Affiliation:
1. Orthopaedic Biomechanics and Institute for Complex Molecular Systems (ICMS) Department of Biomedical Engineering Eindhoven University of Technology P.O. Box 513 Eindhoven 5600 MB The Netherlands
2. Department of Regenerative Biomaterials Radboud Institute for Molecular Life Sciences Radboud University Medical Center P.O. Box 9101 Nijmegen 6525 GA The Netherlands
Abstract
AbstractHuman in vitro bone remodeling models, using osteoclast–osteoblast cocultures, can facilitate the investigation of human bone remodeling while reducing the need for animal experiments. Although current in vitro osteoclast–osteoblast cocultures have improved the understanding of bone remodeling, it is still unknown which culture conditions support both cell types. Therefore, in vitro bone remodeling models can benefit from a thorough evaluation of the impact of culture variables on bone turnover outcomes, with the aim to reach balanced osteoclast and osteoblast activity, mimicking healthy bone remodeling. Using a resolution III fractional factorial design, the main effects of commonly used culture variables on bone turnover markers in an in vitro human bone remodeling model are identified. This model is able to capture physiological quantitative resorption–formation coupling along all conditions. Culture conditions of two runs show promising results: conditions of one run can be used as a high bone turnover system and conditions of another run as a self‐regulating system as the addition of osteoclastic and osteogenic differentiation factors is not required for remodeling. The results generated with this in vitro model allow for better translation between in vitro studies and in vivo studies, toward improved preclinical bone remodeling drug development.
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
Reference68 articles.
1. Animal models are essential to biological research: issues and perspectives
2. D.Thomas D.Chancellor A.Micklus S.LaFever M.Hay S.Chaudhuri R.Bowden A. W.Lo Clinical Development Success Rates and Contributing Factors 2011–2020 Informa Pharma Intelligence2021.
3. D. W.Thomas J.Burns J.Audette A.Carroll C.Dow‐Hygelund M.Hay Clinical Development Success Rates 2006–2015 BIO Industry Anal2016 1 16.
4. In vitro Models of Bone Remodelling and Associated Disorders
5. The Three Rs: The Way Forward
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献