Dynamic contrast-enhanced MRI to quantify VEGF-enhanced tissue-engineered bladder graft neovascularization: pilot...

Area of Science:

• Regenerative Medicine
• Biomaterials Science
• Medical Imaging

Background:

• Tissue engineered organs require immediate vascularization for survival and function.
• Current neovascularization assessment methods involve invasive animal sacrifice and graft harvesting.
• Developing non-invasive assessment techniques is crucial for advancing tissue engineering.

Purpose of the Study:

• To evaluate if vascular-derived endothelial growth factor (VEGF) enhances neovascularization in engineered urinary bladder constructs.
• To determine the feasibility of using dynamic contrast-enhanced MRI (DCE-MRI) for non-invasive assessment of neovascularization.
• To correlate MRI findings with quantitative measures of microvasculature.

Main Methods:

• Rabbit bladder acellular matrix hybridized with hyaluronic acid (ACM-HA) was fortified with varying concentrations of VEGF (0, 10, 20 ng/g).
• Constructs were grafted onto rabbit bladders, and DCE-MRI was performed at 1, 2, and 3 weeks post-implantation.
• Microvascular area (MVA) was quantified via CD31 staining and optical sectioning; histological analysis assessed cellularity and fibrosis.

Main Results:

• A significant increase in mean microvascular area (MVA) was observed between the 10 ng and 20 ng VEGF groups (P=0.014).
• Gadolinium uptake on DCE-MRI positively correlated with MVA (r=0.71), indicating MRI's ability to reflect vascularization.
• The highest VEGF concentration group showed increased stromal cellularity and reduced fibrosis at 3 weeks.

Conclusions:

• VEGF fortification of ACM-HA constructs significantly improves neovascularization in engineered bladder tissue.
• DCE-MRI is a feasible non-invasive method for assessing angiogenesis in tissue-engineered constructs.
• This approach holds promise for monitoring graft development and optimizing tissue engineering strategies.