title: A study of vascular smooth muscle cell function under cyclic mechanical loading in a polyurethane scaffold with optimized porosity.
abstract: High porosity and pore interconnectivity are important features of a successful tissue engineering scaffold. The objective of this work was to optimize the pore interconnectivity and to increase the porosity of an elastomeric degradable/polar/hydrophobic/ionic (D-PHI) polyurethane porous scaffold while maintaining its mechanical integrity in order to allow for the transfer of mechanical stimulus to vascular smooth muscle cells (VSMCs) seeded onto the scaffold. The effect of varying porogen (sodium bicarbonate (salt) and polyethylene glycol (PEG)) composition and concentration on the mechanical properties, degree of swelling and porosity of the scaffolds was investigated. It was found that the use of 10 wt.% PEG and 65 wt.% salt in scaffold fabrication (D-PHI-75T) resulted in micropore (1-5 μm) formation, a high porosity (79 ± 3%) and mechanical properties (elastic modulus=0.16 ± 0.03 MPa, elongation-at-yield = 31 ± 5% and tensile strength=0.04 ± 0.01 MPa) required to withstand the physiologically relevant mechanical strain experienced by VMSCs in vivo. This study also investigated the influence of cyclic mechanical strain (CMS) on select molecular markers of A10 VSMCs when seeded into the optimized D-PHI scaffold. To study the interaction of A10 cells with the optimized D-PHI-75T scaffold in the presence of uniaxial strain (10%, 1 Hz), a CMS bioreactor was designed and constructed. Molecular marker studies showed a statistical increase in DNA mass and calponin expression after 3 and 7 days of CMS when compared to static samples, indicating that the translation of mechanical loading from the novel polyurethane elastomeric scaffold onto VSMCs will be important to consider with regard to modulating cell phenotype.
authors.affiliation: University of Toronto, Institute of Biomaterials and Biomedical Engineering, Faculty of Dentistry, 124 Edward Street, Room 461, Toronto, Ontario M5G1G6, Canada.
authors.forename: Soroor
authors.initials: S
authors.lastname: Sharifpoor
authors.forename: Craig A
authors.initials: CA
authors.lastname: Simmons
authors.forename: Rosalind S
authors.initials: RS
authors.lastname: Labow
authors.forename: J Paul
authors.initials: JP
authors.lastname: Santerre
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D020342:Finite Element Analysis; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D015151:Immunoblotting; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology; D011140:Polyurethanes / Q000737:chemistry* / Q000494:pharmacology*; D016062:Porosity; D051381:Rats; D013314:Stress, Mechanical; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D009124:Muscle Proteins; D011140:Polyurethanes; D011092:Polyethylene Glycols; D004247:DNA