title: The rational use of animal models in the evaluation of novel bone regenerative therapies.
abstract: Bone has a high potential for endogenous self-repair. However, due to population aging, human diseases with impaired bone regeneration are on the rise. Current strategies to facilitate bone healing include various biomolecules, cellular therapies, biomaterials and different combinations of these. Animal models for testing novel regenerative therapies remain the gold standard in pre-clinical phases of drug discovery and development. Despite improvements in animal experimentation, excessive poorly designed animal studies with inappropriate endpoints and inaccurate conclusions are being conducted. In this review, we discuss animal models, procedures, methods and technologies used in bone repair studies with the aim to assist investigators in planning and performing scientifically sound experiments that respect the wellbeing of animals. In the process of designing an animal study for bone repair investigators should consider: skeletal characteristics of the selected animal species; a suitable animal model that mimics the intended clinical indication; an appropriate assessment plan with validated methods, markers, timing, endpoints and scoring systems; relevant dosing and statistically pre-justified sample sizes and evaluation methods; synchronization of the study with regulatory requirements and additional evaluations specific to cell-based approaches. This article is part of a Special Issue entitled "Stem Cells and Bone".
authors.affiliation: University of Zagreb School of Medicine, Center for Translational and Clinical Research, Department for Intercellular Communication, Salata 2, Zagreb, Croatia. Electronic address: mihaela.peric@mef.hr.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Peric
authors.affiliation: University of Zagreb School of Medicine, Center for Translational and Clinical Research, Laboratory for Mineralized Tissues, Salata 11, Zagreb, Croatia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Dumic-Cule
authors.affiliation: University of Zagreb School of Medicine, Department of Physiology and Immunology, Salata 3, Zagreb, Croatia.
authors.forename: Danka
authors.initials: D
authors.lastname: Grcevic
authors.affiliation: University of Zagreb School of Medicine, Center for Translational and Clinical Research, Department for Intercellular Communication, Salata 2, Zagreb, Croatia.
authors.forename: Mario
authors.initials: M
authors.lastname: Matijasic
authors.affiliation: University of Zagreb School of Medicine, Center for Translational and Clinical Research, Department for Intercellular Communication, Salata 2, Zagreb, Croatia.
authors.forename: Donatella
authors.initials: D
authors.lastname: Verbanac
authors.affiliation: Paul Regulatory Services Ltd, Fisher Hill Way, Cardiff CF15 8DR, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Paul
authors.affiliation: University of Zagreb School of Medicine, Center for Translational and Clinical Research, Laboratory for Mineralized Tissues, Salata 11, Zagreb, Croatia.
authors.forename: Lovorka
authors.initials: L
authors.lastname: Grgurevic
authors.affiliation: University of Zagreb School of Medicine, Department of Pharmacology, Salata 11, Zagreb, Croatia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trkulja
authors.affiliation: Pfizer Inc., Global Research and Development, Global Science and Technology, 100 Eastern Point Road, Groton, CT 06340, USA.
authors.forename: Cedo M
authors.initials: CM
authors.lastname: Bagi
authors.affiliation: University of Zagreb School of Medicine, Center for Translational and Clinical Research, Laboratory for Mineralized Tissues, Salata 11, Zagreb, Croatia. Electronic address: vukicev@mef.hr.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Vukicevic
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D044968:Regenerative Medicine / Q000379:methods*; D013223:Statistics as Topic; D014945:Wound Healing / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials
keywords: Animal model; Bone fracture; Bone healing; Healing parameters; Regenerative therapy; Tools for scoring