Rodent models in bone-related research: the relevance of calvarial defects in the assessment of bone regeneration strategies

Abstract

In vivo research with animal models has been a preferred experimental system in bone-related biomedical research since, by approximation, it allows relevant data gathering regarding physiological and pathological conditions that could be of use to establish more effective clinical interventions. Animal models, and more specifically rodent models, have been extensively used and have contributed greatly to the development and establishment of a wide range of translational approaches aiming to regenerate the bone tissue. In this regard, the calvarial defect model has found great application in basic and applied research, nonetheless the controversial rationalization for the use of critical size defects -defects that are unable to report spontaneous healing -or subcritical size defects in the proposed applications. Accordingly, this work aims to review the advantages and limitations of the use of rodent models in biomedical bone-related research, emphasizing the problematic issues of the use of calvarial critical and subcritical size defects. Additionally, surgical protocols for the establishment of both defects in rat calvarial bone, as well as the description and exemplification of the most frequently used techniques to access the bone tissue repair, are portrayed.

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…The first determinant depends on the availability of an animal model that mimics a human disease involving bone repair so that the data generated can be used to predict the drug efficacy and safety in patients. Examples of animal models with good predictability of clinical outcomes include models of postmenopausal osteoporosis [87][88][89][90][91][92], models of glucocorticoid induced bone loss [93][94][95][96], models of cancer metastasis to bone [97], disuse models [98,99], fracture healing models [100][101][102][103] and several others. The second determinant of successful experimentation relates to translational biomarkers of novel therapy efficacy and safety that can be accurately predicted and monitored in patients.…”

“…Of all laboratory animals mice and rats are considered to have skeletons and bone biologies that are least similar to humans since their skeletons are modelling-driven due to permanently open growth plates at the epiphyses of long bones, a lack of the Haversian system and low cancellous bone content at the epiphyses of the long bones [100,[130][131][132][133][134][135][136]. However, studies in rodents are very informative and cost effective.…”

Raman spectroscopy of bone composition during healing of subcritical calvarial defects

“…After 14 days of healing the bone strength was recovered. Besides studies on limbs bones, calvarial bone defects have gained an extensive reputation amongst the available orthotropic models [16]. Calvaria are the flat bones that comprise the skull.…”

In vivo reference point indentation measurement variability in skeletally mature inbred mice

“…Rodents are the most common animals used in skeletal research, owing in large part to the biological tools (for example, genetic manipulation) available for these taxa. 10,11 Using rodent models allows for controlled experimental studies, which provide the foundation for preclinical studies in larger animal models with bone that better approximates human morphology (that is, dog, pig and/or monkey).…”