title: MRI-based morphological modeling, synthesis and characterization of cardiac tissue-mimicking materials.
abstract: This study uses standard synthetic methodologies to produce tissue-mimicking materials that match the morphology and emulate the in vivo murine and human cardiac mechanical and imaging characteristics, with dynamic mechanical analysis, atomic force microscopy (AFM), scanning electron microscopy (SEM) and magnetic resonance imaging. In accordance with such aims, poly(glycerol sebacate) (PGS) elastomeric materials were synthesized (at two different glycerol (G)-sebacic (S) acid molar ratios; the first was synthesized using a G:S molar ratio of 2:2, while the second from a 2:5 G:S molar ratio, resulting in PGS2:2 and PGS2:5 elastomers, respectively). Unlike the synthesized PGS2:2 elastomers, the PGS2:5 materials were characterized by an overall mechanical instability in their loading behavior under the three successive loading conditions tested. An oscillatory response in the mechanical properties of the synthesized elastomers was observed throughout the loading cycles, with measured increased storage modulus values at the first loading cycle, stabilizing to lower values at subsequent cycles. These elastomers were characterized at 4 °C and were found to have storage modulus values of 850 and 1430 kPa at the third loading cycle, respectively, in agreement with previously reported values of the rat and human myocardium. SEM of surface topology indicated minor degradation of synthesized materials at 10 and 20 d post-immersion in the PBS buffer solution, with a noted cluster formation on the PGS2:5 elastomers. AFM nanoindentation experiments were also conducted for the measurement of the Young modulus of the sample surface (no bulk contribution). Correspondingly, the PGS2:2 elastomer indicated significantly decreased surface Young's modulus values 20 d post-PBS immersion, compared to dry conditions (Young's modulus = 1160 ± 290 kPa (dry) and 200 ± 120 kPa (20 d)). In addition to the two-dimensional (2D) elastomers, an integrative platform for accurate construction of three-dimensional tissue-mimicking models of cardiac anatomy from 2D MR images using rapid prototyping manufacturing processes was developed. For synthesized elastomers, doping strategies with two different concentrations of the MRI contrast agent Dotarem allowed independent and concurrent control of the imaging characteristics (contrast and relaxivity) during the synthetic process for increased contrast agent absorption, with tremendous potential for non-destructive in vivo use and applications to cardiovascular and cerebrovascular diseases.
authors.affiliation: Laboratory of Physiology and Biomedical Imaging, Department of Mechanical and Manufacturing Engineering, School of Engineering, University of Cyprus, Nicosia, Cyprus.
authors.forename: Fotis
authors.initials: F
authors.lastname: Kossivas
authors.forename: S
authors.initials: S
authors.lastname: Angeli
authors.forename: D
authors.initials: D
authors.lastname: Kafouris
authors.forename: C S
authors.initials: CS
authors.lastname: Patrickios
authors.forename: V
authors.initials: V
authors.lastname: Tzagarakis
authors.forename: C
authors.initials: C
authors.lastname: Constantinides
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry*; D003651:Decanoates / Q000737:chemistry*; D055119:Elastic Modulus; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008422:Materials Testing / Q000379:methods; D051379:Mice; D032383:Myocytes, Cardiac / Q000737:chemistry* / Q000502:physiology*; D011108:Polymers / Q000737:chemistry*; D013314:Stress, Mechanical; D013718:Tensile Strength
chemical_list: D003651:Decanoates; D011108:Polymers; C469892:poly(glycerol-sebacate); D005990:Glycerol