Engineering a Scaffold for Vascular Tissue Regeneration from the Human Amniotic Extracellular Matrix

Date(s) - 11/17/2014
10:00 am

Leslie Goldberg, PhD student

Cardiovascular disease is the leading cause of death worldwide.  Many deaths could be prevented by the availability of long lasting vascular grafts without the need for replacement like those currently available. Small diameter vascular grafts (<6 mm internal diameter) are used in coronary artery bypass graft operations to supply blood to heart tissue affected by myocardial infarctions. Autologous arteries have had the greatest clinical success, but are often not available due to prior usage or severe vascular disease. Autologous venous grafts have limited longevity, with approximately 60% graft failure within 10 years. Synthetic small-diameter grafts tend to develop occlusive thromboses. Thus, there is a pressing need for a widely available, tissue engineered vascular graft.

The amnion, a placental membrane, is typically discarded following delivery and therefore widely available. The material has already achieved clinical success, from corneal ulcer repair to burn management. The McFetridge lab has developed a technique to engineer a tubular scaffold from the extracellular matrix (ECM) of human amniotic membrane (hAM). The hAM is first decellularized and subsequently rolled concentrically around a mandrel into a conduit. Freeze-drying provides initial adhesion of the walls. However, delamination remains a concern, as grafts are initially fragile. Structural stability enhancement is necessary for improved surgical handling and improved ability to withstand physiological hemodynamic forces.

To augment the mechanical integrity of the graft the use of Ludox TM-50 silica nanoparticles (SNPs) as an interfacial adhesive is proposed. Preliminary work has shown that this nanoparticle solution can bind graft layers and prevent interfacial slipping, which is critical given a vascular graft’s exposure to cyclic radial tension. Cytotoxicity, hemocompatibility, and binding strength of SNPs will be investigated. Finally, this work will investigate construct remodeling in 3D biomimetic culture to better understand how to design ECM scaffolds to target specific physiologic mechanical properties.