Optimizing scaffold architecture for perfect osteointegration depends on good understanding of bone ingrowth in the porous space of implants. This study developed an immunoregulatory agent-based model to discover the osteoinduction mechanism in porous scaffolds. Immunoreaction, macrophage polarization, and the corresponding growth factors were combined in the model, and all played critical roles in recruiting osteogenic cells that migrated into the scaffolds. Angiogenesis was also considered in this model. The bone ingrowth predicted by the model coincides with results from published in vivo experiments. Simulation results suggested that the pore architecture affected the diffusion process of chemotactic factors in the scaffolds, subsequently influencing the complex reactions of diverse cells and the osteoinduction location. In flexural pore spaces, bone formation spread from the periphery into the center of scaffolds due to larger M2 phenotype macrophage populations colonizing boundary regions and the distribution of corresponding growth factors concentration. In straight channels, osteogenic cells migrated further inward and osteoinduction initiated in deeper position as a result of the deeper distribution of osteogenic cytokines concentration field.
Keywords: Immune regulation; Multi-scale modeling; Osteoinduction; Porous scaffold.
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