Mechanical-chemical coupled modeling of bone regeneration within a biodegradable polymer scaffold loaded with VEGF

Repairing critical-size bone defects with engineered scaffolds remains a challenge in orthopedic practice. Insufficient vascularization is a major reason causing the failure of bone regeneration within scaffolds. Loading exogenous vascular endothelial growth factor (VEGF) in biodegradable polymer scaffolds and controlling its release rate can promote vascularization in scaffolds and accelerate bone regeneration during bone repair. In this study, we developed a 3D mechanical-chemical model of bone regeneration, which combines multiple mechanical-chemical factors including mechanical stimulation, scaffold degradation, VEGF release and transportation, vascularization and oxygen delivery. This model simulated the coupled dynamic mechanical-chemical environments during bone regeneration and scaffold degradation and predicted bone growth under different mechanical-chemical conditions. Moreover, the predictive power of the model was preliminarily validated by experimental data in literature. Based on the validated model, the effect of exogenous VEGF doses on bone regeneration and the optimal doses under different mechanical stimulations was investigated. The simulation results suggested that there was an optimal range of VEGF doses, which promoted the efficiency of bone regeneration, and an appropriate mechanical stimulation improved the effect of VEGF on bone regeneration. The present work may provide a useful platform for future design of bone scaffolds to regenerate functional bones.