Correlation between molecular signals and bone bonding to titanium implants

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A better understanding of the biological processes controlling osseointegration at the bone-to-implant interface is needed. The aim of this study was to examine which are the molecular and biochemical variables that are significantly related to osseointegration, using multiple regression analysis.

Materials and methods

Titanium coins were placed into the tibial cortical bone of New Zealand White rabbits and evaluated using pull-out test after 4 and 8 weeks of healing. Correlations between pull-out and several markers from tissue fluid (Lactate dehydrogenase [LDH] and Alkaline phosphatase [ALP] activities and total protein content) and peri-implant bone tissue (total protein, RNA and DNA content, implant area covered with bone and gene expression of osteoblast, osteoclast and inflammation markers) were used to assess the importance of these parameters in bone healing and in relation to implant performance.


Our results showed a negative correlation between the content of DNA, RNA and total protein at the peri-implant bone tissue and the pull-out force, indicating that as bone matures and implant becomes more osseointegrated, the organic content of bone decreases. The negative correlation found between pull-out force and ALP activity pointed to a delayed healing in implants with lower pull-out values and primary mineralization still ongoing. LDH activity and total protein content in the tissue fluid were as well negatively correlated with the pull-out force. Finally, a positive correlation was observed between the pull-out force and the expression of the osteoblast and the bone resorption markers, being osteocalcin and collagen-I the best predictive markers for osseointegration after 4 and 8 weeks of healing respectively.


These results suggest that the evaluation of these markers could be relevant for the assessment of new implant surfaces for rapid bone healing and improved implant performance.

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