Failure Analysis of TEVG’s I: Overcoming the Initial Stages of Blood Material Interaction and Stabilization of the Immune Response

Abstract

Vascular grafts (VG) are medical devices intended to replace the function of a diseased vessel. Current approaches use non-biodegradable materials that struggle to maintain patency under complex hemodynamic conditions. Even with the current advances in tissue engineering and regenerative medicine with the tissue engineered vascular grafts (TEVGs), the cellular response is not yet close to mimicking the biological function of native vessels, and the understanding of the interactions between cells from the blood and the vascular wall with the material in operative conditions is much needed. These interactions change over time after the implantation of the graft. Here we aim to analyze the current knowledge in bio-molecular interactions between blood components, cells and materials that lead either to an early failure or to the stabilization of the vascular graft before the wall regeneration begins.

Failure Analysis of TEVG’s II: Late Failure and Entering the Regeneration Pathway

“…The first interaction of the TEVG with the native tissues and blood is related to the homeostasis maintenance. When the TEVG lacks the required biocompatibility, thrombogenesis and an exacerbated acute inflammatory response are the first causes of TEVG failure [11,15].…”

“…For the TEVG to reach Phase II, the first immune responses should have stabilized with absence of observable occlusion. According to the biomaterial properties, the microstructure and the hemodynamic behavior within the TEVG, the developed pathway is dependent on the recovery of the homeostatic balance in the system to avoid thrombogenesis and induce the immune response stabilization [11]. A functional endothelial layer is imperative to maintain such balance and prevent thrombogenesis, as well as to control the inflammation and the phenotype expression of the cells infiltrating the vascular wall [15,20].…”

“…In both cases, the role of the acute inflammatory response in its ability to recruit endothelial cells and stem cells that will begin the vascular wall remodeling is highlighted. Without a proper initial acute inflammation, the TEVG will not sustain regeneration [11]. For instance, scaffolds with higher pores allow for better cell infiltration, and the immune response can be controlled avoiding chronic inflammation, to identify if the chronic inflammation is avoided and the macrophage-driven degradation is taking place in a controlled mechanism different markers can be analyzed.…”

“…In addition, the failure of TEVGs has a multifactorial origin, so in most cases the preclinical studies do not generally evaluate given the complexity of the regenerative profile, which indicates the limited information of the effect of the implanted TEVGs with the microenvironment. For that reason, the comprise of the cumulative impact of the blood-material-cells interaction seems to have a great impact on the design of future TEVGs with appropriate modulation attributes [11].…”

Blood-Vessel-Inspired Hierarchical Trilayer Scaffolds: PCL/Gelatin-Driven Protein Adsorption and Cellular Interaction

“…Currently, commercially available synthetic vascular grafts are made of several non-biodegradable materials such as polytetrafluoroethylene (PTFE) and polyethylene terephthalate (PET) [ 3 ]. However, their performance is inefficient in replacing small diameter vessels (<6 mm) due to their limited long-term patency with only 32% success after 2 years [ 4 , 5 ] caused by thrombogenic events [ 3 ], intimal hyperplasia [ 6 , 7 ] and/or atherosclerosis [ 8 ], triggering several acute or chronic inflammatory responses [ 6 ].…”