuAAC) urgently requires improvement. Herein, we constructed a facile CuAAC system with catalytic CuSO4/sodium borohydride (CuAAC-Bor). As Cu nanoclusters (CuNCs) formed in situ, they showed stronger efficiency in immobilizing 41 types of peptides on Ti implants than traditional CuAAC with CuSO4/sodium ascorbate. Then, we mechanically revealed the significance of peptide size on CuAAC efficiency by all-atom molecular dynamics simulation and machine learning, and found that larger peptides preferred to adhere to Ti and CuNCs to increase their reaction opportunity. With CuAAC-Bor, HHC36-engineered implants strongly inhibited 5 types of clinical bacteria in vitro and prevented infection in vivo, and RGD-, DGEA-, QK- or YGFGG-engineered implants had high biocompatibilities with HUVECs/hBMSCs in vitro. Moreover, we demonstrated that QK-engineered implants prepared with CuAAC-Bor promoted the osteogenic differentiation of hBMSCs via the PI3K/Akt signalling pathway and triggered angiogenesis and osteogenesis in vivo. Our study shows that this facile and highly efficient CuAAC-Bor system holds high promise for the preparation of novel biomaterial surfaces.