Cardiac patches comprised of embryonic stem cell derived cardiomyocytes (ESC-CMs)
attached to biodegradable polymeric substrates were developed for patients suffering
from heart attacks. Cardiomyocytes were derived from mouse and human embryonic
stem cell (ESC). Thermoplastic elastomeric (TPE) block co-polymers poly(ethylene
terephthalate)/dilionic acid (PET/DLA), a relatively slow degrading biomaterial, served
as substrates to deliver cardiomyocytes and to further support the myocardium after an
infarct. Additionally, titanium dioxide (TiO2) nanoparticles (NPs) (mean size 23 nm),
were incorporated in the PET/DLA polymer in a concentration of 0.2wt%. Results
showed TiO2 NPs to effect polymer mechanical properties, increasing material stiffness
and tensile strength. The surface roughness and hydrophilicity of the biomaterial also
increased upon addition of TiO2 NPs. It was found that 0.2wt% TiO2 NP addition
enhanced cellular adhesion, spread and proliferation. A fibroblastic cell line, used to test
proliferation, proliferated on both biomaterials with and without pre-gelatin coating.
Lactate dehydrogenase (LDH) release into culture media, used as a marker of cell death
did not differ significantly between biomaterials and tissue culture plastic (TCP). The
cytotoxicity of TiO2 NPs on adult cardiomyocytes, hESC-CMs and fibroblasts was also
investigated at various concentrations (0-150 ppm) chosen based on their relevance for
the intended application of the biomaterial. At 10 ppm the particles had no significant
acute effect on cardiac contractility of either adult rat heart cells or hESC-CM.
However, functional activity was significantly reduced, in terms of beating rate, over
longer culture periods (4h). Further improvements were carried out to enhance the
properties of the patch. The investigation included: i) lactide addition to the polymer to
increase polymer degradation rate and ii) topographical surface changes introduced by a
phase separation micromoulding technique (PSμM). Newly developed biomaterial was
faster degrading (as measured by biomaterial %weight loss) and simultaneously
encouraged fibroblast proliferation. Finally the biomaterials have been investigated ex
vivo and in vivo by collaborators at NHLI (Imperial College London). The results have
confirmed that the developed biomaterials in conjunction with cardiomyocytes from
ESCs are promising for applications in myocardial tissue engineering (MTE) strategies
with no adverse effect on cardiac functionality detected.