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.We thank Marvin Estrada for animal care support and Tammy Rayner, Ruth Weiss, and Garry Detzler for technical assistance during MR scanning