Nanocomposite Elastomeric Biomaterials for Myocardial Tissue Engineering Using Embryonic Stem Cell‐derived Cardiomyocytes

Abstract

Regeneration or repair of the damaged myocardium requires different strategies including engineered constructs for more efficient cell delivery. This study was undertaken to examine the potential of a new nanostructured elastomer to deliver embryonic stem cell-derived cardiomyocytes (ESC-CM) to an infarcted area of the myocardium. Engineered materials were biocompatible, mechanically stable, and elastomeric nanocomposites serving as substrates for delivery of ESC-CM and as a left ventricular support device in myocardial regeneration strategies. Materials investigated were soft and strong poly(aliphatic/aromatic-ester) multiblock thermoplastic elastomers with poly(ethylene terephthalate) (PET) hard segments and dimerized fatty acid, i.e., dilinoleic acid (DLA) soft segments, respectively, with and without addition of 0.2 wt% TiO 2 nanoparticles to form nanocomposites. The PET/ DLA-TiO 2 nanocomposite exhibited over 8 MPa tensile strength and 900% elongation at break. Addition of TiO 2 nanoparticles significantly altered surface roughness and enhanced adhesion and spreading of ESC-CM derived from mouse and human embryonic stem cells. The newly developed materials did not affect the functional activity of spontaneously beating hESC-CM, as demonstrated by unaltered rate of their beating, and the cells continued to demonstrate contractile activity on the materials for more than two months in culture (the longest time tested). Quantitative proliferation and survival assays using fibroblasts confirmed the ability of the new materials to support cells as well as or better than the present commercial-type thermoplastic elastomer analog. The results indicate that PET/ DLA and PET/DLA-TiO 2 are promising candidates for the manufacture of engineered patches to deliver ESC-CMs.B664

Influence of TiO2 Nanoparticles Incorporated into Elastomeric Polyesters on their Biocompatibility In Vitro and In Vivo

“…The inclusion of 0.2 wt.-% TiO 2 nanoparticles in the PET/DLA matrix appeared to encourage cell adherence and spreading, similarly to our other experiments with human embryonic stem cell-derived cardiomyocytes (hESC-CM), which may be due to changes in surface topography induced by the addition of TiO 2 nanoparticles, as demonstrated in our earlier work. [15] Moreover, such a dependence of the total cell density, total intracellular protein synthesis and smooth muscle cell adhesion on nanometer surface roughness has been observed by other authors. [16,17] Propidium iodide (PI) release -a marker of cell apoptosis and necrosis -was smaller for elastomer containing TiO 2 as compared to the neat elastomer and silicone (Fig.…”

Effect of enzymatic versus titanium dioxide/silicon dioxide catalyst on crystal structure of ‘green’ poly[(butylene succinate)‐co‐(dilinoleic succinate)] copolymers

“…With appropriate selection of these building blocks it is possible to obtain biobased polyesters with a wide range of potential applications such as packaging, fibers, scaffolds and drug delivery systems. [2][3][4] Lipases are enzymes that are widely employed in the biocatalytic synthesis of polymers. [5][6][7][8][9][10] Among these, Candida antarctica lipase B (CAL-B) is the most popular biocatalyst, as it possesses several desirable properties such as high regio-, chemio-and enantioselectivity, broad substrate specificity and commercial availability.…”

“Green” Poly(Butylene Succinate-co-Dilinoleic Succinate) Copolymers Synthesized Using Candida antarctica Lipase B (CAL-B) as Biocatalyst

“…Hard segments are responsible for the dimensional, thermal and mechanical stability of the polymer and the soft segments are designed to impart the elasticity to the material. With appropriate selection of these building sequences it is possible to manufacture biobased copolyesters with desirable properties and wide spectrum of potential applications such as: fibers, films, scaffolds and drug delivery systems [3][4][5].…”