Tendons are repaired with Silk Proteins

Tendons are repaired with Silk Proteins ...

Using a fractured Achilles tendon would make anyone wince. Tendon injuries are well-known for their lengthy, difficult and often unreliable healing processes. A large part of all individuals will have a tendon injury, with the risk being greater in women. Besides, those who suffer from this injury are more likely to incur additional injury at the site or miss the rehab fully.

Tendons are formed of fibrous connective tissue that connects muscles to tight bones. This creates a complex interface with a very specific structure. This structure may be altered after an injury, resulting in excess scarring. The tendons may have a different mechanic properties and their ability to bear loads.

During the body''s natural healing processes, tendon and other cells are recruited to reconstruct the tendons'' original matrix of aligned connective tissue fibers. However, this reconstruction may take weeks to months, and the resultant tendon is often imperfect. This result in weakness, chronic pain, and decreased quality of life.

Tenton tissue grafts from patients or donors are being investigated, but these include limitations such as infection, transplant rejection, and necrosis. Synthetic transplants have been attempted, but mechanical, biocompatibility, and biodegradation difficulties have hampered these efforts.

Mesenchymal stem cells are specialized cells that play a vital role in tissue regeneration. At the wound site, they can differ into various cells types and produce signaling molecules which regulate immune response, cellular migration, and new blood vessel formation. This enables tissue regeneration.

However, systemic infusion, direct injection, or genetic modification of MSCs pose their own limitations: infusion lacks particularity to the injury site, direct injection requires prohibitively high cell numbers, and genetic modification is ineffective and produces cells that are difficult to isolate.

Another approach has been to construct biomaterial structures or scaffolds, on which to introduce MSCs and growth factors, in order to produce new tendon tissue. A collaborative team from the Terasaki Institute for Biomedical Innovation (TIBI) has used this approach to develop a technique that has led to significant improvements in MSC tendon regeneration.

Silk fibroin, a silk protein produced by the Bombyx mori silkworm, has been introduced in several biomedical applications, including suture materials, bioengineered ligaments, bone, and even corneal tissue. Because of its superior strength, durability, biocompatibility, and bio-degradative properties, silk fibroin is ideal for use in scaffolds for tendons.

Due to GelMA''s biocompatibility, controllable degradation, stiffness, and ability to promote cell attachment and growth, the team used silk fibroin to match GelMA, a gelatin-based, water-retaining gel.

The synergistic effects of GelMAs'' ability to support regenerative tissue formation and the structural advantages of silk fibroin make our composite material well-suited for tendon repair, according to HanJun Kim, Ph.D., D.V.M, and the TIBIs team leader.

A total of 62 individuals was recruited and experimented with silk fibroin and GelMA (SG) mixtures. They then tested the fiber structures and stretchiness of the sheets and found a suitable formulation with the best mechanical properties. This improved tendon repair.

The optimized SG sheets were separated using MSCs and subjected to various tests to assess MSC compatibility and differentiation, growth factor production, and genetic activity causing matrix formation.

The SG sheets showed an increase in cell viability and proliferation than those on silk fibroin sheets without GelMA (SF). Genetic analysis revealed that relevant gene activity in SG MSCs was significantly increased, in contrast to those on SF sheets, which was reduced.

MSCs on the SG sheets showed a more than 80% attachment rate, as opposed to a 60% attachment rate, with spherically-shaped cells observed on SF and GelMA only surfaces.

Further testing on a growth factor stowed onto nanofiber sheets demonstrates that the MSCs'' growth factors were better able to repair damaged tendon tissue cultivated in a culture dish.

Experiments were also conducted on live rats with damaged Achilles tendons. MSC-seeded nanofiber sheets were implanted onto the injury site and the SG sheets propelled the most accelerated healing, with reduced injury sites and the formation of well-aligned, densely packed tendon fibers and remodeled muscle components.

According to Ali Khademhosseini, the doctor of science and the CEO of the Department of Transportation, tissue remodeling is difficult to complete.

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