Tissue engineered blood vessel
Inventors
Cooper, Kevin • Chun, Iksoo • Colter, David C. • Dhanaraj, Sridevi • Gosiewska, Anna • Seyda, Agnieszka • Fang, Carrie H. • YANG, CHUNLIN
Assignees
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Abstract
Compositions and methods of using tissue engineered blood vessels to repair and regenerate blood vessels of patients with vascular disease are disclosed.
Core Innovation
The invention relates to tissue engineered blood vessels (TEBVs) for repairing diseased blood vessels. The TEBVs include a biocompatible, bioabsorbable scaffold combined with one or more of cells, cell sheets, cell lysate, or minced tissue.
The scaffold includes poly(p-dioxanone) and other polymer combinations, collagen, crosslinked collagen, and an acellular omental matrix. The scaffold can be formed into a tubular construct, including an electrospun tubular scaffold of randomly oriented fibers, and can be fabricated using electrospinning, lyophilization, and textiles/foams and composites with surface coatings.
A disclosed approach for constructing the TEBV includes providing a scaffold comprising a solution of poly(p-dioxanone) and 1,1,1,3,3,3-hexafluoro-2-propanol solvent formed as an electrospun tubular scaffold of randomly oriented fibers, cutting the electrospun tubular scaffold to form a scaffold sheet, seeding the scaffold sheet with cells, rolling the seeded sheet into a tube, and culturing the tube in a bioreactor.
The disclosure characterizes performance properties including mechanical strength, hemocompatibility, and degradability, and describes example data associated with attachment/growth and improved cellular outcomes. It also describes in vivo implantation in a dog model in connection with femoral arteries and provides device use contexts including AV grafting and CABG/coronary and peripheral applications.
Claims Coverage
The provided independent claim specifies 5 inventive features centered on an electrospinning-based method with a defined scaffold chemistry/solvent configuration, followed by conversion of the tubular scaffold into a seeded, rolled tube and bioreactor culturing.
Electrospun tubular scaffold from poly(p-dioxanone) in 1,1,1,3,3,3-hexafluoro-2-propanol
Providing a scaffold comprising a solution of poly(p-dioxanone) and 1,1,1,3,3,3-hexafluoro-2-propanol solvent formed as an electrospun tubular scaffold of randomly oriented fibers.
Sheet cutting of the electrospun tubular scaffold
Cutting the electrospun tubular scaffold to form a scaffold sheet.
Cell seeding of the scaffold sheet
Seeding said scaffold sheet with cells.
Rolling seeded sheet into a tube
Rolling said seeded sheet into a tube.
Bioreactor culturing of the rolled tube
Culturing the tube in a bioreactor.
Overall, the claim coverage centers on preparing an electrospun, randomly oriented-fiber PDO tubular scaffold using a specified PDO/HFIP solvent system, converting it into a scaffold sheet, seeding it with cells, rolling it into a tube, and culturing the assembled tube in a bioreactor.
Stated Advantages
Improved cellular outcomes with hUTC and lysate-augmented scaffolds.
Bioreactor-based static/dynamic (flow/pulsatile pressure) culture supports attachment/growth.
Mechanical strength, hemocompatibility, and degradability are characterized as performance properties.
Documented Applications
Repairing diseased blood vessels using tissue engineered blood vessels (TEBVs).
Device use contexts include AV grafting and CABG/coronary and peripheral applications.
In vivo dog implantation in femoral arteries is described in connection with patency.
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