title: Occurrence and treatment of bone atrophic non-unions investigated by an integrative approach.
abstract: Recently developed atrophic non-union models are a good representation of the clinical situation in which many non-unions develop. Based on previous experimental studies with these atrophic non-union models, it was hypothesized that in order to obtain successful fracture healing, blood vessels, growth factors, and (proliferative) precursor cells all need to be present in the callus at the same time. This study uses a combined in vivo-in silico approach to investigate these different aspects (vasculature, growth factors, cell proliferation). The mathematical model, initially developed for the study of normal fracture healing, is able to capture essential aspects of the in vivo atrophic non-union model despite a number of deviations that are mainly due to simplifications in the in silico model. The mathematical model is subsequently used to test possible treatment strategies for atrophic non-unions (i.e. cell transplant at post-osteotomy, week 3). Preliminary in vivo experiments corroborate the numerical predictions. Finally, the mathematical model is applied to explain experimental observations and identify potentially crucial steps in the treatments and can thereby be used to optimize experimental and clinical studies in this area. This study demonstrates the potential of the combined in silico-in vivo approach and its clinical implications for the early treatment of patients with problematic fractures.
authors.affiliation: Division of Biomechanics and Engineering Design, Department of Mechanical Engineering, Katholieke Universiteit Leuven, Leuven, Belgium. liesbet.geris@mech.kuleuven.be
authors.forename: Liesbet
authors.initials: L
authors.lastname: Geris
authors.forename: Anita A C
authors.initials: AA
authors.lastname: Reed
authors.forename: Jos
authors.initials: J
authors.lastname: Vander Sloten
authors.forename: A Hamish R W
authors.initials: AH
authors.lastname: Simpson
authors.forename: Hans
authors.initials: H
authors.lastname: Van Oosterwyck
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D001861:Bone Regeneration / Q000502:physiology*; D001842:Bone and Bones / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D017690:Cell Transplantation; D020219:Chondrogenesis / Q000502:physiology; D003198:Computer Simulation; D004195:Disease Models, Animal; D050723:Fractures, Bone / Q000503:physiopathology / Q000628:therapy*; D006651:Histocytochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D018709:Statistics, Nonparametric; D014945:Wound Healing / Q000502:physiology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D018809:Proliferating Cell Nuclear Antigen
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