Sanchita Bhat 

BioE Ph.D. Thesis Defense  

Time and Date: 1:30 PM, Monday, November 13th, 2023  

Location:   IBB Rm 2316 

https://gatech.zoom.us/j/95234897937

Advisor:   

Lakshmi Prasad Dasi, Ph.D. (Georgia Institute of Technology)  

Committee:  

Ajit P. Yoganathan, Ph.D. (Georgia Institute of Technology)  

Christopher Breuer, M.D. (Nationwide Children’s Hospital)  

Rudolph Gleason, Ph.D. (Georgia Institute of Technology)  

Scott Hollister, Ph.D. (Georgia Institute of Technology)  

Development and Biomechanical Assessment of Heart Valve Replacements Designed for In Utero Deployment 

      Congenital heart diseases (CHDs) account for nearly one third of all congenital defects. Patients born with complex congenital cardiac anomalies often require heart valve replacements in their lifetimes. Prenatally, attempts have been made to restore biventricular healthy anatomy in utero by balloon valvuloplasty. A lot of patients that undergo this procedure develop re-atresia or re-stenosis, requiring valve replacements. There has been an investigation into providing a permanent solution to heart valve replacements in children using tissue engineering. 'Neo-tissue' develops using the patient’s own cells, and therefore eradicates the susceptibility of severe rejection possessing the ability to grow, repair and remodel. Tissue engineering can be used as a viable tool in the fetal population due to the high regenerative capacity. This study developed a fetal transcatheter pulmonary valve replacement. The overall hypothesis is that improved understanding of the biomechanics of manufacturing and testing of biodegradable materials can help engineer fetal sized tissue engineered heart valves (TEHVs) and guide future transcatheter device interventions. 

      Specific Aim 1 shed light on the stress distributions and stent characteristics of candidate stent designs simulated with four candidate materials (metal and polymeric).  Results showed differences in stress distributions and stent performance metrics (dog boning, foreshortening and recoil) in the three designs. Both metals performed favorably, although polymer performance (due to high elastic modulus) was better suited to current designs. It was also shown that design had a great effect on distribution of high stresses and composite materials need to be explored in the future to combine the advantages of both metals and polymers. Specific Aim 2 developed and tested alternative sutureless valve assembly techniques that can overcome potential premature failure of valves and benchtop tested patterns of leaflet degradation. Results showed that changing the material density in the valve assembly can help control degradation and performance of the valve in vivo. Specific Aim 3 looked at fetal valve hemodynamic performance and downstream fluid profiles in a pulse duplicator and durability in an AWT. Results showed that although performance values differ between prototypes, all performed well individually and durability in a non-degrading medium was high, indicating the possible longevity of valve in vivo. 

      The development of such a TEHV will eliminate the need for repeat interventions and serve as a permanent alternative. Given the few durable options for pediatric patients, this study will improve the feasibility of developing such a device right from the manufacturing to the testing stage. This critical integration of heart valve and tissue engineering may be the first step to the solution that is needed to reverse ventricular hypoplasia and eliminate single ventricle anomalies.