title: Computational simulation of fracture healing: influence of interfragmentary movement on the callus growth.
abstract: Bone fractures heal through a complex process involving several cellular events. This healing process can serve to study factors that control tissue growth and differentiation from mesenchymal stem cells. The mechanical environment at the fracture site is one of the factors influencing the healing process and controls size and differentiation patterns in the newly formed tissue. Mathematical models can be useful to unravel the complex relation between mechanical environment and tissue formation. In this study, we present a mathematical model that predicts tissue growth and differentiation patterns from local mechanical signals. Our aim was to investigate whether mechanical stimuli, through their influence on stem cell proliferation and chondrocyte hypertrophy, predict characteristic features of callus size and geometry. We found that the model predicted several geometric features of fracture calluses. For instance, callus size was predicted to increase with increasing movement. Also, increases in size were predicted to occur through increase in callus diameter but not callus length. These features agree with experimental observations. In addition, spatial and temporal tissue differentiation patterns were in qualitative agreement with well-known experimental results. We therefore conclude that local mechanical signals can probably explain the shape and size of fracture calluses.
authors.affiliation: Group of Structural Mechanics and Material Modelling (GEMM), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Spain. jmgaraz@unizar.es
authors.forename: J M
authors.initials: JM
authors.lastname: García-Aznar
authors.forename: J H
authors.initials: JH
authors.lastname: Kuiper
authors.forename: M J
authors.initials: MJ
authors.lastname: Gómez-Benito
authors.forename: M
authors.initials: M
authors.lastname: Doblaré
authors.forename: J B
authors.initials: JB
authors.lastname: Richardson
mesh_terms: D002146:Bony Callus / Q000166:cytology / Q000254:growth & development*; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology; D020342:Finite Element Analysis; D017102:Fracture Healing / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008954:Models, Biological; D009068:Movement / Q000502:physiology*; D013997:Time Factors