(376b) Multi-Agent Model of Vascularized Bone Tissue Growth within Porous Biomaterials

Engineering bone tissue from stem cell seeded biomaterials has been recognized as a promising technique on the repair of bone tissue defects above the critical size.  Rapid and stable vascularization of scaffolds is required to supply nutrients and oxygen that stem cells need to survive as well as to go through osteogenic differentiation. The process of bone formation from stem cells and simultaneous vascularization involve the combination of many complex interacting factors and provide challenges to tissue engineers. Experiments alone are not sufficient to study the effects and interactions of various components involved in tissue formation such as biodegradable scaffolds, signaling molecules and different types of cells. A computational model that can realistically simulate the behavior of such systems over time would be beneficial for many different theoretical and practical purposes. These purposes include rapid testing of alternative hypotheses, better understanding the mechanisms involved, estimation of the important variables of the system and prediction of their effects on system level behaviors. A simulation based on the computational model will provide a tool for rapidly screening alternatives, determining the most promising experimental search space and investigating ways of intervening in such systems for functional tissue formation.

Agent-based modeling techniques can be used to study complex systems with many interacting elements. The central idea in agent-based models (ABM) is to define agents that represent the building blocks of a system and to develop rules that regulate their interactions. The rules originate from the vast qualitative and quantitative knowledge gained through many years of studying the individual components of these biological systems. Agent-based systems are naturally suitable for modeling biological systems as they are comprised of individual constituents like cells that interact with each other to form macro-scale bodies like tissue.

In this study, a multi-layer ABM is presented to simulate tissue growth and vascular network formation within porous biodegradable scaffold.  In our model, one layer describes the event occurring within the scaffold, the second layer describes the angiogenesis, focusing the individual behavior of endothelial cells, and finally the third layer simulates the behavior of stem cells and their osteogenic differentiation. This computational framework, coupling two different interacting cell types, is used to investigate cellular response to structural changes of biomaterials and different strategies to maximize vascularization and bone regeneration.