ECM-based materials in cardiovascular applications: Inherent healing potential and augmentation of native regenerative processes

Abstract

The in vivo healing process of vascular grafts involves the interaction of many contributing factors. The ability of vascular grafts to provide an environment which allows successful accomplishment of this process is extremely difficult. Poor endothelisation, inflammation, infection, occlusion, thrombosis, hyperplasia and pseudoaneurysms are common issues with synthetic grafts in vivo. Advanced materials composed of decellularised extracellular matrices (ECM) have been shown to promote the healing process via modulation of the host immune response, resistance to bacterial infections, allowing re-innervation and reestablishing homeostasis in the healing region. The physiological balance within the newly developed vascular tissue is maintained via the recreation of correct biorheology and mechanotransduction factors including host immune response, infection control, homing and the attraction of progenitor cells and infiltration by host tissue. Here, we review the progress in this tissue engineering approach, the enhancement potential of ECM materials and future prospects to reach the clinical environment.

Keywords: extracellular matrix; healing; native regenerative processes; vascular graft.

Figure 1.

Pathways of monocyte differentiation during interaction with synthetic and ECM materials.

Figure 2.

Chemoattractive bioactivity of ECM degradation products. During the ECM remodeling process (due to activity of macrophages, SMC), degradation products are released into the blood stream these recruit multipotent progenitor cells (MPCs) from bone marrow by chemoattractant activity of the peptides and degradation products. The circulating progenitor cells (CPCs) then migrate to the site of implantation and aid in the endothelisation process.

Figure 3.

The effect of sub-endothelial substrate on the activation pattern of pro-inflammatory cellular mechanisms of mechanotransduction. This figure illustrates the biochemical processes induced by fluid shear stress for both a synthetic material and ECM scaffold material. As fluid flows across the EC layer (depicted in red), the mechanosensors at the endothelium surface sense the stress and react by transmitting signals through the transmembrane integrins (illustrated in red and blue). Specific integrin mechanotransduction pathways are thus activated, sending messages from ‘inside-out’ through specific integrins, triggering certain responses. Depending on which type of integrin is activated, various responses occur. Synthetic materials are prone to stimulate a pro-inflammatory response of adhered cell [217] and exposed to the flow, in which presentation on the surface of vascular endothelium of adhesion molecules (for example VCAM-1) induce a subsequent attraction, rolling and adhesion and subsequent attachment of leukocytes to the site.

Figure 4.

Illustration by the Belgian anatomist Andreas Vesalius, highlighting the similarities in the arborisation of the vascular and nervous networks. Vessels (red) and nerves (green). [227], Copyright, Reprinted with permission from the Nature Publishing Group.