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

作者：Hu, Guansong; Chen, Junjian; Fan, Yan; Zhou, Haiyan; Guo, Kunzhong; Fang, Zhou; Xie, Liangxu^*; Wang, Lin^*; Wang, Yingjun^*

来源：Chemical Engineering Journal, 2022, 427: 130918.

DOI：10.1016/j.cej.2021.130918

• Click chemistry
• Nanocluster
• Peptide
• Implant

As an effective strategy to develop novel implants with a biomolecule, the efficiency of a copper-catalysed azidealkyne 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 allatom 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 YGFGGengineered 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.

• 单位
  江苏大学