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Agent-basedmodels (ABMs) provide a flexible multilayer platformfor incorporating various modeling techniques into a single hybridmodel for designing optimal biomaterial scaffolds for angiogenesisin tissue engineering applications. Scaffold geometrical variablesare considered as design variables. The growth-factor concentrationprofile is the only process variable considered in this study. Theproduct variables used to illustrate the combined effects of scaffolddesign variables and process variables on the outcome of angiogenesisinclude the density and depth of capillary invasion within the scaffold.The scaffold design process and the ABM developed to simulate angiogenesisare described in this article. The performance of the ABM and thevascularization of the polymer scaffolds are evaluated by simulationstudies. The effects of pore size, pore size distribution, and interconnectivityon the total blood vessel length, invasion depth, and total numberof sprouts formed during the vascularization process are reported.The integration of the simulation of angiogenesis with ABMs and scaffolddesign techniques provides an iterative process for designing optimalscaffold structures. Such an approach facilitates faster design ofoptimized scaffolds with significantly less cost and enables betterunderstanding of the mechanisms of angiogenesis of polymer scaffoldsfor tissue engineering applications. [ABSTRACT FROM AUTHOR]