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Title

AGENT-BASED MODELING OF ANGIOGENESIS WITHIN DEGRADABLE BIOMATERIAL SCAFFOLDS

Creator

Mehdizadeh, Hamidreza

Date

2013, 2013-12

Description

The ability to promote and control blood vessel assembly in polymer scaffolds is important for clinical success in tissue engineering. Often,...
Show moreThe ability to promote and control blood vessel assembly in polymer scaffolds is important for clinical success in tissue engineering. Often, experimental studies are performed to investigate the role of scaffold architecture on vascularized tissue formation. However, experiments are expensive and time-consuming and synthesis protocols often do not allow for independent investigation of specific scaffold properties. 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. Computational models allow for rapid screening of potential material designs with control over scaffold properties that is difficult in laboratory settings. In this work, a multi-layered, multi-agent framework is developed to model the process of sprouting angiogenesis within porous biodegradable tissue engineering scaffolds. Software agents are designed to represent endothelial cells, interacting together and with their micro-environment, leading to formation of new blood vessels that perfuse the scaffold. A rule base, derived from the experimental findings reported in the literature, or observed by our collaborators, 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 2 the scaffolds, on vessel invasion and capillary network structure. Model parameters such as the speed of vessel sprouting or cell migration speed 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. Various scenarios are defined and simulation case studies are developed to investigate the effect of scaffold geometrical and structural properties on angiogenesis. 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. Pores of larger size (160-270 μm) support rapid and extensive angiogenesis, however vascularizing deeper parts of the scaffolds still remains a challenge that requires more complex scaffold designs. 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.
PH.D in Chemical Engineering, December 2013
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