Early establishment of soft-tissue adhesion and seal at the transmucosal and transcutaneous surface of implants is crucial to prevent infection and ensure the long-term stability and function of implants. Herein, we tested the hypothesis that treatment of titanium with ultraviolet (UV) light would enhance its interaction with epithelial cells. X-ray spectroscopy showed that UV treatment significantly reduced the atomic percentage of surface carbon on titanium from 46.1% to 28.6%. Peak fitting analysis revealed that, among the known adventitious carbon contaminants, C-C and C=O groups were significantly reduced after UV treatment, while other groups were increased or unchanged in percentage. UV-treated titanium attracted higher numbers of human epithelial cells than untreated titanium and allowed more rapid cell spread. Hemi-desmosome-related molecules, integrin β4 and laminin-5, were upregulated at the gene and protein levels in the cells on UV-treated surfaces. The result of the detachment test revealed twice as many cells remaining adherent on UV-treated than untreated titanium. The enhanced cellular affinity of UV-treated titanium was equivalent to laminin-5 coating of titanium. These data indicated that UV treatment of titanium enhanced the attachment, adhesion, and retention of human epithelial cells associated with disproportional removal of adventitious carbon contamination, providing a new strategy to improve soft-tissue integration with implant devices.

Effects of UV-photofunctionalization on bone-to-titanium integration under challenging systemic conditions remain unclear. We examined the behavior and response of osteoblasts from sham-operated and ovariectomized (OVX) rats on titanium surfaces with or without UV light pre-treatment and the strength of bone-implant integration. Osteoblasts from OVX rats showed significantly lower alkaline phosphatase, osteogenic gene expression, and mineralization activities than those from sham rats. Bone density variables in the spine were consistently lower in OVX rats. UV-treated titanium was superhydrophilic and the contact angle of ddH2O was ≤5°. Titanium without UV treatment was hydrophobic with a contact angle of ≥80°. Initial attachment to titanium, proliferation, alkaline phosphatase activity, and gene expression were significantly increased on UV-treated titanium compared to that on control titanium in osteoblasts from sham and OVX rats. Osteoblastic functions compromised by OVX were elevated to levels equivalent to or higher than those of sham-operated osteoblasts following culture on UV-treated titanium. The strength of in vivo bone-implant integration for UV-treated titanium was 80% higher than that of control titanium in OVX rats and even higher than that of control implants in sham-operated rats. Thus, UV-photofunctionalization effectively enhanced bone-implant integration in OVX rats to overcome post-menopausal osteoporosis-like conditions.

PURPOSE: Zirconia is a potential alternative to titanium for dental and orthopedic implants. Here we report the biological and bone integration capabilities of a new zirconia surface with distinct morphology at the meso-, micro-, and nano-scales. METHODS: Machine-smooth and roughened zirconia disks were prepared from yttria-stabilized tetragonal zirconia polycrystal (Y-TZP), with rough zirconia created by solid-state laser sculpting. Morphology of the surfaces was analyzed by three-dimensional imaging and profiling. Rat femur-derived bone marrow cells were cultured on zirconia disks. Zirconia implants were placed in rat femurs and the strength of osseointegration was evaluated by biomechanical push-in test. RESULTS: The rough zirconia surface was characterized by meso-scale (50 µm wide, 6-8 µm deep) grooves, micro-scale (1-10 µm wide, 0.1-3 µm deep) valleys, and nano-scale (10-400 nm wide, 10-300 nm high) nodules, whereas the machined surface was flat and uniform. The average roughness (Ra) of rough zirconia was five times greater than that of machined zirconia. The expression of bone-related genes such as collagen I, osteopontin, osteocalcin, and BMP-2 was 7-25 times upregulated in osteoblasts on rough zirconia at the early stage of culture. The number of attached cells and rate of proliferation were similar between machined and rough zirconia. The strength of osseointegration for rough zirconia was twice that of machined zirconia at weeks two and four of healing, with evidence of mineralized tissue persisting around rough zirconia implants as visualized by electron microscopy and elemental analysis. CONCLUSION: This unique meso-/micro-/nano-scale rough zirconia showed a remarkable increase in osseointegration compared to machine-smooth zirconia associated with accelerated differentiation of osteoblasts. Cell attachment and proliferation were not compromised on rough zirconia unlike on rough titanium. This is the first report introducing a rough zirconia surface with distinct hierarchical morphology and providing an effective strategy to improve and develop zirconia implants.