prominent in regions of increased stiffness, MMP sensitivity, and immobilized YRGDS. Conclusions: We developed a novel technique that generates tunable mechanical and biochemical gradients in scaffolds that stimulate directed 3D neovascularization in vitro. http://dx.doi.org/10.1016/j.carpath.2013.01.017 Evaluation of elastin-derived vascular grafts in a circulatory model Deon Bezuidenhout a , Tim Pennel a , George Fercana b , Peter Zilla a , Dan Simionescu b a Cardiovascular Research Unit, University of Cape Town b Department of Bioengineering, Clemson University Purpose: To evaluate pentagalloyl-glucose (PGG) stabilized elastin- derived vascular grafts (EDVGs) in terms of their suitability as vascular substitutes. Methods: EDVGs were prepared by alkaline decellularization (0.1 M NaOH at 37°C for 3 h), rinsing and sterilization in 0.1% peracetic acid. Batches of EDVG scaffolds were treated with sterile 0.1% PGG (pH 5.5) containing 20% isopropanol for 24 h, rinsed and stored in sterile PBS. A subset of PGG and non-PGG samples were additionally covalently heparinized via diamine coupling and reductive amination using nitrous acid degraded heparin. Grafts were implanted in a rat infrarenal aortic model for 4 and 8 weeks. Remodeling, patency, endothelialization and healing of the explants were determined by gross and histological evaluation. Results: While PGG treatment did not significantly affect the denaturation temperature (DT) of the tissue, heparinization resulted in significant increases in DT (from 52°C to 81–82°C) and heparin content (from baseline noise levels of b10 mg/g to N100 mg/g). Overall the nonheparinized groups showed strong evidence of remodeling and recellularization, with a high patency rate of 82%. At 8 weeks, only small fragments of the original grafts were preserved with good neovessel formation and moderate intimal hyperplasia (IH). The heparinized groups showed 100% patency, but with little remodeling, presumably due to the increased crosslink density resulting from the amination of the tissue prior to heparin attachment. Some surface endothelialization was observed in all treatment groups. Conclusions: EDVGs are promising candidates as vascular grafts, either as substrates for remodeling, or in more highly cross-linked and heparinized forms. http://dx.doi.org/10.1016/j.carpath.2013.01.018 Tissue engineering of aortic valve leaflets using biomimetic composite poly(ethylene glycol) diacrylate hydrogels Xing Zhang, Bin Xu, Hubert Tseng, Maude L. Cuchiara, Jennifer L. West, K. Jane Grande-Allen Rice University, Houston, TX Purpose: To develop anisotropic poly(ethylene glycol) diacrylate (PEGDA) hydrogels using two different molecular weight PEGDA molecules by the photolithographic patterning replicating mechan- ical behavior of aortic valve leaflets; To functionalize PEGDA hydrogels with bioactive peptides mimicking the biological function of aortic valve leaflets. Methods: PEGDA hydrogels were prepared by photo cross-linking. Stripe-patterned hydrogels were created by photolithographic pat- terning of secondary PEGDA molecules into the network of a preformed hydrogel. Mechanical property was evaluated by compres- sion, tension and three-point bending tests. Bioactive peptides (cell- adhesive and matrix metalloproteinase-sensitive peptides) were incorporated into the hydrogel network. Interaction of valvular interstitial cells with these biomimetic PEGDA hydrogels was investigated in both two-dimensional and three-dimensional cultures. Results: PEGDA hydrogels showed tunable mechanical property depending on the molecular weight of PEGDA and concentration of the prepolymer solution. Higher stiffness was obtained using higher concentration or lower molecular weight of PEGDA. Several photo- lithographic patterned hydrogels showed significantly different modulus when tested parallel and perpendicular to the stripe pattern under tension and bending condition (anisotropy). Bioactive peptides incorporated in the hydrogel network facilitate valvular cell adhesion and proliferation. Conclusions: PEGDA hydrogels are suitable as scaffolds for engineer- ing of aortic valve leaflets, considering they can be tuned mimicking the mechanical behavior of the leaflets, and functionalized with bioactive peptides to support valvular cell adhesion and proliferation. Moreover, PEGDA hydrogels provide a blank template for studying interaction between valvular cells and extracellular matrices, which will shed light on valvular biology and provide cues for future heart valve tissue engineering. http://dx.doi.org/10.1016/j.carpath.2013.01.019 Numerical assessment of the strain/stress fields supported by microstructural components of mouse carotid arteries Chiara Bellini a , Jacopo Ferruzzi b , Elena S. Di Martino a , Jay D. Humphrey b a University of Calgary, Calgary, AB, Canada b Yale University, New Haven, CT, USA Purpose: The arterial wall is a collection of independently growing elements, including cells and ECM components. Residual strains allow these elements to achieve their homeostatic working point, while simultaneously ensuring material continuity of the tissue. Macroscopic measures of residual strains were previously reported in terms of opening angle, i.e. the angle between the midpoint and the tips of a radially cut arterial ring. The purpose of this study was to develop a numerical model capable of predicting the strain/stress distribution at the microstructural level under general configurations of the external loads. Methods: Pressure-diameter tests were performed on carotid arteries from wild-type mice to record the mechanical response. Histological assays provided the relative abundance of constituents. A structu- rally-motivated constitutive relationship was fitted to the mechanical data and fed to the numerical model. Opening angle measurements served as model validation. Results: The model uses experimental measures of macroscopic mechanical and structural properties to estimate the strain/stress fields for each microstructural constituent. Results represent the first quantitative demonstration that loads within the physiological range are mainly supported by the elastic material in the artery, while collagen fibers intervene at higher pressures, in agreement with qualitative observations previously reported. Conclusion: Understanding the contribution of microstructural components in withstanding the external loads might clarify the mechanotransduction mechanisms through which cells sense and react to changes in the macroscopic mechanical environment. Also, it might help in estimating the intensity of perturbations that either Abstracts / Cardiovascular Pathology 22 (2013) e29–e52 e32