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US 10,934,522 B2Granted
Tissue-engineered constructs
AssigneeHumacyte, Inc.
InventorsShannon L. M. Dahl, Laura E. Niklason, Justin T. Strader, William E. Tente, Joseph J. Lundquist
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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.
Claims12
A method of producing a tubular construct comprising:
- (a) providing a tubular biodegradable polyglycolic acid (PGA) construct having an inner diameter of about 3 mm to about 6 mm and a length of 1 cm to 100 cm, and scouring the tubular PGA construct to remove heavy metal contaminants, wherein the tubular PGA construct comprises entangled PGA fibers, wherein the density of the PGA is about 45 mg/cc to about 75 mg/cc, and wherein said density is uniform across the entire tubular PGA construct,
- (b) seeding human cells at passage 10 or less on the tubular biodegradable polyglycolic acid construct,
- (c) culturing the cells under conditions such that the cells secrete extracellular matrix proteins on the tubular biodegradable polyglycolic acid construct,
- (d) decellularizing the construct in step (c) such that the construct is substantially acellular comprising less than 5% intact cells and wherein the construct is calcification resistant, and
- (e) degrading the polyglycolic acid construct in step (c) such that the polyglycolic acid comprises less than 5% of the cross-sectional area of said construct, wherein the construct induces less than 1 mm of intimal hyperplasia thickening in native vasculature at anastomoses with the construct at 6 months of implantation, and wherein the construct does not dilate greater than 50% beyond its implant diameter after implantation, and wherein the construct has an extracellular matrix protein thickness greater than about 200 μm at the thinnest portion of the construct, thereby producing a decellularized tubular construct.
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Dependencies are inferred from the claim text.