A scaffold made
of silk composite functionalised with copper-doped bioactive glass to
facilitate faster bone regeneration has been developed by researchers at Indian
Institute of Technology (IIT) Guwahati. The scaffold seeded with stem cells was
found to differentiate into bone cells, facilitate growth of blood vessels and
successfully integrate the newly formed bone cells with the native bone.
The researchers
were able to replicate the results in rabbits using functionalised non-mulberry
silk composite. Rabbits with scaffolds implanted at the site of bone injury
showed successful growth of bone cells and integration with the native bone at
the end of three months.
Commercially
available synthetic grafts have a failure rate of about 25% and 30-60%
complication rates. This is due to slower bonding with native bone and poor
blood vessel growth.
The team led by
Prof. Biman Mandal from the Department of Bioscience and Bioengineering at IIT
Guwahati developed the silk composite by adding chopped silk fibre to liquid
silk. Unlike pure silk, the silk composite has greater strength. The addition
of bioglass further enhanced the strength of the composite.
Besides other
kinds, both mulberry and non-mulberry silk composites were tested. The
non-mulberry silk composite was found to be superior in all respects. The RGD
sequence in non-mulberry silk is a cell binding site and helps in better cell
attachment and proliferation. As a result, more stem cells get attached to the
composite leading to better bone tissue formation with time.
Suitably
rough
Besides
enhancing the strength of the composite, the minerals from the bioglass gets
deposited on the composite making it rougher. “Bone cells prefer rough surfaces
and the scaffold mimics the native bone surface architecture,” says Prof.
Mandal. Bioglass also helps in stem differentiation. “We found stem cells
differentiating into bone cells with the formation of extracellular matrix
similar to natural bone,” he says.
Doped
copper
The doped copper
plays a crucial role in stabilising the gene responsible for blood vessel
formation. The gene, in turn, regulates the downstream angiogenesic factors
thus helping blood vessel formation.
Copper also
plays a role in attracting endothelial cells (which forms the inner lining of
blood vessels) present nearby to the bone defect site making blood vessel
formation possible.
The mulberry
silk composite degrades and gets desorbed by the body at a faster rate than the
non-mulberry silk. The rate of silk composite degradation should match the rate
of new tissue formation else the bone that forms will tend to be weaker. “The
non-mulberry silk material will be replaced completely in a few years. Since
bone healing is slow, the silk material should not degrade quickly,” Prof.
Mandal says.
The researchers
tested the potential of the composites in repairing bone defects in rabbits and
found more than 80% bone formation at the end of 30 days. “In the rabbits, the
scaffolds promoted new bone tissue formation and growth of blood vessels. The
resorbable nature of the scaffolds enabled them to degrade inside the body
while being replaced with viable bone tissue in the small focal sized bone
defects. No remnants of the scaffold were seen,” says Joseph Christakiran Moses
from the institute’s Department of Bioscience and Bioengineering and first
author of a paper published in the journal Advanced Healthcare Materials.
“The results
from rabbit models are very promising. We would like to undertake trials on
larger animals such as sheep and goat,” says Prof. Mandal. “Since we use green
methodology, the prospects of regulatory clearance are brighter.”
Source:THE HINDU-25th March,2018
