Characteristics of large animal models for current cell-based oral tissue regeneration.

Abstract

The recent advances in the field of cell-based therapeutics open promising perspectives for oral tissue regeneration. The development of large animal models, which overcome the limits of the rodent models and allow to emulate clinical situations, is crucial for the validation of regenerative strategies to move towards clinical application. Currently, porcine, canine and ovine models are the mainly developed for oral regeneration and their specific characteristics have an impact on the outcomes of the studies. Thus, this systematic review investigates the application of porcine, canine and ovine models in present cell-based oral regeneration, according to the species characteristics and the targeted tissue to regenerate. A customized search of PubMed, EMBASE, Scopus, and Web of Science databases, from January 2015 to March 2020 was conducted. Relevant articles about cell-based oral tissues engineering in porcine, canine and ovine models were evaluated. Among the evaluated articles, fifty-eight relevant studies about cell-based oral regeneration in porcine, canine and ovine models matched the eligibility criteria and were selected for full analysis. Porcine models, the most similar specie with humans, were mostly used for bone and periodontium regeneration; tooth regeneration was reported only in pig except for one study in dog. Canine models were the most transversal models, successfully involved for all oral tissues regeneration and notably in implantology. However, differences with humans and ethical concerns affect the use of these models. Ovine models, alternative to porcine and canine ones were mainly used for bone and, scarcely, for periodontium regeneration. The anatomy and physiology of these animals restrain their involvement. If consistency was found in defects specificities and cells trends among different species animal models of bone, dentin-pulp complex or tooth regeneration, variability appeared in periodontium. Regeneration assessment methods were more elaborate in porcines and canines than in ovines. Risk of bias was low for selection, attrition and reporting but unclear for performance and detection. Overall, if none of the large animal models can be considered as an ideal one, they are of deemed importance for oral cell-based tissue engineering and researchers should consider their relevance to establish favorable conditions for a given preclinical cell-based therapeutics.