Computational Model-Driven Design of Tissue Engineered Vascular Grafts

Doctor's Name: 
Ramak Khosravi
Yale University

Collaboratively awarded through the CHF and AHA Congenital Heart Defect Research Awards

(Total Grant Amount $51,900; CHF Portion: $28,026)

Our research is aimed at creating a new replacement conduit for children and adults suffering from cardiovascular disease and requiring surgical intervention. Most of these patients do not have suitable arteries and veins to replace their diseased vessels. Currently used grafts are made of materials that do not degrade, lack growth potential, and are prone to complications. To overcome this, we are engineering arterial grafts from biodegradable polymers, with reduced costs and off-the-shelf availability, which will over time be replaced by the patient’s own cells. We can improve graft design using computer simulations and long-term studies in a mouse model to identify the optimal design for patients needing grafts for bypass procedures, hemodialysis, or repair of congenital heart defects.

There has yet to be a formal attempt to optimize the design of polymeric scaffolds such that they have biomechanical properties closest to native arteries. We will begin by surgically implanting multiple scaffolds with different design features, and evaluate their performance in our mouse model. We will then evaluate which design features are critical for controlling the inflammatory response to the polymer, and identify the key cells and signaling molecules involved. Finally, we will use the data to develop and inform a computational model of arterial graft development that uniquely combines biochemistry and mechanics. Once validated, the model can be used to perform many time- and cost-efficient simulations and identify scaffold properties predicted to give optimal long-term outcomes.

Successful completion of this research will not only establish a new computational-experimental approach for arterial tissue engineering, but will also result in a significantly improved graft for use in the arterial circulation. This is critical for children and adults requiring surgical interventions for cardiovascular disease, which in the U.S alone is over 600 000 patients annually. Our grafts will be comprised entirely of the patient’s own cells, available off-the-shelf, and greatly reduced in cost. They can be fabricated with properties that ensure patient specificity, such as growth capacity in children and compliance matching and mechanical strength in adult patients, and computational predictions may also guide appropriate pharmacological therapies following graft implantation.

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