The excessive accumulation of reactive oxygen species (ROS) under osteoporosis precipitates a microenvironment with high levels of oxidative stress (OS). This could significantly interfere with the bioactivity of conventional titanium implants, impeding their early osseointegration with bone. We have prepared a series of strontium (Sr)-doped titanium implants via micro-arc oxidation (MAO) to verify their efficacy and differences in osteoinduction capabilities under normal and osteoporotic (high OS levels) conditions. Apart from the chemical composition, all groups exhibited similar physicochemical properties (morphology, roughness, crystal structure, and wettability). Among the groups, the low Sr group (Sr25%) was more conducive to osteogenesis under normal conditions. In contrast, by increasing the catalase (CAT)/superoxide dismutase (SOD) activity and decreasing ROS levels, the high Sr-doped samples (Sr75% and Sr100%) were superior to Sr25% in inducing osteogenic differentiation of MC3T3-E1 cells and the M2 phenotype polarization of RAW264.7 cells, thus enhancing early osseointegration. Furthermore, the results of both in vitro cell co-culture and in vivo studies also showed that the high Sr-doped samples (especially Sr100%) had positive effects on osteoimmunomodulation under the OS microenvironment. Ultimately, the collated findings indicated that the high proportion Sr-doped MAO coatings were more favorable for osteoporosis patients in implant restorations.

Background: Many studies have shown that the size of nanotube (NT) can significantly affect the behavior of osteoblasts on titanium-based materials. But the weak bonding strength between NT and substrate greatly limits their application. Purpose: The objective of this study was to compare the stability of NT and nanopore (NP) coatings, and further prepare antibacterial titanium-based materials by loading LL37 peptide in NP structures. Methods: The adhesion strength of NT and NP layers was investigated using a scratch tester. The proliferation and differentiation of MC3T3-E1 cells on different substrates were evaluated in vitro by CCK8, alkaline phosphatase activity, mineralization and polymerase chain reaction assays. The antibacterial rates of NP and NP/LL37 were also measured by spread plate method. Moreover, the osteogenesis around NP and NP/LL373 in vivo was further evaluated using uninfected and infected models. Results: Scratch test proved that the NP layers had stronger bonding strength with the substrates due to their continuous pore structures and thicker pipe walls than the independent NT structures. In vitro, cell results showed that MC3T3-E1 cells on NP substrates had better early adhesion, spreading and osteogenic differentiation than those of NT group. In addition, based on the drug reservoir characteristics of porous materials, the NP substrates were also used to load antibacterial LL37 peptide. After loading LL37, the antibacterial and osteogenic induction abilities of NP were further improved, thus significantly promoting osteogenesis in both uninfected and infected models. Conclusion: We determined that the NP layers had stronger bonding strength than NT structures, and the corresponding NP materials might be more suitable than NT for preparing drug-device combined titanium implants for bone injury treatment.

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Infection and epithelial downgrowth are major problems associated with maxillofacial percutaneous implants. These complications are mainly due to the improper closure of the implant-skin interface. Therefore, designing a percutaneous implant that better promotes the formation of a stable soft tissue biologic seal around percutaneous sites is highly desirable. Additionally, the fibroblast has been proven to play an important role in the formation of biologic seals. In this study, titania nanotubes were filled with 11.2 kDa C-terminal CCN2 (connective tissue growth factor) fragment, which could exert full CCN2 activity to increase the biological functionality of fibroblasts. This drug delivery system was fabricated on a titanium implant surface. CCN2 was loaded into anodized titania nanotubes using a simplified lyophilization method and the loading efficiency was approximately 80%. Then, the release kinetics of CCN2 from these nanotubes was investigated. Furthermore, the influence of CCN2-loaded titania nanotubes on fibroblast functionality was examined. The results revealed increased fibroblast adhesion at 0.25, 0.5, 1, 2, 4, and 24 hours, increased fibroblast viability over the course of 5 days, as well as enhanced actin cytoskeleton organization on CCN2-loaded titania nanotubes surfaces compared to uncoated, unmodified counterparts. Therefore, the results from this in vitro study demonstrate that CCN2-loaded titania nanotubes have the ability to increase fibroblast functionality and should be further studied as a method of promoting the formation of a stable soft tissue biologic seal around percutaneous sites.

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