(229v) Multi-Layer Agent-Based Modeling of Vascularized Bone Regeneration within a Porous Biomaterial Scaffold with Growth Factor Gradient

The success of engineered bone tissue regeneration requires the synergistic combination of biomaterial scaffolds, growth factors, and osteogenic cells. Biomaterial scaffolds serve as a temporary matrix for cell proliferation and extracellular matrix deposition, as well as a template for vascularization. The formation of a sufficient and proper vascular network is critical for the survival of the regenerated tissues. Exogenous growth factors released from the scaffold, including osteogenic growth factors (e,g, bone morphogenetic protein 2, BMP2) and angiogenic growth factors (e.g. vascular endothelial growth factor, VEGF), are often required to promote the osteoblastic differentiation of stem cells and angiogenesis, respectively. The interactions between blood vessel formation, growth factor release, bone cell growth, and scaffold structure properties are often difficult to investigate systematically with experimentation alone. Computational models provide powerful tools to simulate the process of bone tissue regeneration within biomaterial scaffolds, and capable to test hypothesis and strategies to enhance bone tissue regeneration in an organized manner. Due to the complexity and heterogeneity of the whole process of bone tissue regeneration, conventional empirical and mechanistic models are sometimes inadequate to describe the underlying biological process. Agent-based modeling (ABM) is well suited for modeling multi-cellular biomedical systems where different type of cells, molecules, and organelles can be represented as autonomous, interacting software agents while allowing an easy integration with continuous models for more realistic environment description.

We have previously developed an ABM to investigate angiogenesis (Mehdizadeh et al., 2013) and osteogenesis (Bayrak et al., 2014) in a porous, degradable biomaterial scaffold. In addition, a biomaterial system that creates gradients of growth factors within the porous scaffold was developed to accelerate scaffold vascularization (Akar et al., 2015). The current work extends and modifies the ABM to simulate the interaction between stem cells and growth factors. Both endogenous and exogenous growth factor release are considered to investigate the effects on bone tissue regeneration. The multi-layer ABM is utilized to investigate optimum growth factor gradient properties and scaffold geometrical structure to form clinical size vascularized bone tissue.

Reference:

Bayrak, E. S., Mehdizadeh, H., Akar, B., Somo, S. I., Brey, E. M. & Cinar, A. Agent-Based Modeling Of Osteogenic Differentiation Of Mesenchymal Stem Cells In Porous Biomaterials. Engineering In Medicine And Biology Society (EMBC), 2014 36th Annual International Conference Of The IEEE, 2014. IEEE, 2924-2927.

Mehdizadeh, H., Somo, S., Bayrak, E. S., Brey, E. M. & Cinar, A. 2013. Three-Dimensional Modeling of Angiogenesis In Porous Biomaterial Scaffolds. Biomaterials, 34, 2875-2887.

Akar, B., Jiang, B., Somo, S.I., Appel, A.A., Larson, J.C., Tichauer, K.M. and Brey, E.M., 2015. Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation. Biomaterials, 72, pp.61-73.