title: Bone fracture healing in mechanobiological modeling: A review of principles and methods.
abstract: Bone fracture is a very common body injury. The healing process is physiologically complex, involving both biological and mechanical aspects. Following a fracture, cell migration, cell/tissue differentiation, tissue synthesis, and cytokine and growth factor release occur, regulated by the mechanical environment. Over the past decade, bone healing simulation and modeling has been employed to understand its details and mechanisms, to investigate specific clinical questions, and to design healing strategies. The goal of this effort is to review the history and the most recent work in bone healing simulations with an emphasis on both biological and mechanical properties. Therefore, we provide a brief review of the biology of bone fracture repair, followed by an outline of the key growth factors and mechanical factors influencing it. We then compare different methodologies of bone healing simulation, including conceptual modeling (qualitative modeling of bone healing to understand the general mechanisms), biological modeling (considering only the biological factors and processes), and mechanobiological modeling (considering both biological aspects and mechanical environment). Finally we evaluate different components and clinical applications of bone healing simulation such as mechanical stimuli, phases of bone healing, and angiogenesis.
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Ghiasi
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Vaziri
authors.affiliation: Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Rodriguez
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Ara
authors.initials: A
authors.lastname: Nazarian
keywords: Angiogenesis; Biological modeling; Bone fracture healing; Callus; Computational modeling; Finite element; Growth factors; Hematoma; Mathematical modeling; Mechanical stimuli; Mechanobiological modeling