Tissue-engineered constructs
Inventors
Dahl, Shannon L. M. • Niklason, Laura E. • STRADER, Justin T. • Tente, William E. • LUNDQUIST, Joseph J.
Assignees
Publication Number
US-9650603-B2
Publication Date
2017-05-16
Expiration Date
2032-01-06
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The present invention provides constructs including a tubular biodegradable polyglycolic acid scaffold, wherein the scaffold may be coated with extracellular matrix proteins and substantially acellular. The constructs can be utilized as an arteriovenous graft, a coronary graft, a peripheral artery bypass conduit, or a urinary conduit. The present invention also provides methods of producing such constructs.
Core Innovation
The invention provides constructs comprising a tubular biodegradable polyglycolic acid scaffold, wherein the density of the polyglycolic acid is about 45 mg/cc to about 75 mg/cc and is uniform across the entire tubular scaffold. The scaffold is non-woven and may be coated with extracellular matrix proteins, resulting in a substantially acellular construct. The scaffold's dimensions include lengths from about 1 cm to about 100 cm and inner diameters greater than about 3 mm, preferably from about 3 mm to about 20 mm.
The constructs include non-biodegradable polyethylene terephthalate (PET) supports at each end, which allow cell attachment and growth, and the overall construct is substantially free of heavy metal contaminants. The invention also provides methods of producing such constructs by forming a tubular scaffold from a biodegradable PGA sheet through wrapping and entangling fibers at the seam to achieve uniform density and thickness, followed by treatments to remove contaminants and modify degradability. Cells are seeded at low passage levels to secrete extracellular matrix proteins on the scaffold, and then the construct is decellularized to produce a substantially acellular, immune- and calcification-resistant graft with minimal residual polymer.
The problem solved by this invention addresses the unmet clinical need for vascular grafts when patient's own vessels are unavailable or unsuitable due to prior harvest or disease. Existing synthetic grafts like PTFE have poor patency, especially for small-diameter vessels, and alternatives such as decellularized xenografts or allografts have problems with aneurysm, calcification, and thrombosis. Current tissue-engineered grafts either require a long culture period with high costs or lack durability, making them impractical for widespread clinical use. The invention provides rapidly available, cost-effective, mechanically robust, and biocompatible tissue-engineered vascular constructs that resist dilation, calcification, and intimal hyperplasia and can function long term in vivo.
Claims Coverage
The patent includes one independent claim covering a construct with specific scaffold characteristics.
Tubular biodegradable polyglycolic acid scaffold with uniform density and defined dimensions
A tubular biodegradable non-woven polyglycolic acid scaffold having a density of 45 mg/cc to 75 mg/cc, uniform across the entire scaffold, and thickness of 0.8 to 1.2 mm. The scaffold contains polyglycolic acid fibers with thickness 5 to 20 μm, an inner diameter of 3 mm to 6 mm, and length at least 10 cm.
Non-biodegradable polyethylene terephthalate supports at each end
Non-biodegradable polyethylene terephthalate supports are attached at each end of the tubular biodegradable polyglycolic acid scaffold, with porosity greater than 200 cc/min/cm2, permitting attachment and growth of cells.
Substantial removal of heavy metal contaminants
The construct is substantially free of heavy metal contaminants, having only trace amounts of aluminum, barium, calcium, iodine, lanthanum, magnesium, nickel, potassium, and zinc.
Uniformly entangled seam matching scaffold density
The tubular scaffold includes a uniformly entangled seam with a density that matches the overall density of the tubular construct, ensuring structural integrity and uniformity.
Inclusion of extracellular matrix proteins
The construct further comprises extracellular matrix proteins with a thickness greater than 200 micrometers at the thinnest portion of the matrix.
The independent claim covers a tubular biodegradable polyglycolic acid scaffold with uniform density and controlled dimensions, supported at each end by non-biodegradable polyethylene terephthalate supports, substantially free of heavy metals, including extracellular matrix proteins, and having a uniformly entangled seam matching the scaffold density.
Stated Advantages
Constructs are rapidly available with no significant patient wait time since the grafts are pre-manufactured and stored.
The constructs demonstrate mechanical robustness with burst pressures greater than 2000 mmHg and suture strength over 120 g, comparable to native vessels.
Substantial resistance to dilation beyond 50% of implant diameter, aneurysm, calcification, and intimal hyperplasia in vivo.
The constructs are substantially acellular and non-immunogenic, inducing little to no immune response in vivo.
Storage stability allows preservation at about 2° to 30° C. for at least 12 months without loss of mechanical integrity.
Construct dimensions and mechanical features can be customized for various clinical applications including small and large diameter vascular grafts.
Documented Applications
Use as arteriovenous grafts for hemodialysis access in patients with end stage renal disease.
Use as coronary grafts to bypass diseased coronary arteries.
Use as peripheral artery bypass conduits in patients with peripheral arterial disease.
Use as urinary conduits for urinary diversion post-cystectomy as an alternative to ileal conduits.
Use as fallopian tube replacements to address infertility caused by fallopian tube scarring or damage.
Interested in licensing this patent?