Physiologic Pulsatile Flow Bioreactor Conditioning of Poly(ethylene glycol)-based Tissue Engineered Vascular Grafts
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Mechanical conditioning represents a potential means to enhance the biochemical and biomechanical properties of tissue engineered vascular grafts (TEVGs). A pulsatile flow bioreactor was developed to allow shear and pulsatile stimulation of TEVGs. Physiological 120 mmHg/80 mmHg peak-to-trough pressure waveforms can be produced at both fetal and adult heart rates. Flow rates of 2 mL/sec, representative of flow through small diameter blood vessels, can be generated, resulting in a mean wall shear stress of ∼6 dynes/cm2 within the 3 mm ID constructs. When combined with non-thrombogenic poly(ethylene glycol) (PEG)-based hydrogels, which have tunable mechanical properties and tailorable biofunctionality, the bioreactor represents a flexible platform for exploring the impact of controlled biochemical and biomechanical stimuli on vascular graft cells. In the present study, the utility of this combined approach for improving TEVG outcome was investigated by encapsulating 10T-1/2 mouse smooth muscle progenitor cells within PEG-based hydrogels containing an adhesive ligand (RGDS) and a collagenase degradable sequence (LGPA). Constructs subjected to 7 weeks of biomechanical conditioning had significantly higher collagen levels and improved moduli relative to those grown under static conditions.
KeywordsTransmural strain Transmural shear Hydrogel Material properties Medial equivalents
The authors would like to acknowledge funding from the NIH and NSF and a Whitaker Foundation Graduate Research Fellowship to MKM. We thank Jane Grande-Allen, PhD for advice regarding mechanical testing and biochemical analyses, and Marcella Estrella for her technical assistance.
- 13.Clerin, V. et al. Tissue engineering of arteries by directed remodeling of intact arterial segments. Tissue Engineering 9: 2003.Google Scholar
- 16.Fung, Y. C. Biomechanics: Mechanical Properties of Living Tissues. New York: Springer-Verlag, 1993.Google Scholar
- 17.Gobin, A. S., and J. L. West. Cell migration through defined, synthetic extracellular matrix analogues. FASEB J. 16:2002.Google Scholar
- 28.Kanda, K., and T. Matsuda. Mechanical stress induced cellular orientation and phenotypic modulation of 3D cultured smooth muscle cells. ASAIO 39: 1993.Google Scholar
- 29.Kempczinski, R. (ed.) Vascular Surgery. Denver: WB Saunders, 2000.Google Scholar
- 31.Ku, D., and C. Zhu. The mechanical environment of the artery. In: Hemodynamic Forces and Vascular Cell Biology, edited by B. Sumpio. Austin: RG Landes Company, 1993, pp. 1–23.Google Scholar
- 39.Posey, J., and L. Geddes. Measurement of the modulus of elasticity of the arterial wall. Cardiovasc. Res. Ctr. Bull. 11:83–88, 1973.Google Scholar