Bone fracture is a very common 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 has been employed to understand its mechanisms, to investigate specific clinical questions, and to design healing strategies.
In chapter 1, a review of the biology and mechanobiology of bone fracture repair was provided. A comparison of different methodologies of bone healing simulation was performed that included conceptual modeling (qualitative modeling of bone healing to understand the general concepts and mechanisms), biological modeling (considering only the biological factors and processes), and mechanobiological modeling (considering both biological aspects and mechanical environment). Important factors and mechanisms in mechanobiological models such as mechanical stimuli, bone healing phases already included in simulation, and angiogenesis were highlighted in the literature survey. Clinical applications of bone healing simulations and the current restrictions were also assessed in the literature survey. Two major issues were raised by this literature survey, which would be addressed by the computational and/or experimental studies in chapter 2-4:
- The initial phase of healing has been neglected in the bone healing simulation studies.
- There have been limitations in clinical application of bone healing simulations and there exists a quite long journey from bone healing simulations to clinical applications.
In chapter 2, a parametric computational study was conducted to explore the importance of the initial phase of bone healing in mechanobiological modeling. To that end, bone healing process was simulated in models with different diffusion coefficients of mesenchymal stem cells, granulation tissue Young’s moduli, callus geometries, and interfragmentary gap sizes. It was assumed that these parameters modulated the outcome of bone healing during its initial phase, which involves inflammatory response, hematoma evolution to form granulation tissue and initial callus development during the first few days post-fracture.
Findings from the literature review and the computational parametric study motivated us to conduct a comprehensive animal study on the initial phase of bone healing in chapter 3. Several s experimental tests, including atomic force microscopy, micro computational tomography, histology, and reverse transcription polymerase chain reaction analysis were performed on 72 healthy young rats in order to provide quantitative data on the initial phase of bone healing. A finite element analysis was also conducted to assess the mechanical environment over the course of bone healing. The quantitative data from the experimental test and finite element analysis was used in development of a computational model to simulate the bone healing process from the initial healing phase to the end.
As a clinical application of the bone healing simulation, a human tibial stress fracture was investigated through computational modeling. We hypothesized that there is a range of stress fracture depth and opening angle, where the stress fracture can heal by cession of excessive loading and resting alone; whereas surgical fixation would be required for higher values of stress fracture depths and opening angles. Therefore, different geometries of tibial stress fracture, including stress fracture depth, and opening angle were simulated. The goal was to determine the range of stress fracture depths and opening angles which stress fractures are capable of healing without any surgical intervention.
Computational simulations and experimental studies were performed in this study in order to promote modeling of bone healing simulation by considering the initial phase of healing and implement computational simulations capability in clinical applications. There is still a great potential in the field of bone healing simulation and further experimental and computational studies can be conducted to elevate its application in clinical problems.