I-Corps: Tissue-engineering vascular grafts using autologous cell sheets

Trustees Of Boston University, Boston

Investigators

Abstract

There are approximately 10 million people in the US with peripheral vascular disease (PVD), and 460,000 vascular bypass surgeries are performed annually using either synthetic or autologous venous grafts. Saphenous vein, the most commonly used autograft material, has a 50% failure rate within 18 months due to intimal hyperplasia. For patients who no longer have veins available for bypass, the vascular surgeon must use synthetic grafts (PTFE or Dacron) which are associated with a higher rate of complications such as occlusion and infection. Furthermore, these synthetic grafts can typically only be used to bypass vessels with an internal diameter greater than 6 mm. The proposed technology/product consists of a novel cell sheet-derived engineered autologous vascular graft that can meet this urgent clinical need for biologically responsive vascular grafts. This has the potential to overcome the current problems of autologous and synthetic grafts: limited supply; restricted length of autologous grafts, and poor biocompatibility of synthetic grafts. The proposed cell sheet culture and stacking system was optimized to produce biologically responsive, living vascular grafts at low-cost. Confluent and self-assembled cell sheets of any physiologically relevant cell type, size and 2D pattern can be achieved within 10 days after seeding. Hydrogel substrate stiffness, which fundamentally affects cell phenotype and behavior, can be accurately matched to the stiffness of individual layers of the vessel, e.g. tunica media or tunica adventitia. Cell sheets grown on a hydrogel substrate platform demonstrate high cell viability and a high degree of native tissue recapitulative properties (e.g. blood vessel) such as cell alignment, extracellular matrix composition, and mechanical strength. The cell sheet stacking and rolling process preserves individual cell sheet patterns and cell viability (>99%) to produce structurally and biologically similar vascular graft. This system is scalable for high throughput manufacturing processes to lower the cost and fabrication time. Fully vascularized three-dimensional living tissue remains an unsolved challenge in tissue engineering. The proposed system can be utilized for the design of tissue replacements that require complex structures for proper tissue function. This versatile technology may be further expanded beyond the current cardiovascular application to create tissue engineered solutions for other disease states.