Rapid Engineered Small Diameter Vascular Grafts from Smooth Muscle Cells
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Smooth muscle cells (SMCs) have been extensively used as components in tissue engineered vascular grafts (TEVGs) due to their important roles in vasoactivity and blood vessel remodeling. For TEVG approaches that rely on SMC seeding of a scaffold prior to implantation, few if any utilize a highly-efficient bulk-seeding process to achieve densely and uniformly distributed cells. The objective of this study was to assess a TEVG based on a biodegradable tubular scaffold bulk-seeded with SMCs and cultured acutely in vitro. Rat SMCs were seeded into bi-layered poly(ester-urethane)urea (PEUU) scaffolds using a customized rotational vacuum seeding device. The seeded constructs were dynamically cultured in spinner flasks for 2 days and then implanted into Lewis rats as aortic interposition grafts for 8 weeks. Results showed rSMCs populated the porous layer of the constructs evenly and densely immediately after seeding. The seeding and dynamic culture processes did not affect the metabolic activity and phenotype of the rSMCs. After implantation, rSMC-seeded TEVGs showed a higher patency rate than the unseeded control (75% vs. 37.5% respectively). Patent rSMC-seeded TEVGs revealed extensive tissue remodeling consisting of multiple layers of α-smooth muscle actin- and calponin-positive cells, and a von Willebrand factor-positive monolayer lining the lumen. These results demonstrate the feasibility of quick fabrication of a SMC-based TEVG in vitro and suggest that the cells play a role in maintaining patency of the TEVG as an arterial conduit.
KeywordsTissue engineering Vascular graft Smooth muscle cell Seeding device Scaffold Animal model
- 2.FastStats. Inpatient Surgery. [Web Site] 2003 November 14 [cited 2003 November 22]; Available from: http://www.cdc.gov/nchs/fastats/insurg.htm.
- 6.Hibino N, et al., Late-term results of tissue-engineered vascular grafts in humans. J. Thorac. Cardiovasc. Surg. 139:431–6, 436 e1–2, 2010.Google Scholar
- 9.L’Heureux, N., et al. A completely biological tissue-engineered human blood vessel. FASEB J. 12:47–56, 1998.Google Scholar
- 11.Maul T. Mechanobiology of stem cells: implications for vascular tissue engineering. In: Bioengineering. 2007. Pittsburgh: University of Pittsburgh, p. 345.Google Scholar
- 17.O’Callaghan, C. J., and B. Williams. Mechanical strain-induced extracellular matrix production by human vascular smooth muscle cells—role of TGF-beta(1). Hypertension 36:319–324, 2000.Google Scholar
- 18.Owens, G. K. Regulation of differentiation of vascular smooth muscle cells. Physiol. Rev. 75:487–517, 1995.Google Scholar
- 20.Reusch, P., et al. Mechanical strain increases smooth muscle and decreases nonmuscle myosin expression in rat vascular smooth muscle cells. Circ. Res. 79:1046–1053, 1996.Google Scholar
- 26.Thyberg, J. Phenotypic: Modulation of smooth muscle cells during formation of neointimal thickenings following vascular injury. Histol. Histopathol. 13:871–891, 1998.Google Scholar
- 27.Thyberg, J. Differentiated properties and proliferation of arterial smooth muscle cells in culture. Int. Rev. Cytol. Survey Cell Biol. 169:183–265, 1996.Google Scholar
- 28.WHO. Fact sheet No. 317: cardiovascular diseases. 2010 September 2009 [cited 2010 September 17th]; Available from: http://www.who.int/mediacentre/factsheets/fs317/en/index.html.