This review provides an overview of animal models for the evaluation, comparison, and systematic optimization of tissue engineering and regenerative medicine strategies related to bone tissue. This review includes an overview of major factors that influence the rational design and selection of an animal model. A comparison is provided of the 10 mammalian species that are most commonly used in bone research, and existing guidelines and standards are discussed. This review also identifies gaps in the availability of animal models: (1) the need for assessment of the predictive value of preclinical models for relative clinical efficacy, (2) the need for models that more effectively mimic the wound healing environment and mass transport conditions in the most challenging clinical settings (e.g., bone repair involving large bone and soft tissue defects and sites of prior surgery), and (3) the need for models that allow more effective measurement and detection of cell trafficking events and ultimate cell fate during the processes of bone modeling, remodeling, and regeneration. The ongoing need for both continued innovation and refinement in animal model systems, and the need and value of more effective standardization are reinforced.

The spindle checkpoint monitors mitotic spindle integrity and the attachment of kinetochores to the spindle. Upon sensing a defect the checkpoint blocks cell cycle progression and thereby prevents chromosome missegregation. Previous studies in budding yeast show that the activated spindle checkpoint inhibits the onset of anaphase by an unknown mechanism. One possible target of the spindle checkpoint is anaphase promoting complex (APC), which controls all postmetaphase events that are blocked by spindle checkpoint activation. We have isolated mad2, a spindle checkpoint component in fission yeast, and shown that mad2 overexpression activates the checkpoint and causes a cell cycle arrest at the metaphase-to-anaphase transition. In addition to the observation that mad2-induced arrest can be partially relieved by mitosis-promoting factor inactivation, we present genetic evidence consistent with the hypothesis that the spindle checkpoint imposes a cell cycle arrest by inhibiting APCdependent proteolysis.

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Three-dimensional assessment of glenoid anatomy and implant templating and the use of these images at the time of surgery improve the surgeon's ability to place the glenoid implant in the desired location.

This study tested the hypothesis that pulsed electromagnetic field (PEMF) treatments augment and accelerate the healing of bone trauma. It utilized micro-computed tomography imaging of live rats that had received bilateral 0.2 mm fibular osteotomies (-0.5% acute bone loss) as a means to assess the in vivo rate dynamics of hard callus formation and overall callus volume. Starting 5 days post-surgery, osteotomized right hind limbs were exposed 3 h daily to Physio-Stim@ PEMF, 7 days a week for up to 5 weeks of treatment. The contralateral hind limbs served as sham-treated, within-animal internal controls. Although both PEMF-and sham-treatment groups exhibited similar onset of hard callus at -9days after surgery, a 2-fold faster rate of hard callus formation was observed thereafter in PEMF-treated limbs, yielding a 2-fold increase in callus volume by 13-20 days after surgery. The quantity of the new woven bone tissue within the osteotomy sites was significantly better in PEMF-treated versus sham-treated fibulae as assessed via hard tissue histology. The apparent modulus of each callus was assessed via a cantilever bend test and indicated a 2-fold increase in callus stiffness in the PEMF-treated over sham-treated fibulae. PEMF-treated fibulae exhibited an apparent modulus at the end of 5-weeks that was -80% that of unoperated fibulae. Overall, these data indicate that Physio-Stim@ PEMF treatment improved osteotomy repair. These beneficial effects on bone healing were not observed when a different PEMF waveform, Osteo-Stim@, was used. This latter observation demonstrates the specificity in the relationship between waveform characteristics and biological outcomes.

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The B3 and C2 patterns have qualitative and quantitative differences that may result in different clinical outcomes than classic B2 or C types; therefore, our findings suggest that these new subtypes should be included in a new or modified classification system.