title: Agent-based modeling of porous scaffold degradation and vascularization: Optimal scaffold design based on architecture and degradation dynamics.
abstract: A multi-layer agent-based model (ABM) of biomaterial scaffold vascularization is extended to consider the effects of scaffold degradation kinetics on blood vessel formation. A degradation model describing the bulk disintegration of porous hydrogels is incorporated into the ABM. The combined degradation-angiogenesis model is used to investigate growing blood vessel networks in the presence of a degradable scaffold structure. Simulation results indicate that higher porosity, larger mean pore size, and rapid degradation allow faster vascularization when not considering the structural support of the scaffold. However, premature loss of structural support results in failure for the material. A strategy using multi-layer scaffold with different degradation rates in each layer was investigated as a way to address this issue. Vascularization was improved with the multi-layered scaffold model compared to the single-layer model. The ABM developed provides insight into the characteristics that influence the selection of optimal geometric parameters and degradation behavior of scaffolds, and enables easy refinement of the model as new knowledge about the underlying biological phenomena becomes available.
  
  
  CONCLUSIONS
  This paper proposes a multi-layer agent-based model (ABM) of biomaterial scaffold vascularization integrated with a structural-kinetic model describing bulk degradation of porous hydrogels to consider the effects of scaffold degradation kinetics on blood vessel formation. This enables the assessment of scaffold characteristics and in particular the disintegration characteristics of the scaffold on angiogenesis. Simulation results indicate that higher porosity, larger mean pore size, and rapid degradation allow faster vascularization when not considering the structural support of the scaffold. However, premature loss of structural support by scaffold disintegration results in failure of the material and disruption of angiogenesis. A strategy using multi-layer scaffold with different degradation rates in each layer was investigated as away to address this issue. Vascularization was improved with the multi-layered scaffold model compared to the single-layer model. The ABM developed provides insight into the characteristics that influence the selection of optimal geometric and degradation characteristics of tissue engineering scaffolds.
authors.affiliation: Department of Chemical and Biological Engineering, Illinois Institute of Technology, 10 W 33rd St, Suite 127, Chicago, IL 60616, USA.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Mehdizadeh
authors.affiliation: Department of Chemical and Biological Engineering, Illinois Institute of Technology, 10 W 33rd St, Suite 127, Chicago, IL 60616, USA.
authors.forename: Elif S
authors.initials: ES
authors.lastname: Bayrak
authors.affiliation: Department of Chemical and Biological Engineering, Illinois Institute of Technology, 10 W 33rd St, Suite 127, Chicago, IL 60616, USA.
authors.forename: Chenlin
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, Illinois Institute of Technology, Suite 314, 3255 S Dearborn St, Chicago, IL 60616, USA.
authors.forename: Sami I
authors.initials: SI
authors.lastname: Somo
authors.affiliation: Department of Biomedical Engineering, Illinois Institute of Technology, Suite 314, 3255 S Dearborn St, Chicago, IL 60616, USA.
authors.forename: Banu
authors.initials: B
authors.lastname: Akar
authors.affiliation: Department of Biomedical Engineering, Illinois Institute of Technology, Suite 314, 3255 S Dearborn St, Chicago, IL 60616, USA; Research Service, Hines Veterans Administration Hospital, Hines, IL, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Brey
authors.affiliation: Department of Chemical and Biological Engineering, Illinois Institute of Technology, 10 W 33rd St, Suite 127, Chicago, IL 60616, USA; Department of Biomedical Engineering, Illinois Institute of Technology, Suite 314, 3255 S Dearborn St, Chicago, IL 60616, USA. Electronic address: cinar@iit.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Cinar
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D021522:Bioartificial Organs; D001672:Biocompatible Materials / Q000737:chemistry; D001807:Blood Vessel Prosthesis; D001808:Blood Vessels / Q000166:cytology / Q000254:growth & development*; D003198:Computer Simulation; D017076:Computer-Aided Design; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D019544:Equipment Failure Analysis; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007700:Kinetics; D008955:Models, Cardiovascular; D018919:Neovascularization, Physiologic / Q000502:physiology*; D016062:Porosity; D011474:Prosthesis Design; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels
keywords: Agent-based modeling; Multi-layer scaffold model; Scaffold degradation model; Vascularization