Session: IMECE Undergraduate Research and Design Exposition

Paper Number: 120633

120633 - Continuum-Based Particle Model of Bone Morphogenesis Predicts Changes in Tissue Shape and Structure Due to Secondary Ossification 

Bone morphogenesis is crucial for determining each bone’s shape and structure for its proper function. During morphogenesis, growing cartilage is replaced by bone in the process of endochondral ossification. This process involves chondrocyte cell proliferation, growth, and differentiation which are tightly regulated by biochemical and mechanical signals. It can be difficult to understand the effects of a specific factor on overall bone shape using experimental methods, so computational approaches are useful to study the role of biochemical and mechanical factors. In this study, we aim to develop a model of bone morphogenesis that accounts for heterogenous cell activities and incorporates both biochemical and mechanical factors to predict changes in bone shape. We specifically focus on secondary ossification and seek to understand how formation of the secondary ossification center (SOC) affects the overall shape and structure of the tissue.

 

In this study we use a continuum-based particle model. Previous computational approaches have used finite element methods (FEM) to simulate bone growth and ossification. However, FEM is unable to capture spatiotemporally heterogenous cell activities at a single-cell level. To capture the distinct proliferation, hypertrophy, and differentiation of different cell types, we use a continuum-based particle model instead. Our model is based on the material point method, where a physical body is represented by discrete material points [1]. We consider a material point as a single cell and its surrounding matrix, and we model each material point with distinct cell activities and mechanical properties based on its cell type. We also incorporate two important biochemical regulators Indiah hedgehog (Ihh) and parathyroid hormone-related protein (PThrP) to regulate proliferation and differentiation. Our model is able to simulate development from the onset of primary ossification through secondary ossification.

 

To predict the effect of SOC development on overall tissue shape and structure, we conducted simulations replicating metatarsal bone development. In metatarsal bones, secondary ossification only occurs at one end. Therefore, by simulating bone growth with and without SOC formation, we replicate the distinct proximal and distal ends of the metatarsal bone. In simulations with SOC formation, the primary ossification center (POC) expands longitudinally, and the SOC expands radially, with the growth plate maintained in between the two centers. In simulations without SOC formation, the POC progresses until it nears the end of the bone. These simulation results show qualitative agreement with experimental images of metatarsal development [2]. Additionally, the simulations predict differences in cell number, overall bone dimensions, and strain energy density between the two cases. In simulations with formation of the SOC, we observe a wider epiphysis, increased number of cells, and higher strain energy density in the periarticular region and resting zone.

 

In summary, our model incorporates both biochemical and mechanical factors to simulate bone morphogenesis through secondary ossification and can predict changes in bone shape and structure. Further studies could validate the model against experimental data, allowing for accurate quantitative predictions. The ability of the continuum-based particle method to predict changes in tissue properties in response to heterogenous cell activity makes it a powerful tool for investigating morphogenesis. In the future, our model could also be used to explore the effects of position and timing of SOC initiation on overall bone shape, and it could be extended to investigate the role of external forces in morphogenesis as well.

 

1.      Yokoyama, Yuka, Kameo, Yoshitaka, and Adachi, Taiji. “Development of continuum-based particle models of cell growth and proliferation for simulating tissue morphogenesis.” Journal of the Mechanical Behavior of Biomedical Materials Vol. 142 (2023). DOI 10.1016/j.jmbbm.2023.105828.

 

2.      Reno, Philip L., Mcburney, Denis L., Lovejoy, C. Owen, and Horton, Water E., Jr. “Ossification of the mouse metatarsal: Differentiation and proliferation in the presence/absence of a defined growth plate.” The Anatomical Record. Vol. 288A (2006): pp. 104-118. DOI 10.1002/ar.a.2026

Presenting Author: Jorik Stoop Georgia Institute of Technology

Presenting Author Biography: I am a fourth year Biomedical Engineering student at Georgia Tech interested in computational modeling, biomechanics, and mechanobiology.

Authors:

Jorik Stoop Georgia Institute of Technology
Yuka Yokoyama Kyoto University
Taiji Adachi Kyoto University