Abstract
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These principles are expanded and applied to the field of regenerative medicine by Birkenfeld et al. (page 842) and can also be seen in action in multiple ways in this issue. As an example, multiple reviews are included that summarize the strengths and weakness of each animal model, and/or each application; this will assist investigators with proper selection of the model to address specific questions resulting in both reduction of animal use and refinement of the animal models. For instance, Dunn et al. (page 829) discuss in depth the use of the ovine models for meniscus tissue engineering and provide guidelines for improving the model. Similarly, Pascual et al. (page 863) describe the use of the New Zealand rabbit as a model for tissue repair of the abdominal wall, Wan et al. (page 971) examine the use of a murine model for calvarial defects, and Assman et al. (page 982) use rats for assessing vulvular and vascular grafts.
Orefoo et al. (page xxx) directly address the reduction, replacement, and refinement principle by reviewing the use of the avian chorioallantoic membrane assay as a way to rapidly prescreen new treatments before moving to more complex animal models. Finally, Fawzy El-Sayed et al. (page 900) and Westhauser et al. (page 881) review the strengths and weaknesses of multiple animal models and experimental approaches as applied to periodontal diseases and evaluation of bone substitutes, respectively. All these reviews provide critical information that will assist other investigators in selecting the most appropriate animal models for the question being addressed and will, at the end, result in optimal application of the 3R guiding principles of animal experimentation.
In addition to these excellent and timely reviews, this issue also describes new models being developed for particular applications. These include pigs (Caballero et al., page 889) and rabbits (Birkenfel et al., page 842) as models to address defects in the palate and mandible, respectively, and murine models of progressive orthopedic wear (Pajarinen et al., page 1003), ischemia-impaired wound healing (Hofmann et al., page 995), and 3D fat volume evaluation by microcomputed tomography (Berndt et al., page 964). Two articles describe the effects of age on the effectiveness of treatments for aortic valve replacement using a sheep model (Theodoridis et al., page 953) and muscle injury using a rat model (Criswell et al., page 1012).
Finally, a concept article by Williams (page 926) proposes the use of an algorithm that generates biocompatibility, functionality, and tissue incorporation data with the goal of streamlining the tissue engineering processes from conceptualization to clinical application. This approach, combining data analytics with “traditional” bench experimentation, which now commonly includes one or more “omics” components, is likely to become an integral part of the field tissue engineering from a research and development perspective as well as a regulatory perspective. The end result being a more efficient system with lower failure rates as well as a reduction in the number of animals being used to achieve a set objectives.
Combined, all the articles and reviews in Part I and Part II of the special issue of “Animal Models in Tissue Engineering” will assist investigators with making optimal informed decisions that results not only in faster, more efficient, translation of basic observations into clinical improvements but also in strengthening and supporting the principles of reduction, replacement, and refinement of animal models.