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This study focused on the assessment of radiography, microcomputed tomography, and histology for the evaluation of bone formation in a 15.0-mm defect in the rabbit radius after the implantation of a tissue-engineered construct. Radiography was found to be useful as a noninvasive method for obtaining images of calcified tissue throughout the time course of the experiment. With this method, however, image quality was low, making it difficult to obtain precise information about the location and quantity of the bone formed. Microcomputed tomography was used to create three-dimensional reconstructions of the bone (25-microm resolution). These reconstructions allowed for greater spatial resolution than the radiography, but did not allow for imaging of the implanted scaffold material or the surrounding, nonmineralized tissue. To visualize all materials within the defect area at the cellular level, histology was used. Histological analysis, however, is a destructive technique that did not allow for any further analysis of the samples. Each technique examined here has its own advantages and limitations, but each yields unique information regarding bone regeneration. It is only through the use of all three techniques that complete characterization of the bone growth and tissue/construct responses after implantation in vivo.

Aging induces several types of architectural changes in trabecular bone including thinning, increased levels of anisotropy, and perforation. It has been determined, on the basis of analysis of mathematical models, that reduction in fracture load caused by perforation is significantly higher than those due to equivalent levels of thinning or anisotropy. The analysis has also provided an expression which relates the fractional reduction of strength tau to the fraction of elements nu that have been removed from a network. Further, it was proposed that the ratio Gamma of the elastic constant of a sample and its linear response at resonance can be used as a surrogate for tau. Experimental validation of these predictions requires following architectural changes in a given sample of trabecular bone; techniques to study such changes using microcomputed tomography are only beginning to be available. In the present study, we use anatomically accurate computer models constructed from digitized images of bone samples for the purpose. Images of healthy bone are subjected to successive levels of synthetic degradation via surface erosion. Computer models constructed from these images are used to calculate their fracture load and other mechanical properties. Results from these computations are shown to be consistent with predictions derived from the analysis of mathematical models. Although the form of tau(nu) is known, parameters in the expression are expected to be sample-specific, and hence nu is not a reliable predictor of strength. We provide an example to demonstrate this. In contrast, analysis of model networks shows that the linear part of tau(Gamma) depends only on the structure of trabecular bone. Computations on models constructed from samples of iliac crest trabecular bone are shown to be in agreement with this assertion. Since Gamma can be computed from a vibrational assessment of bone, we argue that the latter can be used to introduce new surrogates for bone strength and hence diagnostic tools for osteoporosis.

Osteoporosis-related bone damage causes major socioeconomic problems. For efficient use of therapeutic agents, it is necessary to be able to reliably identify patients with high propensity for nontraumatic fracture. Age-related bone loss imposes several architectural changes in bone; one of the few ways to estimate damage due to individual changes, and hence determine the most serious types of damage, is via the analysis of suitable mathematical models. Anatomical sites such as the vertebral body, proximal femur, and distal radius are locations where most age-related fractures occur. The inner porous (or trabecular) bone from these sites, which resemble disordered cubic networks, play a significant role in load transmission at these sites. Analysis of a mathematical model of porous bone is used to show that perforation of elements of the network is the most damaging architectural change to a bone. We also show that an expression for bone strength, derived on this basis, can capture changes in strength caused by the inclusion of other features like thinning of trabecular bone and the anisotropy of the network. We finally argue that bone density, which is currently the most routinely used diagnostic, cannot be a reliable surrogate for bone strength.

Tissue engineering combines the aspects of cell biology, engineering, material science, and surgery to generate new functional tissue, and provides an important approach to the repair of segmental defects and in restoring biomechanical function. The development of tissue-engineering strategies into clinical therapeutic protocols requires extensive, preclinical experimentation in appropriate animal models. The ultimate success of any treatment strategy must be established in these animal models before clinical application. It is clear that the demands of the biological and mechanical environment in the clinical repair of critical size defects with tissue-engineered materials is significantly different from those existing in experimental animals. The major considerations facing any tissue-engineering testing logic include the choice of the defect, the animal, the age of the animal, the anatomic site, the size of the lesion, and most importantly, the micro-mechanical environment. With respect to biomechanical considerations when selecting animals for tissue- engineering of bone, it is evident that no common criteria have been reported. While in smaller animals due to size constraint only structural properties of whole bones can be measured, in larger animals and humans both material properties and structural properties are of interest. Based on reported results, comparison between the tissue-engineered bone across species may be of importance in establishing better model selection criteria. It has already been found that the deformation of long bones is fairly constant across species, and that stress levels during gait are dependent on the weight of the animal and the material properties of the bone tissue. Future research should therefore be geared towards developing better biomechanical testing systems and then finding the right animal model for the existing equipment.