Fabrication of copper ions-substituted hydroxyapatite/polydopamine nanocomposites with high antibacterial and angiogenesis effects for promoting infected wound healing

Abstract

Infected wound healing remains a critical threat, which frequently delays the healing process and even leads to severe life-threatening complications. Herein, we reported an effective anti-infection approach, which was based on copper ions-releasing hydroxyapatite/polydopamine (HA-Cu/PDA) nanocomposites with photothermal effect. The HA-Cu/PDA nanocomposites was fabricated through a co-precipitation reaction between polydopamine (PDA)-coated hydroxyapatite nanoparticles (HA)-loaded Cu2+ (HA-Cu). Through a synergistic effect of released Cu2+ and photothermal efficiency of PDA coating, and the HA-Cu/PDA nanocomposites exhibited extraordinary antibacterial capacities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The nanocomposites presented good biocompatibility for mouse embryonic fibroblast (NIH-3T3) cells and promoted NIH3T3 cells to migrate toward wound sites. Additionally, this nanocomposite could stimulate the tissue remodeling-related gene expression to induce the blood vessels formation, granulation tissues and collagen deposition, and eventually enhance wound healing. In vivo study further verified that HA-Cu/PDA nanocomposites with NIR irradiation could significantly improve bacterial infected wound healing through the prominent antibacterial property, reduced inflammatory response, the formation of granulation tissue, collagen deposition, and angiogenesis ability. Thus, this study develops a versatile strategy for a broad range of wound healing and skin reconstruction caused by bacterial infection.