What has silk got to do with a slipped disc? Early-stage research at the Indian Institute of Technology-Delhi (IITD) potentially points to a key role for the shiny protein fibre in the attempt to find a solution to the painful vertebral injury that affects millions across the globe.
Silk fibres are being researched for various tissue engineering techniques like developing a ligament but the IITD study is the first to use them as a scaffold to replicate the anatomical alignment of cells in the outer part of a inter-vertebral disc (IVD) tissue.
A slipped disc condition refers to the degeneration of an IVD tissue, the tissues found between each vertebra of the spine that give it the flexibility to bend and turn in different directions. As people age, the water-rich cartilage that forms the core of an IVD dehydrates and becomes rigid, pushing out the surrounding fibrous tissue called the annulus fibrosis (AF). The AF, in turn, puts pressure on surrounding nerves, causing pain.
In a paper published by India?s National Academy of Sciences, scientists at the IITD?s textile technology department demonstrated that a tissue-engineered IVD constructed using silk fibre and nasal chondrocyte (cartilage from the nose) cultures was as strong as an IVD from a goat while still being flexible enough.
Replacing a degenerated IVD with a ceramic disc is the common medical treatment for the condition, but the rigid structure could transfer the load to neighbouring discs, says IITD assistant professor Sourabh Ghosh, who specialises in tissue engineering. Attempts have been made by scientists to regenerate AF tissues using scaffolds made of other material but they do not simulate the fibre alignment accurately, he says.
?For IVD, this is probably the first report in which we are orienting the silk-fibre alignment in different layers in criss-cross pattern simulating anatomical orientation,? says Ghosh. ?For this particular tissue we need very high elastic property and flexibility. Silk has wonderful mechanical strength compared to many other polymers, so we thought it would be an ideal candidate.?
In the paper, by lead author Maumita Bhattarcharjee, the researchers demonstrated the construction of an IVD by culturing the hydrogel and then surrounding it with a few layers of silk fibre using a special winding machine that replicate the alignment of the AF. They then used human nasal cartilage, obtained from donors, to develop the disc scaffold.
Their silk-fibre alignment helped the cells attach and grow along the specific direction necessary to replicate the tissues. The strength of the IVD satisfactorily matched that of a disc from a goat that was freshly obtained from a local slaughterhouse, says Ghosh. But he points out that a goat?s disc cannot be directly compared with a human spine, which is vertical and also because each IVD has a different dimension.
In a second paper that has been submitted for publication, the team has reported that they were able to modify the surface chemistry of the silk scaffolds, by attaching bioactive molecules to produce type-II collagen and aggrecan, the proteins that make up the robust cartilage tissues, like in the IVD.
Ghosh says the next step would be to apply for permission to conduct animal trials, before which they will have to prove that the IVD is compatible to immune cells. ?We are planning to start some experiments from January in Switzerland. First we have to prove that our IVD is absolutely bio-comfortable and it should not activate any immune cells,? he says. The project is funded by the department of science and technology and the Indian Council of Medical Research.
Silk fibres have been widely tested for engineering tissues such as blood vessels, articular cartilage, meniscal tissue and bone because of its excellent bio-compatibility and mechanical properties, says Deepa Ghosh, group head of the tissue engineering department at Reliance Life Sciences. ?Due to its high thermal stability, silk biomaterials have the unique property to allow its processing over a wide range of temperatures up to about 250?C without the loss of functional integrity.?
Regenerative medicine includes various technologies involving tissue-specific cells (somatic cells), stem cells and tissue-engineered products aimed at treating many diseases that result from the damage of terminally differentiated cells. ?Perhaps the most potential application of this technology is to treat diseases such as Alzheimer, bone and spinal cord injury, stroke, heart diseases, diabetes, osteoarthritis and rheumatoid arthritis.? says Deepa Ghosh, adding that donated organs and tissues are often used to replace ailing or destroyed tissues but the need far outweighs the supply. ?Researchers are trying to create organs such as urinary bladder and liver in the lab with the hope that one day these would do away with the need for organ donors.?
Tissue engineering essentially means using a stem cell or a somatic cell together with a bio-degradable scaffold, which, being a three-dimensional structure, helps the cell better produce the extra-cellular matrix, says Anish Sen Majumdar, chief scientific officer at Stempeutics, a Bangalore-based stem cell research company.
?Extensive research is currently going on throughout the world to understand which particular cell… either stem cell or embryonic stem cell or mesenchymal stem cell or some cells that are not stem cells but differentiated cells… would be best for what treatment,? says Majumdar. ?We are trying to figure out that what cells, along with what scaffold would be the best application for a particular disease.?