title: A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration: results of a multicentre analysis.
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 proven in vitro assays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained through in vivo studies. The purpose of this multicentre review was to investigate the correlation between existing in vitro results with in vivo outcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36 in vivo studies and 47 in vitro assays testing 93 different biomaterials. The outcomes of the in vitro and in vivo experiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation of in vitro with in vivo scores for each assay alone and in combination was assessed. A surprisingly poor correlation between in vitro and in vivo assessments of biomaterials was revealed indicating a clear need for further development of relevant in vitro assays. There was no significant overall correlation between in vitro and in vivo outcome. The mean in vitro scores revealed a trend of covariance to in vivo score with 58 %. The inadequacies of the current in vitro assessments highlighted here further stress the need for the development of novel approaches to in vitro biomaterial testing and validated pre-clinical pipelines.
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK.roco@soton.ac.uk.
authors.forename: G
authors.initials: G
authors.lastname: Hulsart-Billström
authors.forename: J I
authors.initials: JI
authors.lastname: Dawson
authors.forename: S
authors.initials: S
authors.lastname: Hofmann
authors.forename: R
authors.initials: R
authors.lastname: Müller
authors.forename: M J
authors.initials: MJ
authors.lastname: Stoddart
authors.forename: M
authors.initials: M
authors.lastname: Alini
authors.forename: H
authors.initials: H
authors.lastname: Redl
authors.forename: A
authors.initials: A
authors.lastname: El Haj
authors.forename: R
authors.initials: R
authors.lastname: Brown
authors.forename: V
authors.initials: V
authors.lastname: Salih
authors.forename: J
authors.initials: J
authors.lastname: Hilborn
authors.forename: S
authors.initials: S
authors.lastname: Larsson
authors.forename: R O
authors.initials: RO
authors.lastname: Oreffo
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D006801:Humans; D008422:Materials Testing / Q000379:methods*; D051379:Mice; D051381:Rats
chemical_list: D001672:Biocompatible Materials