Christopher Breuer, Co-Director, Pediatric Surgery / Tissue Engineering, Nationwide Children’s Hospital, “Cardiovascular Tissue Engineering”

Topic: Cardiovascular Tissue Engineering

Abstract: Development of a vascular conduit with growth capacity has the potential to advance the field of congenital heart surgery and improve outcomes for children born with severe cardiac anomalies. We recently completed the first FDA-approved clinical trial evaluating the use of tissue engineered vascular grafts (TEVGs) as a conduit connecting the inferior vena cava to the pulmonary artery in patients with single ventricle cardiac anomalies undergoing extracardiac Fontan operations. This study confirmed the TEVG’s growth capacity, but it also demonstrated a previously undescribed period of dynamic remodeling, resulting in stenosis approximately 6 months postoperatively in 75% of the grafts. All cases of stenosis were successfully managed with balloon angioplasty, but the trial was placed on hold due to the unexpectedly high incidence of stenosis. To better understand the process of stenosis and neotissue formation, we employed a computational model of growth and remodeling. The model predicted the observed early dynamic remodeling and stenosis experienced in our trial, but surprisingly, it also predicted a spontaneous reversal of the narrowing. We tested this prediction by implanting TEVGs as interposition grafts in an ovine model, which confirmed that TEVG stenosis spontaneously resolves and is typically a well-tolerated component of neovessel formation. TEVG stenosis appears to result from a sudden loss of stress shielding during scaffold degradation, highlighting the critical role of mechanical homeostasis in mediating neotissue formation. Overall, our computational-experimental study demonstrates that TEVGs transform into living vascular conduits with the ability to remodel and grow longitudinally. The resulting neovessels are similar in structure and function to the native vessels into which they are implanted.