No abstract

Microfabricated poly(glycerol sebacate) (PGS) scaffolds may be applicable to tissue engineering heart valve leaflets by virtue of their controllable microstructure, stiffness, and elasticity. In the current study, PGS scaffolds were computationally designed and microfabricated by laser ablation to match the anisotropy and peak tangent moduli of native bovine aortic heart valve leaflets. Finite element simulations predicted PGS curing conditions, scaffold pore shape, and strut width capable of matching the scaffold effective stiffnesses to the leaflet peak tangent moduli. Based on simulation predicted effective stiffnesses of 1.041 MPa and 0.208 MPa for the scaffold preferred (PD) and orthogonal, cross-preferred (XD) material directions, scaffolds with diamond-shaped pores were microfabricated by laser ablation of PGS cured 12 hours at 160°C. Effective stiffnesses measured for the scaffold PD (0.83 ± 0.13 MPa) and XD (0.21 ± 0.03 MPa) were similar to both predicted values and peak tangent moduli measured for bovine aortic valve leaflets in the circumferential (1.00 ± 0.16 MPa) and radial (0.26 ± 0.03 MPa) directions. Scaffolds cultivated with fibroblasts for 3 weeks accumulated collagen (736 ± 193 μg/g wet weight) and DNA (17 ± 4 μg/g wet weight). This study provides a basis for the computational design of biomimetic microfabricated PGS scaffolds for tissue engineered heart valves.

Microfabricated poly(glycerol sebacate) (PGS) scaffolds may be applicable to tissue engineering heart valve leaflets by virtue of their controllable microstructure, stiffness, and elasticity. In the current study, PGS scaffolds were computationally designed and microfabricated by laser ablation to match the anisotropy and peak tangent moduli of native bovine aortic heart valve leaflets. Finite element simulations predicted PGS curing conditions, scaffold pore shape, and strut width capable of matching the scaffold effective stiffnesses to the leaflet peak tangent moduli. Based on simulation predicted effective stiffnesses of 1.041 MPa and 0.208 MPa for the scaffold preferred (PD) and orthogonal, cross-preferred (XD) material directions, scaffolds with diamond-shaped pores were microfabricated by laser ablation of PGS cured 12 hours at 160°C. Effective stiffnesses measured for the scaffold PD (0.83 ± 0.13 MPa) and XD (0.21 ± 0.03 MPa) were similar to both predicted values and peak tangent moduli measured for bovine aortic valve leaflets in the circumferential (1.00 ± 0.16 MPa) and radial (0.26 ± 0.03 MPa) directions. Scaffolds cultivated with fibroblasts for 3 weeks accumulated collagen (736 ± 193 μg/g wet weight) and DNA (17 ± 4 μg/g wet weight). This study provides a basis for the computational design of biomimetic microfabricated PGS scaffolds for tissue engineered heart valves.

Cyclic flexure and stretch are essential to the function of semilunar heart valves and have demonstrated utility in mechanically conditioning tissue-engineered heart valves. In this study, a cyclic stretch and flexure bioreactor was designed and tested in the context of the bioresorbable elastomer poly(glycerol sebacate). Solid poly(glycerol sebacate) membranes were subjected to cyclic stretch, and micromolded poly(glycerol sebacate) scaffolds seeded with porcine aortic valvular interstitial cells were subjected to cyclic stretch and flexure. The results demonstrated significant effects of cyclic stretch on poly(glycerol sebacate) mechanical properties, including significant decreases in effective stiffness versus controls. In valvular interstitial cell-seeded scaffolds, cyclic stretch elicited significant increases in DNA and collagen content that paralleled maintenance of effective stiffness. This work provides a basis for investigating the roles of mechanical loading in the formation of tissue-engineered heart valves based on elastomeric scaffolds.

One of the oldest and best known developmental screening tests was recently restandardized and revised as the Denver-II. Because it was published without evidence of its accuracy, the present study was undertaken with 104 children between 3 and 72 months of age attending one of five day-care centers. To determine the presence of developmental problems, children were administered individual measures of intelligence, speech-language, achievement, and adaptive behavior. A second psychological examiner, blind to the outcome of the diagnostic battery, administered the Denver-II. Developmental problems including language impairments, learning disabilities, mild mental retardation, and/or functional developmental delay were found in 17% of the children. The Denver-II identified correctly 83% and thus had high rates of sensitivity. However, more than half the children with normal development also received abnormal, questionable, or untestable Denver-II scores. Thus the test had limited specificity (43%) and a high overreferral rate. The alternative scoring method, categorizing questionable/untestable scores as normal, caused sensitivity to drop to 56% although specificity rose to 80%. Since neither scoring method produced acceptable levels of accuracy, an effort was made to locate the sources of accuracy and inaccuracy within the test. Only items in the language domain were modestly helpful in discriminating children with and without difficulties. The findings suggest that the authors of the Denver-II need to engage in further development of the instrument including revising scoring criteria and item placement in relation to children's ages. In the interim, test users should employ screening tests which are more accurate such as the Minnesota Inventories or the Battelle Developmental Inventory Screening Test.