A surprisingly poor correlation betweenin vitroandin vivotesting of biomaterials for bone regeneration: results of a multicentre analysis
1 Bone and Joint Research Group, Centre for Human Development Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, UK
2 Department of Surgical Sciences, Orthopedics, Institute of Medicine, Uppsala University, Sweden
3 Institute for Biomechanics, Swiss Federal Institute of Technology Zurich (ETHZ), Vladimir-Prelog-Weg 3, Zurich, 8093, Switzerland
4 Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, Eindhoven, 5600MB, The Netherlands
5 Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, Eindhoven, 5600MB, The Netherlands
6 AO Research Institute Davos, Davos Platz, Switzerland
7 Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUV A Research Centre, Austrian Cluster for Tissue Regeneration, European Institute of Excellence on Tissue Engineering and Regenerative Medicine Research (Expertissues EEIG) Vienna-Branch, Vienna, Austria
8 Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, UK
9 University College London, Tissue Repair and Engineering Centre, Institute of Orthopaedics, Stanmore Campus, London, UK
10 Plymouth University, Peninsula School of Medicine and Dentistry, Plymouth, UK
11 University College London, Eastman Dental Institute, London, UK
12 Department of Chemistry, A Science for Life Laboratory, Polymer Chemistry Division, Uppsala University, Uppsala, Sweden
Ψ These authors equally contributed to this paper
Abstract
New regenerative materials and approaches need to be assessed through reliable and comparable methods for rapid translation to the clinic. There is a considerable need for provenin vitroassays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained throughin vivostudies. The purpose of this multicentre review was to investigate the correlation between existingin vitroresults within vivooutcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36in vivostudies and 47in vitroassays testing 93 different biomaterials. The outcomes of thein vitroandin vivoexperiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation ofin vitrowithin vivoscores for each assay alone and in combination was assessed. A surprisingly poor correlation betweenin vitroandin vivoassessments of biomaterials was revealed indicating a clear need for further development of relevantin vitroassays. There was no significant overall correlation betweenin vitroandin vivooutcome. The meanin vitroscores revealed a trend of covariance toin vivoscore with 58 %. The inadequacies of the currentin vitroassessments highlighted here further stress the need for the development of novel approaches toin vitrobiomaterial testing and validated pre-clinical pipelines.
Keywords
- in vivo
- in vitro
- correlation
- biomaterials
- multicentre study
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