Agent-based modeling of porous scaffold degradation and vascularization: Optimal scaffold design based on architecture and degradation dynamics

• Published in: Acta biomaterialia Vol. 27; pp. 167 - 178
• Main Authors: Mehdizadeh, Hamidreza, Bayrak, Elif S., Lu, Chenlin, Somo, Sami I., Akar, Banu, Brey, Eric M., Cinar, Ali
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2015
• Subjects: Absorbable Implants; Agent-based modeling; Animals; Bioartificial Organs; Biocompatible Materials - chemistry; Blood Vessel Prosthesis; Blood vessels; Blood Vessels - cytology; Blood Vessels - growth & development; Computer Simulation; Computer-Aided Design; Degradation; Disintegration; Endothelial Cells - cytology; Endothelial Cells - physiology; Equipment Failure Analysis; Humans; Hydrogels - chemistry; Kinetics; Mathematical models; Models, Cardiovascular; Multi-layer scaffold model; Multilayers; Neovascularization, Physiologic - physiology; Porosity; Prosthesis Design; Scaffold degradation model; Scaffolds; Supports; Tissue Scaffolds; Vascularization; Scaffold degradation model; Agent-based modeling; Multi-layer scaffold model; Vascularization
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2015.09.011

3D rendering of a degradable multi-layer scaffold vascularization over time. The scaffold is divided into three regions with different degradation rates: layer 1 (dark gray), layer 2 (gray), and layer 3 (white) from bottom to top. The bottom layer (layer 1) has the faster degradation rate. There is a remarkable improvement in vascularization with the multi-layered scaffold model that continues to provide mechanical support in its upper layers when the lower layers have degraded compared to a single-layer model. [Display omitted]
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.
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 angiognesis. 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.