Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth

Plain language summarySurgery to correct defects in the heart that are present at birth sometimes requires the use of artificial blood vessels called vascular grafts. Tissue-engineered vascular grafts (TEVGs) are scaffolds seeded with cells that can develop into functional blood vessels over time. We conducted a series of laboratory and computer-based experiments to investigate how TEVGs develop into functional blood vessels, and demonstrated two phases of changes to the TEVG after implantation: an early phase driven by inflammation, and a later phase driven by the mechanical properties of the tissue. At later time points, the resulting blood vessels demonstrated the ability to grow and respond to blood flow in similar ways to the body's own blood vessels. These results provide insight into the processes by which TEVGs become functional blood vessels, with implications for future clinical use of this technology. BackgroundTissue-engineered vascular grafts (TEVGs) have the potential to advance the surgical management of infants and children requiring congenital heart surgery by creating functional vascular conduits with growth capacity.MethodsHerein, we used an integrative computational-experimental approach to elucidate the natural history of neovessel formation in a large animal preclinical model; combining an in vitro accelerated degradation study with mechanical testing, large animal implantation studies with in vivo imaging and histology, and data-informed computational growth and remodeling models.ResultsOur findings demonstrate that the structural integrity of the polymeric scaffold is lost over the first 26 weeks in vivo, while polymeric fragments persist for up to 52 weeks. Our models predict that early neotissue accumulation is driven primarily by inflammatory processes in response to the implanted polymeric scaffold, but that turnover becomes progressively mechano-mediated as the scaffold degrades. Using a lamb model, we confirm that early neotissue formation results primarily from the foreign body reaction induced by the scaffold, resulting in an early period of dynamic remodeling characterized by transient TEVG narrowing. As the scaffold degrades, mechano-mediated neotissue remodeling becomes dominant around 26 weeks. After the scaffold degrades completely, the resulting neovessel undergoes growth and remodeling that mimicks native vessel behavior, including biological growth capacity, further supported by fluid-structure interaction simulations providing detailed hemodynamic and wall stress information.ConclusionsThese findings provide insights into TEVG remodeling, and have important implications for clinical use and future development of TEVGs for children with congenital heart disease. Blum et al. combine computational and experimental methods to study the long-term development of tissue engineered vascular grafts in a lamb model. The authors demonstrate that the grafts undergo growth and remodeling, evolving to mimic the characteristics and function of a native blood vessel.