An Agent-Based Model for the Investigation of Neovascularization Within Porous Scaffolds

Abstract

The ability to control blood vessel assembly in polymer scaffolds is important for clinical success in tissue engineering. A mathematical and computational representation of the relationship between scaffold properties and neovascularization may provide a better understanding of the fundamental process itself and help guide the design of new therapeutic approaches. This article proposes a multilayered, multiagent framework to model sprouting angiogenesis in porous scaffolds and examines the impact of pore structure on vessel invasion and network structure. We have defined the speed of vessel sprouting in the agent-based model based on in vivo results in the absence of a polymer scaffold. A number of cases were run to investigate the effect of scaffold pore size on angiogenesis. The simulation results indicate that the rate of scaffold vascularization increases with pore size. Pores of larger size (160-270 μm) support rapid and extensive angiogenesis throughout the scaffold. Model predictions were compared to experimental results of vascularization in porous poly(ethylene glycol) hydrogels to validate the results. This model can be used to provide insight into optimal scaffold properties that support vascularization of engineered tissues.

Three-Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size

“…152,153 Artel et al showed that larger pore sizes of approximately 160 to 270 mm facilitated angiogenesis throughout scaffold by using multilayered agent-based model simulation. 154 This model was used to investigate the relationship between angiogenesis and scaffold properties. The materials were assumed to be slowly degrading or nondegradable, such that the pore sizes remained constant.…”

Evaluating Changes in Structure and Cytotoxicity DuringIn VitroDegradation of Three-Dimensional Printed Scaffolds

“…21,22 In addition, previous studies have shown that for scaffolds with pores larger than 270 mm, it is as if there is no scaffold to hinder the vascularization process. 23 Studies have also shown that interconnected pores above 300 mm may improve nutrient flow. 24 As this scaffold is expected to function as a delivery method for bioactive materials for the bone tissue applications, it is anticipated that the cells that will interact with the pores would primarily be mesenchymal stem cells or osteoblasts.…”

Periodontal repair following implantation of beta-tricalcium phosphate with different pore structures in class III furcation defects in dogs

“…Several studies have reported that porous structures enhance bone formation in bone defects [12][13][14][15][16] . Furthermore, it has been shown that pore size has an effect on vascularization 17,18) . Pore sizes greater than 140 μm induced earlier vessel formation in biomaterials when compared with pore sizes smaller than 140 μm or dense particles 17) .…”

“…Pore sizes greater than 140 μm induced earlier vessel formation in biomaterials when compared with pore sizes smaller than 140 μm or dense particles 17) . Also, new vessels arising from the residual tissue can increase the number of vessels in macropores, whereas only a few vessels in a macropore could extend into the adjacent macropore through the small connecting area with pore sizes smaller than 140 μm 18) . Vascularization in the defect ensures an adequate supply of nutrients and delivery of cells and growth factors that support the formation of osseous tissue 19) .…”