TISSUE ENGINEERING SCAFFOLDS
The present invention relates to tissue engineering scaffolds (TE scaffolds) that mimic the biomechanical behavior of native blood vessels, tissue engineered blood vessels (TEBVs) derived from the TE scaffolds, and methods of making and using the TE scaffolds and TEBVs.
1 . A method of making a tissue engineering (TE) scaffold comprising the steps of:
(a) providing a first tubular element comprising an elastomeric element, an exterior surface, an interior luminal surface, and a first diameter;
(b) dilating the first tubular element to a second diameter;
(c) providing a second tubular element comprising a tensile element, an exterior surface and an interior luminal surface, on the surface of the dilated first tubular element of step (b);
(d) bonding the dilated first tubular element of step (b) and the second tubular element; and
(e) decreasing the second diameter of the first tubular element to the first diameter of step (a) to form the TE scaffold.
2 . The method of claim 1 wherein the second tubular element is corrugated.
3 . The method of claim 2 wherein the corrugated second tubular element comprises a fibrous network in which the fiber direction is oriented circumferentially.
4 . The method of claim 1 wherein the providing step of (a) comprises electrospinning on a mandrel.
5 . The method of claim 1 wherein the providing step of (c) comprises electrospinning on a mandrel.
6 . The method of claim 1 wherein the providing step of (c) comprises placing a pre-formed second tubular element over the dilated first tubular element of step (b).
7 . The method of claim 1 wherein the elastomeric element comprises an elastomeric component with a first elastic modulus and the tensile element comprises a tensile component with a second elastic modulus that is greater than the first elastic modulus.
8 . The method of claim 7 wherein the second elastic modulus is greater than the first elastic modulus by at least one order of magnitude.
9 . The method of claim 1 wherein the elastomeric element comprises a natural elastomeric component.
10 . The method of claim 1 wherein the elastomeric element comprises a synthetic elastomeric component.
11 . The method of claim 1 wherein the elastomeric element comprises a natural elastomeric component and a synthetic elastomeric component.
12 . The method of claim 9 or 11 wherein the natural elastomeric component is selected from the group consisting of elastin, resilin, abductin, and silk.
13 . The method of claim 10 or 11 wherein the synthetic elastomeric component is selected from the group consisting of latex, a polyurethane (PU), polycaprolactone (PCL), poly-L-lactide acid (PLLA), polydiaxanone (PDO), poly(L-lactide-co-caprolactone) (PLCL), and poly(etherurethane urea) (PEUU).
14 . The method of claim 1 wherein the tensile element comprises a natural tensile component.
15 . The method of claim 1 wherein the tensile element comprises a synthetic tensile component.
16 . The method of claim 1 wherein the tensile element comprises a natural tensile component and a synthetic tensile component.
17 . The method of claim 14 or 16 wherein the natural tensile component is collagen, cellulose, silk, and keratin.
18 . The method of claim 15 or 16 wherein the synthetic tensile component is selected from the group consisting of nylon, Dacron® (polyethylene terephthalate (PET)) Goretex® (polytetrafluoroethylene), polyester, polyglycolic acid (PGA), poly-lactic-co-glycolic acid (PLGA), and poly(etherurethane urea) (PEUU).
19 . A tissue engineering scaffold having a mechanical response to stress and strain substantially similar to that of a response by a native blood vessel, the scaffold comprising (a) a first tubular element comprising an elastomeric element, an exterior surface and an interior luminal surface; and (b) a second tubular element comprising a tensile element, an exterior surface and an interior luminal surface in contact with the exterior surface of the first tubular element, wherein the mechanical response of said tissue engineering scaffold to stress and strain is characterized by a J-shaped stress/strain curve.
20 . A tissue engineering scaffold having a mechanical response to stress and strain substantially similar to that of a response by a native blood vessel, the scaffold comprising (a) a first tubular element comprising an elastomeric element, an exterior surface and an interior luminal surface; and
(b) a second tubular element comprising a tensile element, an exterior surface and an interior luminal surface in contact with the exterior surface of the first tubular element, wherein the tissue engineering scaffold has at least one of
(i) a circumferential tube elastic modulus 1 of about 0.1 MPa to about 0.5 MPa,
(ii) a circumferential tube elastic modulus 2 of about 3.0 MPa to about 6.0 MPa; and
(iii) a circumferential modulus transition of about 0.57 to about 1.12.
21 . The tissue engineering scaffold of claim 20 wherein the scaffold is characterized by a J-shaped stress/strain curve.
22 . The tissue engineering scaffold of claim 19 or 20 wherein the second tubular element is corrugated.
23 . The tissue engineering scaffold of claim 22 wherein the corrugated second tubular element comprises a fibrous network in which the fiber direction is oriented circumferentially.
24 . The tissue engineering scaffold of claim 19 or 20 wherein the elastomeric element comprises an elastomeric component with a first elastic modulus and the tensile element comprises a tensile component with a second elastic modulus that is greater than the first elastic modulus.
25 . The tissue engineering scaffold of claim 24 wherein the second elastic modulus is greater than the first elastic modulus by at least one order of magnitude.
26 . The tissue engineering scaffold of claim 19 or 20 wherein the elastomeric element comprises a natural elastomeric component.
27 . The tissue engineering scaffold of claim 19 or 20 wherein the elastomeric element comprises a synthetic elastomeric component.
28 . The tissue engineering scaffold of claim 19 or 20 wherein the elastomeric element comprises a natural elastomeric component and a synthetic elastomeric component.
29 . The tissue engineering scaffold of claim 26 or 28 wherein the natural elastomeric component is selected from the group consisting of elastin, resilin, abductin, and silk.
30 . The tissue engineering scaffold of claim 27 or 28 wherein the synthetic elastomeric component is selected from the group consisting of latex, a polyurethane (PU), polycaprolactone (PCL), poly-L-lactide acid (PLLA), polydiaxanone (PDO), poly(L-lactide-co-caprolactone) (PLCL), and poly(etherurethane urea) (PEUU).
31 . The tissue engineering scaffold of claim 19 or 20 wherein the tensile element comprises a natural tensile component.
32 . The tissue engineering scaffold of claim 19 or 20 wherein the tensile element comprises a synthetic tensile component.
33 . The tissue engineering scaffold of claim 19 or 20 wherein the tensile element comprises a natural tensile component and a synthetic tensile component.
34 . The tissue engineering scaffold of claim 31 or 33 wherein the natural tensile component is selected from the group consisting of collagen, cellulose, silk, and keratin.
35 . The tissue engineering scaffold of claim 32 or 33 wherein the synthetic tensile component is selected from the group consisting of nylon, Dacron® (polyethylene terephthalate (PET)) Goretex® (polytetrafluoroethylene), polyester, polyglycolic acid (PGA), poly-lactic-co-glycolic acid (PLGA), and poly(etherurethane urea) (PEUU).
36 . The tissue engineering scaffold of claim 19 or 20 , which has at least one of the following:
(i) a pore gradient where the pore diameter gradually decreases from about 100 microns at the exterior surface of the second tubular element to about 5 to about 15 microns at the interior surface of the first tubular element;
(ii) a circumferential tube toughness of about 0.45 MJ/m 3 to about 1.0 MJ/m 3 ;
(iii) an axial tube toughness of about 0.1 MJ/m 3 to about 0.5 MJ/m 3 ;
(iv) a tangent delta of about 0.05 to about 0.3; and
(v) a storage modulus of about 400 MPa to about 0.12 MPa.