Tissue-engineered constructs
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.
1. A decellularized tubular construct comprising human extracellular matrix proteins and polyglycolic acid, wherein the human extracellular matrix proteins have a thickness greater than 200 μm at the thinnest portion of the tubular construct, wherein the tubular construct has an internal diameter of >3 mm, wherein the tubular construct is calcification resistant, wherein the polyglycolic acid comprises less than 5% of the cross-sectional area of said tubular construct, wherein the tubular construct is an acellular construct comprising less than 5% intact cells, wherein the length of the tubular construct is 1 cm to 100 cm, wherein the tubular construct induces less than 1 mm of intimal hyperplasia thickening in native vasculature at anastomoses with the construct at 6 months of implantation, wherein the tubular construct does not dilate greater than 50% beyond its implant diameter after implantation, wherein the burst pressure is at least 2000 mm Hg, wherein the suture strength is greater than 90 g, and wherein the tubular construct is substantially free of heavy metal contaminants.
2. The tubular construct of claim 1 , wherein the tubular construct compromises less than 1% intact cells.
3. The tubular construct of claim 1 , wherein the tubular construct is impermeable to fluid leakage up to at least 200 mm Hg.
4. The tubular construct of claim 1 , wherein the tubular construct is selected from the group consisting of an arteriovenous graft, a coronary graft, diseased peripheral artery bypass conduit, fallopian tube replacement and a urinary conduit.
5. The tubular construct of claim 1 , wherein the extracellular matrix proteins comprise hydroxyproline at >40 μg/mg dry weight.
6. The tubular construct of claim 1 , wherein the tubular construct comprises trace amounts of double stranded genomic DNA.
7. The tubular construct of claim 1 , wherein the tubular construct induces less than 1% calcification within 6 months of implantation.
8. The tubular construct of claim 4 , wherein the tubular construct is a urinary conduit, and the urinary conduit tolerates exposure to urine for at least 4 weeks.
9. The tubular construct of claim 1 , wherein the tubular construct is stable in storage at 2° to 30° C. for at least 12 months.
10. The tubular construct of claim 1 , wherein the heavy metal contaminant is selected from the group consisting of aluminum, barium, calcium, iodine, lanthanum, magnesium, nickel, potassium and zinc.
11. The tubular construct of claim 1 , wherein the length of the tubular construct is 10 cm to 100 cm.
12. The tubular construct of claim 1 , wherein the length of the tubular construct is 10 cm to 40 cm.
13. The tubular construct of claim 1 , wherein the internal diameter of the tubular construct is 3 mm to 6 mm.