Biomedical Engineering Reference
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treatment gives better results than those by polyethylene glycol,
Triton-X 100, or enzyme-based treatment for decellularizing, and
a fully decellularized whole myocardial construct is obtained by
antegrade coronary SDS perfusion over 12 hours. Treated myocardial
tissue shows histologically no nuclear or contractile element, and
the measured amount of deoxyribonucleic acid (DNA) decreases
less than 4% of that in cadaveric myocardium, while the amount of
glycosaminoglycan is unchanged. In addition, there remain collagen
types I and III, laminin, and fibronectin within the decellularized
tissue, and the fiber composition and orientation of myocardial ECM
are conserved. After the reseeding of cardiac cells, the recellularized
myocardial tissue is cultivated by coronary perfusion in a bioreactor
that simulates and provides a myocardial physiological condition.
At day 4, the synchronous and macroscopic beatings of the tissue
are observed, and at day 8, with a physiological load and electrical
stimulation, the tissue can generate its pumping function, which is
comparable to approximately 2% of adult rat heart function and
25% of 16-week fetal rat heart function, and the myocardial tissue
survives in in vitro cultivation up to 28 days. Immature cross-striated
contractile fibers begin to organize, and the many expressions of
GJ-related protein, connexin-43, within recellularized myocardial
tissue are histologically detected at 8-10 days. The synchronous
beating of the tissue at four days shows that expressed connexin-43
is functional. In addition, re-endothelialization tissue, which forms
single-EC layers in both larger and smaller coronary vessels, is also
fabricated by reseeding ECs into a decellularized construct.
Zhao et al. have fabricated 3D myocardial tissue with characteristic
features similar to the native myocardium by examining (1) the
optimal cell densities of cardiac cells and (2) the concentration of
hydrogel [24]. Engelmayr et al. have prepared a material having
an accordion-like honeycomb microstructure from poly(glycerol
sebacate) (PGS), fabricated a porous elastomeric 3D scaffold with
controllable stiffness and anisotropy from the material, and showed
the feasibility of scaffolds in the reconstruction of myocardial
tissue [25]. Reconstructed myocardial tissue using scaffolds and
neonatal rat cardiac cells shows (1) closely matched mechanical
properties compared to the native myocardium with adequate
stiffness controlled by PGS curing time, (2) cardiac cell contractility
being inducible by an electric field stimulation with directionally
dependent electrical excitation thresholds, and (3) greater cardiac
cell alignment than the control isotropic scaffolds.
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