13 May 2022

Silk Tendons

Tendon injuries are well known for their lengthy, difficult and often incomplete healing processes. It is estimated that 30% of all people have had or will have a tendon injury, with women at the highest risk.

Tendons are fibers of connective tissue that attach muscles to bones. Soft tissue (tendons) connected to hard (bones) creates a complex system, and after injury this specific structure is disrupted, and connective tissue turns from a linear formation into a spirally twisted one. Excessive scarring may also occur, altering the mechanical properties of the tendon and weakening resistance to stress.

For proper healing, it is necessary to restore the original structure of the tendon from straight fibers of connective tissue. But this reconstruction can take from several weeks to several months, and as a result, the tendon is often imperfect. This leads to incomplete recovery of motor function, chronic pain and a decrease in the patient's quality of life.

Possible methods of treating tendon injuries include transplantation of own or donor tissues, but this is accompanied by the risk of infection, graft rejection or necrosis. Attempts were made to transplant artificial material, but mechanical problems, problems of biocompatibility and biodegradation did not allow using this method.

Another approach is to use mesenchymal stem cells, which play a key role in tissue regeneration. At the wound site, they can differentiate into different cell types and produce signaling molecules that regulate the immune response, cell migration and the formation of new blood vessels; this ensures tissue regeneration.

However, treatment methods using intravenous infusion, direct injection into a wound or genetic modification of mesenchymal stem cells are also associated with difficulties: with systemic administration, cells do not accumulate at the site of injury, direct injection requires an excessively high number of cells, and genetic modification is ineffective and produces cells that are difficult to isolate.

Another approach is to create scaffolds seeded with mesenchymal stem cells with growth factors to generate new tissue. A research team from the Terasaki Institute of Biomedical Innovation used this approach to develop a method that would significantly improve tendon regeneration.

Silk fibroin, a protein produced by the Bombyx mori silkworm, was chosen as the basis. It is used for the production of fabrics and tailoring, in optical and electronic devices, as well as in biomedicine – from suture materials to the creation of bioengineered ligaments, bones and even corneal tissues. Due to its superior strength, durability, biocompatibility and biodegradation, silk fibroin is ideal for use in wireframes.

To improve the ability of the skeleton to regenerate tissues, the group combined silk fibroin with a polymer (gelatin-methacryloyl) – gel based on gelatin, which has biocompatibility, controlled degradation, rigidity and the ability to enhance the fixation and growth of stem cells. The synergistic effect of gelatin-methacryloyl's ability to support tissue regeneration and the structural advantages of silk fibroin make the composite material suitable for tendon repair.

The researchers prepared a mixture with an optimal ratio of silk fibroin and gelatin-methacryloyl (SG7) and made thin nanofiber plates from it. They noticed that silk fibroin gives the material increased porosity, which enhances tendon repair. SG7 plates were seeded with mesenchymal stem cells. Mesenchymal stem cells on SG7 plates showed high viability and active proliferation compared to those on silk fibroin plates without gelatin-methacryloyl (SF). Genetic analysis showed that the corresponding gene activity in the new material was significantly higher than on SF plates.

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Staining tests showed that mesenchymal stem cells in SG7 showed a higher rate of attachment and had an oblong shape; cells on SF were spherical.

Growth factors secreted by mesenchymal stem cells were able to repair damaged tendon tissue grown in vitro. Experiments were also conducted on live rats with damaged Achilles tendons. SG7 nanoplates were implanted into the injury site, and they contributed to faster healing with the formation of smooth, straight, tightly packed tendon fibers and muscle components.

Article Y.Xue et al. Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration is published in the journal Small.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Terasaki Institute: Repairing Tendons with Silk Proteins.


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