Novel pH-Responsive CaO2@ZIF-67-HA-ADH Coating That Efficiently Enhances the Antimicrobial, Osteogenic, and Angiogenic Properties of Titanium Implants

Titanium-based implants often lead to premature implant failure due to the lack of antimicrobial, osteogenic, and angiogenic properties. To this end, a new strategy was developed to fabricate CaO2@ZIF-67-HA-ADH coating on titanium surfaces by combining calcium peroxide (CaO2) nanoparticles, zeolite imidazolate framework-67 (ZIF-67), and the chemical coupling hyaluronic acid-adipic acid dihydrazide (HA-ADH). We characterized CaO2@ZIF-67-HA-ADH with scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma-atomic emission spectrometry (ICP-AES). The results demonstrated that CaO2@ZIF-67-HA-ADH was pH-sensitive and decomposed rapidly under acidic conditions, and it released inclusions slowly under neutral conditions. Antibacterial experiments showed that the CaO2@ZIF-67-HA-ADH coating had excellent antibacterial properties and effectively killed methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO-1). Cell experiments revealed that the CaO2@ZIF-67-HA-ADH coating promoted pro-osteoblast adhesion, proliferation, and differentiation and also promoted the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs), exhibiting excellent osteogenic and angiogenic properties. In in vivo animal implantation experiments, the CaO2@ZIF-67-HA-ADH coating exhibited strong antimicrobial activity early after implantation and excellent osseointegration later after implantation. In conclusion, the pH-responsive CaO2@ZIF-67-HA-ADH coating conferred excellent antibacterial, osteogenic, and angiogenic properties to titanium implants, which effectively enhanced osseointegration of the implants and prevented bacterial infection; the coating shows promise for use in the treatment of bone defects.