(333e) Agent-Based Simulation of Vascularized Bone Formation in Degradable Scaffolds

The success of engineered bone tissue growth in biomaterial scaffolds is determined by the rich vascular supply and high mineralization. Blood vessel formation through angiogenesis from host tissue is the common mechanism for scaffold vascularization. Bone growth can be induced by either external growth factor supply or ceramic incorporation to stimulate cell differentiation and growth. Calcium phosphates, such as tricalcium phosphate (TCP), and hydroxyapatite (HA) are widely used materials due to their high biocompatibility and osteoinductivity. Interactions between blood vessel formation, bone cell growth and modified biomaterial structure are often difficult to study with experimentation alone. Computational models are powerful tools to test different hypothesis and strategies to explore promising alternatives in an organized manner. Due to the complexity and heterogeneity involved in the biomaterial environment, conventional mechanistic models are sometimes inadequate to describe the underlying biological processes. Agent-based models (ABM) represent the individual decision makers in the system such as cells, organelles, genes, or molecules by software agents while allowing an easy integration with continuous models for more realistic environment description. We have previously developed an ABM to study angiogenesis (Mehdizadeh et al., 2013) and osteogenesis (Bayrak et al., 2014) in porous, growth-factor-loaded biomaterials. The current work extends and modifies the model to investigate bone tissue regeneration and study the effects of HA and TCP incorporation to degradable, porous, biomaterial structure. The model showed bone regeneration can be induced using HA- and TCP-loaded scaffolds and suggested the optimum ratio between these materials.

References

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