For the determination of key factors or devices that promote periodontal regeneration, preclinical investigations using in vivo animal models are critical for evaluating the biological responses before human clinical trial testing. In this chapter, we provide an overview on the commonly used preclinical animals for the study of reconstructive procedures to promote bone and soft tissue repair of tooth-supporting periodontal defects. Steps are provided on the animal management for evaluation of outcome measures using descriptive histology, histomorphometry, three-dimensional imaging, and safety assessments. The use of these key measures of periodontal regeneration should aid investigators in the selection of appropriate surrogate endpoints to be utilized in the clinical arena, which are not practical or ethical in humans. These methods will prepare investigators and assist them in identifying endpoints that can then be adapted to human clinical trial planning.
[Show abstract][Hide abstract] ABSTRACT: In humans, microbially induced inflammatory periodontal diseases are the primary initiators that disrupt the functional and structural integrity of the periodontium (i.e., the alveolar bone, the periodontal ligament, and the cementum). The reestablishment of its original structure, properties, and function constitutes a significant challenge in the development of new therapies to regenerate tooth-supporting defects. Preclinical models represent an important in vivo tool to critically evaluate and analyze the key aspects of novel regenerative therapies, including (1) safety, (2) effectiveness, (3) practicality, and (4) functional and structural stability over time. Therefore, these models provide foundational data that supports the clinical validation and the development of novel innovative regenerative periodontal technologies. Steps are provided on the use of the root fenestration animal model for the proper evaluation of periodontal outcome measures using the following parameters: descriptive histology, histomorphometry, immunostaining techniques, three-dimensional imaging, electron microscopy, gene expression analyses, and safety assessments. These methods will prepare investigators and assist them in identifying the key end points that can then be adapted to later stage human clinical trials.
Daniel E Spratt, Michael J Evans, Brian J Davis, Michael G Doran, Man Xia Lee, Neel Shah, John Wongvipat, Kathyrn E Carnazza, George G Klee, William Polkinghorn, Donald J Tindall, Jason S Lewis, Charles L Sawyers
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