Development of a quantitative preclinical screening model for implant osseointegration in rat tail vertebra.

OBJECTIVES: Functional tooth replacement and bone regeneration are parts of the daily practice in modern dentistry, but well-reproducible and relatively inexpensive experimental models are still missing. We aimed to develop a new small animal model to monitor osseointegration utilizing the combination of multiple evaluation protocols. MATERIAL AND METHODS: After cutting the tail between the C4 and C5 vertebrae in Wistar rats, costume made, parallel walled, non-threaded implants were placed into the center of the tail parallel with its longitudinal axis using a surgical guide. Osseointegration of the titanium implants was followed between 4 and 16 weeks after surgery applying axial extraction force, and resonance frequency analysis as functional tests, and histomorphometry and micro-CT as structural evaluations. RESULTS: In functional tests, we observed that both methods are suitable for the detection of the time-dependent increase in osseointegration, but the sensitivity of the pull-out technique (an approximately five times increase with rather low standard error) was much higher than that of the resonance frequency analysis. In structural evaluations, changes in the detected bone implant contact values measured by histomorphometry (yielding 1.5 times increase, with low variations of data) were more reliable than micro-CT based evaluations to screen the developments of contact between bone and implant. CONCLUSION: Our results provide evidence that the caudal vertebrae osseointegration model is useful for the preclinical evaluation of implant integration into the bone. CLINICAL RELEVANCE: The combination of the biomechanical and structural tests offers a well-reproducible small animal system that can be suitable for studying the integration of various implant materials and surface treatments.

Effect of stem cells of dental pulp origin on osseointegration of titanium implant in a novel rat vertebra model.

During that last decade a large number of experiments showed the successful application of stem cells in achieving large bone volume regeneration. On the contrary, our knowledge about the promotion of implant osseointegration by stem cell is sporadic. Recently, our research group has carried out an array of studies aiming the characterization of postnatal stem cells of dental origin. In addition, we have developed a novel quantitative model for implant osseointegration in rat tail vertebrae. In the present work we aimed to study how the implant osseointegration process is affected by mesenchymal stem cells of rat dental pulp origin (DPSC) when cells are undifferentiated or predifferentiated into osteogenic direction. Our results show that undifferentiated pulp cells inserted between the implant and the bone slow down the osseointegration process. On the other hand, pre-differentiated DPSCs do not have a similar adverse effect any more. Our data suggest that the success of mesenchymal stem cell application to promote implant osseointegration is highly dependent on the applied conditions, particularly on the parallel applicatioh of scaffolds and osteogenic components.

Aminobisphosphonate stimulates bone regeneration and enforces consolidation of titanium implant into a new rat caudal vertebrae model.

Bisphosphonates are widely used as therapeutic agents in bone disorders including cancer metastasis due to their osteoclast inhibitory effect. Recent data shows that bisphosphonates may also induce bone-building by stimulating osteoblast activity. Clinical observations, however, have revealed that bisphosphonates may cause necrosis in the oral cavity which questions their usefulness in bone regeneration during the consolidation of inorganic implants. Here we report the investigation of bone neogenesis following chronic amine bisphosphonate (Zometa) treatment in a novel experimental model, using the rat tail vertebra as a support. This method involves (1) implantation of titan screw into the tail vertebrae, (2) systemic bisphosphonate treatment and (3) quantitative biophysical measurements which mirrors consolidation of implant, i.e. strength of fixation and changes in newly formed bone architecture using micro Computer Tomograph (micro-CT). The degree of fixation of titan implants (osseointegration) increased by 36% on the effect of Zometa and the structure of newly formed bone became robust. The mass of new bone increased 3.1-fold at 6 weeks of regeneration, as compared to controls. Thus, Zometa, a potent aminobisphosphonate used in therapy of cancer metastases, osteoporosis and bone marrow transplantation, significantly increased bone neogenesis and enforced osseointegration of titan implants as measured quantitatively in the rat tail vertebra. Our data support the usefulness of aminobisphosphonates in the rehabilitation of bone loss as well as in improvement osseointegration of implants. We emphasise that this novel method may open up new possibilities for screening the effects of local and systemic treatments.