Abstract
BACKGROUND AND PURPOSE: Micro-/nano-tubes (TNTs) and micro-/nano-nets (TNNs) are the common and sensible choice in the first step of combined modifications of titanium surface for further functionalization in the purpose of extended indications and therapeutic effect. It is important to recognize the respective biologic reactions of these two substrates for guiding a biologically based first-step selection. MATERIALS AND METHODS: TNTs were produced by anodic oxidation and TNNs were formed by alkali-heat treatment. The original selective laser melting (SLM) titanium surface was set as control. Surface characterization was evaluated by scanning electron microscopy, surface roughness, and water contact angle measurements. Osteoclastogenesis and osteogenesis were measured. MC3T3-E1 cells and RAW 264.7 cells were used for in vitro assay in terms of adhesion, proliferation, and differentiation. In vivo assessments were taken on Beagle dogs with micro-CT and histological analysis. RESULTS: TNN and TNT groups performed decreased roughness and increased hydrophilicity compared with SLM group. For biological detections, the highest ALP activity and osteogenesis-related genes expression were observed in TNT group followed by TNN group (P <0.05). Interestingly, when it comes to the osteoclastogenesis, TNNs displayed lowest TRAP activity and osteoclastogenesis-related genes expression and TNTs were lower than SLM but higher than TNNs (P <0.05). BV/TV around implants was highest in TNT group after 4 weeks (P <0.05). HE, ALP and TRAP staining showed that osteogenic and osteoclastic activity around TNTs were both higher than TNNs (P <0.05). CONCLUSION: TNNs and TNTs have dual advantages in promotion of osteogenesis and inhibition of osteoclastogenesis. Furthermore, TNNs showed better capability in inhibiting osteoclast activity while TNTs facilitated stronger osteogenesis. Our results implied that TNT substrates would take advantage in early application after implantation, while diseases with inappropriate osteoclast activity would prefer TNN substrates, which will guide a biologically based first-step selection on combined modification for different clinical purposes.