The
3D patch has high cell density, a foremost requirement for heart tissue
Scientists at the Indian Institute of Technology (IIT)
Guwahati have fabricated a 3D cardiac tissue patch using silk protein membranes
seeded with heart muscle cells. The patch can potentially be used for
regenerating damaged heart tissue.
“The 3D patch that we fabricated can be implanted at
the site of damage to help the heart regain normal function. It can also be
used for sealing holes in the heart,” says Biman Mandal from the Department of
Biosciences and Bioengineering, IIT Guwahati, who led the research.
Cardiac tissue gets permanently damaged when oxygen
supply is reduced or cut off during a heart attack. The damaged portion gets
scarred and does not contract and relax, which over time leads to a change in
the shape of the heart and reduced pumping capacity.
While currently available grafts fail to mimic the
structure and the function of the native heart tissue as well as maintain high
cell numbers, the patch developed by the IIT Guwahati researchers scores over
these on many counts. The results were published in the Journal of Materials Chemistry B.
The team led by Prof. Mandal tested both mulberry (Bombyx
mori) and non-mulberry (Antheraea assama) silk to fabricate
the membrane. Silk proteins extracted from raw silk were used for fabricating
the membrane by using a mould. The nano-groove structure on the mould was
transferred to the silk membrane and this helped guide the heart muscle to grow
in a linear fashion and parallel to each other thus mimicking the heart tissue
structure. “We focused on developing a silk-based tissue engineered membrane
which will allow the cardiac cells to grow while maintaining the structural
anisotropy,” says Prof. Mandal.
Seeding
the silk
Heart cell lines and cells taken from the heart tissue
were used for seeding the silk membrane. The presence of certain cell-binding
protein sequences (RGD motifs) and greater surface roughness of the
non-mulberry silk, which is endemic to north-east India (locally called muga
silk), facilitated better anchorage and cell binding. “The cells grew and
proliferated, filling the membrane 7-10 days after it was seeded,” he says.
As heart tissue continuously contracts and relaxes,
the engineered tissue should have good elasticity. “The muga silk exhibited
good elasticity and mechanical strength comparable to native heart tissue as we
used only 2% silk proteins to make the membrane,” says Shreya Mehrotra,
Department of Biosciences and Bioengineering and first author of the paper.
“When tested on mice, we found the muga silk was immunologically compatible and
hence not rejected by the immune system,” she adds.
Making
a 3D patch
The single membranes with proliferating cells were
then stacked one over the other to form a 3D patch. “In 5-6 days, the cells
present on top of the membrane bound to the membrane above it leading to the
layers sticking to each other,” Prof. Mandal says.
“Stacking the membranes to form a 3D patch overcomes
the drawbacks of current scaffolds used for cardiac tissue engineering in terms
of creating a high cell dense anisotropic patch, a foremost requirement for
this tissue,” he stresses.
The silk in the patch supports the cells till the
newly formed cardiac tissue integrates with the native heart tissue and
degrades once the integration takes place. “This method is better than the
conventional direct delivery of cardiac cells to repair the damaged portion of
the heart as the cells get washed out from the injected site,” says Ms.
Mehrotra.
The
team will carry out animal studies in collaboration with AIIMS.
Source: THE HINDU-13th August,2017
