Bone fracture healing in mechanobiological modeling: A review of principles and methods

•Bone fracture healing is a series of biological processes, regulated by the mechanical environment and biological factors.•Conceptual models of bone fracture healing aim to understand the qualitative process and to formulate its general mechanism.•Mechanobiological models consider the effects of both mechanical environment and biological factors.•Mechanobiological regulations and mechanical stimuli effects on growth factors can potentially have clinical applications.•While important, the inflammatory phase in the bone healing process is not included in mechanobiological simulations.

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.