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.

Emulation of human and rodent cardiac motion with a computer‐controlled cardiac phantom using DENSE MRI

“…The presented work shows that emulation and study of cardiac motion is possible in computer-controlled human and scalable rodent heart phantoms. In addition to commercially used PVA and urethane elastomeric materials, it is also shown that recently synthesized biocompatible PGS materials possess mechanical properties (bulk and surface elasticity; as assessed by DMA measurements) (38,43) that can potentially match the bulk mechanical properties of the in-vivo heart (rat Young Moduli values range between 0.001 and 0.14 MPa and human values between 0.02 and 0.5 MPa) (6,(44)(45)(46)(47)(48)(49)(50)(51)(52). Experimental work with AFM independently confirmed the graded surface stiffness of most of the commercially available elastomers (C-E).…”

Recent Advances in Image-Based Stem-Cell Labeling and Tracking, and Scaffold-Based Organ Development in Cardiovascular Disease

“…Within the realm of SC therapies (including SC-enriched scaffolds, passive 2D-explant membranes [30], 3D extracellular-matrix [ECM] or other biomimetic materials [19,[128][129][130][131], and artificial organs [18]), non-invasive imaging and tracking of labelled cells and their functional impact have taken leading and prominent roles in recent years (Fig. 4).…”

“…In the pursuit of these approaches, increased interest has been documented for identification of biomimetic materials that match local tissue morphology, and mechanical [13,186] and imaging properties [13,187]. As reported by Kossivas et al [130], polymeric or elastomeric materials have traditionally been locally injected or attached and have been found to possess biocompatibility and bioactivity properties that facilitate good adhesion with the surrounding environment, ensuring mechanical stability and proper structural moduli [13], withstanding static and dynamic loading [188]. Recent studies have investigated different classes of scaffold biopolymers as passive epicardial restraint bio-artificial membranes in IHD [13,189] or for controlled delivery of SCs, with and without preconditioning, such as electromechanically synchronous stimulation [187,190].…”

“…Of these, Poly(glycerol sebacate) [PGS] [13,130,191], hydrogels [192], and polyethylene terephthalate [187] have proven to possess excellent biocompatibility, biodegradability, and good stiffness and strength suitable for biological applications [32,[193][194][195], and for use in drug carrier-release applications, both in vitro and in vivo [196].…”

The Roles of Cellular Nanomechanics in Cancer

“…Validation of data obtained by nanoindentation experiments varies and primarily depends on the substrate, instrument condition, and environment used for experiments. Substrates such as glass cover slips, tissue culture polystyrene, chlorapatite single crystals, uncoated or coated with fibronectin/collagen I, poly(glycerol sebacate) elastomers, and poly(lactic‐ co ‐glycolic acid) (PLGA), are conventionally used in nanoindentation procedures. Human cells respond via alterations in their mechanics to the synthetic and biological substrate to which they adhere .…”