Tunable Blood Shunt for Neonates With Complex Congenital Heart Defects

Ellen Garven; Christopher B Rodell; Kristen Shema; Krianthan Govender; Samantha E Cassel; Bryan Ferrick; Gabriella Kupsho; Ethan Kung; Kara L Spiller; Randy Stevens; Amy L Throckmorton

doi:10.3389/fbioe.2021.734310

Tunable Blood Shunt for Neonates With Complex Congenital Heart Defects

Front Bioeng Biotechnol. 2022 Jan 13:9:734310. doi: 10.3389/fbioe.2021.734310. eCollection 2021.

Authors

Ellen Garven¹, Christopher B Rodell², Kristen Shema^{1

3}, Krianthan Govender^{1

3}, Samantha E Cassel^{1

3}, Bryan Ferrick^{1

3}, Gabriella Kupsho¹, Ethan Kung⁴, Kara L Spiller³, Randy Stevens^{5

6}, Amy L Throckmorton¹

Affiliations

¹ BioCirc Research Laboratory, School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, United States.
² Tissue Instructive Materials Laboratory, School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, United States.
³ Biomaterials and Regenerative Medicine Laboratory, School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, United States.
⁴ Department of Mechanical Engineering and Bioengineering, Clemson University, Clemson, SC, United States.
⁵ Pediatrics, College of Medicine, Drexel University, Philadelphia, PA, United States.
⁶ Heart Center for Children, St. Christopher's Hospital for Children, Philadelphia, PA, United States.

Abstract

Despite advancements in procedures and patient care, mortality rates for neonatal recipients of the Norwood procedure, a palliation for single ventricle congenital malformations, remain high due to the use of a fixed-diameter blood shunt. In this study, a new geometrically tunable blood shunt was investigated to address limitations of the current treatment paradigm (e.g., Modified Blalock-Taussig Shunt) by allowing for controlled modulation of blood flow through the shunt to accommodate physiological changes due to the patient's growth. First, mathematical and computational cardiovascular models were established to investigate the hemodynamic requirements of growing neonatal patients with shunts and to inform design criteria for shunt diameter changes. Then, two stages of prototyping were performed to design, build and test responsive hydrogel systems that facilitate tuning of the shunt diameter by adjusting the hydrogel's degree of crosslinking. We examined two mechanisms to drive crosslinking: infusion of chemical crosslinking agents and near-UV photoinitiation. The growth model showed that 15-18% increases in shunt diameter were required to accommodate growing patients' increasing blood flow; similarly, the computational models demonstrated that blood flow magnitudes were in agreement with previous reports. These target levels of diameter increases were achieved experimentally with model hydrogel systems. We also verified that the photocrosslinkable hydrogel, composed of methacrylated dextran, was contact-nonhemolytic. These results demonstrate proof-of-concept feasibility and reflect the first steps in the development of this novel blood shunt. A tunable shunt design offers a new methodology to rebalance blood flow in this vulnerable patient population during growth and development.

Keywords: biomaterials; blood flow; computational fluid dynamics; congenital heart defects; hydrogels; pediatrics; shunt; single ventricle physiology.