Evaluation of Preclinical Models for the Testing of Bone Tissue-Engineered Constructs

Tissue Eng Part C Methods. 2020 Feb;26(2):107-117. doi: 10.1089/ten.TEC.2019.0213. Epub 2020 Jan 13.

Abstract

Autologous bone grafting is the clinical gold standard for the treatment of large bone defects, but it can only be obtained in limited amounts and is associated with donor site morbidity. These challenges might be overcome by tissue engineering (TE). Although promising results have been reported, translation into clinics often fails. Lack of reproducibility in preclinical studies may be one of the reasons. We evaluated preclinical models for testing of novel TE strategies, as well as the perception of researchers and clinicians toward the models. Therefore, a review of publications on preclinical models of the past 10 years was performed. A survey addressed to both clinicians and scientists was conducted to assess the clinical need for bone tissue engineering (BTE) constructs and researchers were asked about their satisfaction with the currently available preclinical models. A literature review revealed 169 articles on in vivo studies in the field of BTE, including 26 studies utilizing large animal models and 143 studies in small animals, with rabbits and rats presenting the most commonly used species. Only a few studies used skeletally mature animals, which is in large contrast to the patients targeted. The localization of the bone defects varied, but the vast majority (60%) were segmental bone defects with various fixation techniques. Results of 70 surveys confirmed a great clinical need for TE constructs and positive perceptions of all participants toward its future clinical application. Nevertheless, the need for optimization of preclinical models and limitations when it comes to translation of results to the clinical situation were indicated. No clear trends were detected with regards to the preclinical model, leading to most satisfying results despite the trend that scientists rated generally large animal models higher than small animal models. Results of the literature review and the survey reveal the lack of standardized methods. Despite the affirmed clinical need as well as a very positive perception of clinicians toward the use of TE, results indicate a critical need to optimize preclinical models and, in particular, improve translational aspects of the models. A consensus in the field on a limited number of well-standardized models should be reached.

Keywords: animal models; bone tissue engineering; preclinical models.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Diseases / therapy*
  • Bone Transplantation
  • Bone and Bones / cytology*
  • Evaluation Studies as Topic
  • Humans
  • Models, Animal*
  • Osteogenesis*
  • Tissue Engineering / instrumentation
  • Tissue Engineering / methods*
  • Tissue Engineering / trends
  • Tissue Scaffolds / chemistry*