Agent-based modeling of angiogenesis within degradable biomaterial scaffolds

The ability to promote and control blood vessel assembly in polymer scaffolds is important for clinical success in tissue engineering. Mathematical and computational representation of the relationship between scaffold properties and neovascularization facilitates studying the fundamental processes involved in vascularization of biomaterials and provides more profound understanding of the critical factors that affect this process. This understanding is critical for the design of new therapeutic approaches that could bridge the existing gap between current experimental techniques and the state of the art practical tissue regeneration approaches.;A multi-agent framework is developed to model the process of sprouting angiogenesis within porous biodegradable tissue engineering scaffolds. A rule base governs the behavior of individual agents. Two-dimensional and three-dimensional scaffold models with well-defined homogeneous and heterogeneous pore architectures are designed and simulated to investigate the impact of various scaffold design parameters such as pore size, pore size distribution, interconnectivity, and porosity, as well as the degradation behavior of the scaffolds, on vessel invasion and capillary network structure. Model parameters are adjusted based on independent results of in vivo vascularization of fibrin gels in the absence of a polymer scaffold. The effects of various characteristics of scaffold degradation are also investigated. The simulation results are compared with available experimental results of scaffold vascularization performed in our group and with relevant published literature data to validate the developed model. These results indicate that in general the rate of vascularization increases with larger pore size and higher interconnectivity and porosity scaffolds.;The agent-based model can be used to provide insight into optimal scaffold properties that support vascularization of engineered tissues. The modeling framework developed provides a novel interface for convenient integration of new knowledge to the current computational models, making it possible to gradually increase the level of complexity and accuracy of the models as our knowledge about the underlying biological system advances. The simulation results help us better understand the complex interactions between the growing blood vessel network and a degrading scaffold structure, and identify the optimal combinations of geometric and degradation characteristics of tissue engineering scaffolds that support scaffold vascularization.