Novel pH-Responsive CaO@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 CaO@ZIF-67-HA-ADH coating on titanium surfaces by combining calcium peroxide (CaO) nanoparticles, zeolite imidazolate framework-67 (ZIF-67), and the chemical coupling hyaluronic acid-adipic acid dihydrazide (HA-ADH). We characterized CaO@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 CaO@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 CaO@ZIF-67-HA-ADH coating had excellent antibacterial properties and effectively killed methicillin-resistant (MRSA) and (PAO-1). Cell experiments revealed that the CaO@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 CaO@ZIF-67-HA-ADH coating exhibited strong antimicrobial activity early after implantation and excellent osseointegration later after implantation. In conclusion, the pH-responsive CaO@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.