Tissue Engineered Vessel Composed of Electrospun Scaffold in a Bioreactor System with Decellularization and Endothelial Seeding

Track Code: 
16KU051M
Summary: 
This invention is a tubular electrospun scaffold of natural protein gelatin and synthetic polyglycolic acid (PGA) / poly-lactic-co-glycolic (PLGA) polymers in a bioreactor system connected to a flow circuit and seeded with cultured fibroblasts and endothelial cells.
Overview: 
Cardiovascular disease is commonly associated with narrowing or blockage of blood vessels leading to reduced blood flow and potential vessel blockage/ critical limb ischemia (CLI). As a result, cardiac and peripheral bypass surgeries are often required for blood vessel replacement. Current transplant options include autologous grafts, allografts, or xenografts. These grafts have significant limitations with concerns over long term functionality and viability. Although synthetic grafts are available as alternatives, satisfactory results have only been demonstrated in large/medium diameter arteries and are often of limited use in smaller vessels due to possible reocclusion and poor patency. Tissue engineering is an alternative approach for creating new vascular grafts in which cells are seeded or encapsulated in scaffolds and produce ECM while the polymer is degraded. Although scaffolds from decellularized tissue polymers and biodegradable synthetic polymers have been developed, their clinical use has been limited by the inability to mimic the mechanical properties of native tissue and long term patency and growth required for in vivo function. Outcomes with alternative graft materials (cadaveric vein and plastic grafts) are often poor in patients with critical limb ischemia resulting in graft failure and subsequent amputation of the affected limb.
Applications: 
Bypass graft for patients requiring lower leg bypass for revascularization.
How it works: 
The tubular electrospun scaffold is composed of the natural polymer gelatin and the synthetic polymer PGA/PLGA in a bioreactor system connected to a flow circuit seeded with cultured human fibroblasts to form a cellular, tubular structure which is subsequently decellularized and seeded with endothelial cells from peripheral blood circulating cells. The tubular conduits are prepared using a custom designed electrospinning apparatus which includes a syringe pump, a high-voltage supply, and a rotating collection mandrel.
Benefits: 
Electrospinning is a flexible technique which may address current limitations of synthetic grafts as it can fine tune the biological and mechanical properties of fibers by varying mixture composition, not commonly feasible with other scaffold fabrication methods.
Why it is better: 
The proposed technology is the first description of an electrospun scaffold for vessel grafts in combination with a bioreactor and allows for potentially shorter lead time and more flexible mechanical properties compared to the current tissue engineerd grafts. Compared to other technologies which use autologous cells to generate the engineered vessel, the proposed technology is also less invasive and negates donor site morbidity with greater graft availability. The use of both synthetic and natural polymers imparts significant strength to the graft with biocompatibility.
Other Applications: 
In the absence of endothelial cell seeding, the technology could also be used as a biliary or ureter conduit for patients requiring repair to a bile duct or ureter. This invention may also used for the fabrication of other vascular constructs for which the combined use of electrospinning and a bioreactor system are appropriate.
Licensing Associate: 
Aswini Betha, PhD · abetha@ku.edu · 913-588-5713
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