Engineered vascular tissue fabricated from aggregated smooth muscle cells.
The goal of this study was to develop a system to rapidly generate engineered tissue constructs from aggregated cells and cell-derived extracellular matrix (ECM) to enable evaluation of cell-derived tissue structure and function. Rat aortic smooth muscle cells seeded into annular agarose wells (2, 4 or 6 mm inside diameter) aggregated and formed thick tissue rings within 2 weeks of static culture (0.76 mm at 8 days; 0.94 mm at 14 days). Overall, cells appeared healthy and surrounded by ECM comprised of glycosoaminoglycans and collagen, although signs of necrosis were observed near the centers of the thickest rings. Tissue ring strength and stiffness values were superior to those reported for engineered tissue constructs cultured for comparable times. The strength (100-500 kPa) and modulus (0.5-2 MPa) of tissue rings increased with ring size and decreased with culture duration. Finally, tissue rings cultured for 7 days on silicone mandrels fused to form tubular constructs. Ring margins were visible after 7 days, but tubes were cohesive and mechanically stable, and histological examination confirmed fusion between ring subunits. This unique system provides a versatile new tool for optimization and functional assessment of cell-derived tissue, and a new approach to creating tissue-engineered vascular grafts.
Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Mass., USA.
Tracy A
TA
Gwyther
Jason Z
JZ
Hu
Alexander G
AG
Christakis
Jeremy K
JK
Skorinko
Sharon M
SM
Shaw
Kristen L
KL
Billiar
Marsha W
MW
Rolle
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D001807:Blood Vessel Prosthesis; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
D001672:Biocompatible Materials
Cardiovasc Res. 2004 Sep 1;63(4):719-30
15306228
Arterioscler Thromb Vasc Biol. 1996 Jun;16(6):821-9
8640411
Tissue Eng Part A. 2010 May;16(5):1737-47
20038201
Biomaterials. 2009 Mar;30(8):1542-50
19111338
Am J Pathol. 1994 May;144(5):1068-81
8178930
J Biomed Mater Res A. 2003 Sep 1;66(3):550-61
12918038
Biotechniques. 2007 Oct;43(4):494, 496-500
18019341
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11915-20
17615237
Tissue Eng. 2007 Nov;13(11):2601-13
17961004
J Thorac Cardiovasc Surg. 1998 Mar;115(3):536-45; discussion 545-6
9535439
Science. 1986 Jan 24;231(4736):397-400
2934816
Tissue Eng Part A. 2010 Jun;16(6):2051-61
20109063
Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1451-60
15486037
Biomaterials. 2008 Mar;29(7):825-33
18035412
Tissue Eng. 2007 Aug;13(8):2087-94
17518713
Biomaterials. 2009 Apr;30(12):2164-74
19176247
Biomacromolecules. 2006 Nov;7(11):2942-8
17096517
Ann Biomed Eng. 2003 Sep;31(8):937-49
12918909
Ann Biomed Eng. 2000 Apr;28(4):351-62
10870892
Biomaterials. 2007 Apr;28(13):2183-91
17280714
Matrix Biol. 2003 Jun;22(4):339-50
12935818
FASEB J. 2008 Aug;22(8):2853-61
18385214
FASEB J. 1998 Jan;12(1):47-56
9438410
Nat Med. 2006 Mar;12(3):361-5
16491087
Am J Physiol Heart Circ Physiol. 2004 Jul;287(1):H46-53
15001442
Biomaterials. 2009 Oct;30(30):5910-7
19664819
Ann Biomed Eng. 2007 Mar;35(3):348-55
17206488
Lancet. 2009 Apr 25;373(9673):1440-6
19394535
J Biotechnol. 2010 Jul 1;148(1):46-55
20223267
Science. 1999 Apr 16;284(5413):489-93
10205057
Basic Res Cardiol. 1994 Sep-Oct;89(5):397-410
7535519