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Advancing Toward Widely Available Tissue Engineered Vascular Grafts

Tissue engineered vascular grafts (TEVGs) offer many benefits over traditional synthetic materials for the Fontan conduit for children born with a single ventricle heart defect. But TEVGs are not an option for children with complex anatomies.

Christopher Breuer, MD, and Tosiharu Shinoka, MD, PhD, and their team of tissue engineers and imaging and design specialists at Nationwide Children’s Hospital were inspired by just such a patient excluded from their clinical trial of TEVG for use in Fontan patients.

They started a project to test the feasibility of using 3D printing to create a custom graft with a nonconstant diameter, greater length and a doubly meandering compound curve. Additionally, they wanted to see if they could do it without the labor-intensive, clean room-dependent seeding process, instead of using a closed disposable filtration/elution system.

“To take advantage of patient-specific modeling and customized regenerative implants to yield an optimized patient-specific TEVG is a natural extension of the progress in both fields,” says Dr. Breuer, director of the Center for Regenerative Medicine in The Research Institute at Nationwide Children’s.

The team used computer aided drafting (CAD) and the patient’s reconstructed cardiac magnetic resonance imaging to design a custom scaffold and seeding device. The scaffolds were co-electrospun from polyglycolic acid and L-lactide-co--caprolactone onto custom 3D printed mandrels.

The researchers also utilized CAD to recapitulate a previously proposed closed seeding apparatus, which was then 3D-printed from polylactide using a fused deposition modeler and sterilized with ethylene oxide gas. The seeding chamber held the volume of the scaffold, mandrel and 120 mL of enriched bone marrow mononuclear cells (BM-MNCs) used for seeding. In testing, the 3D-printed seeding apparatus performed equivalently to traditional open seeding.

“Notably, the concentration of BM-MNCs in this scenario was a fourfold higher dose than the current clinical protocol. Our work to date shows that increasing the number of cells seeded improves the quality of the graft,” says Cameron Best, a PhD student in the Center for Regenerative Medicine and lead study author.

The researchers suggest incorporating fluid dynamic computational modeling and other predictive techniques to model the optimal graft geometry across scales.

Best C, Strouse R, Hor K, Pepper V, Tipton A, Kelly J, Shinoka T, Breuer C. Toward a patient-specific tissue engineered vascular graft. Journal of Tissue Engineering. 2018;9:1-9.

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