Challenges in translating vascular tissue engineering to the pediatric clinic

Abstract

The development of tissue-engineered vascular grafts for use in cardiovascular surgery holds great promise for improving outcomes in pediatric patients with complex congenital cardiac anomalies. Currently used synthetic grafts have a number of shortcomings in this setting but a tissue engineering approach has emerged in the past decade as a way to address these limitations. The first clinical trial of this technology showed that it is safe and effective but the primary mode of graft failure is stenosis. A variety of murine and large animal models have been developed to study and improve tissue engineering approaches with the hope of translating this technology into routine clinical use, but challenges remain. The purpose of this report is to address the clinical problem and review recent advances in vascular tissue engineering for pediatric applications. A deeper understanding of the mechanisms of neovessel formation and stenosis will enable rational design of improved tissue-engineered vascular grafts.

Figure 1

Growth potential of TEVG in clinical trial. A. Magnetic resonance image (MRI) 9 months following implantation of EC TCPC graft. B. 3-D computed tomography angiogram (CTA) of graft one year after implantation. Red arrows indicate location of tissue-engineered vascular graft. (Adapted with permission from Shinoka (2008) [23]).

Figure 2

TEVG remodeling in a mouse model. A. Inflammation-mediated process of graft remodeling. Seeded BM-MNC attach to the scaffold and release cytokines. MCP-1 recruits host monocytes which infiltrate the scaffold and begin to direct neotissue formation, ultimately resulting in the formation of neovessels composed of a concentric layers of smooth muscle cells recruited from the neighboring native vessel wall embedded in an extracellular matrix with a monolayer of endothelial cells lining the luminal surface. B. TEVG gross and microscopic morphology changes over time and ultimately resembles the native IVC with a smooth muscle cell layer lined by an endothelial cell layer as shown in gross images and hematoxylin and eosin stained section slides. (Adapted with permission from Roh (2010) [48]).