Monitoring angiogenesis in soft-tissue engineered constructs for calvarium bone regeneration: an in vivo longitudinal DCE-MRI study.

Tissue engineering is a promising technique for bone repair and can overcome the major drawbacks of conventional autogenous bone grafting. In this in vivo longitudinal study, we proposed a new tissue-engineering paradigm: inserting a biological soft-tissue construct within the bone defect to enhance angiogenesis for improved bone regeneration. The construct acts as a resorbable scaffold to support desired angiogenesis and cellular activity and as a vector of vascular endothelial growth factor, known to promote both vessel and bone growth. Dynamic contrast- enhanced magnetic resonance imaging was performed to investigate and characterize angiogenesis necessary for bone formation following the proposed paradigm of inserting a VEGF-impregnated tissue-engineered construct within the critical-sized calvarial defect in the membranous parietal bone of the rabbit. Results show that a model-free quantitative approach, the normalized initial area under the curve metric, provides sensitive and reproducible measures of vascularity that is consistent with known temporal evolution of angiogenesis during bone regeneration.