Repair tendons with silk protein

Anyone who mentions a ruptured Achilles tendon will frown

Tendons are bands of fibrous connective tissue that connect muscles and bones

During the body's natural healing process, tendons and other cells are recruited to rebuild the tendon's original matrix of aligned connective tissue fibers

Possible treatments for tendon injuries include transplanting tendon tissue from the patient or donor, but these carry risks such as infection, graft rejection or necrosis

Another approach is to use mesenchymal stem cells (MSCs), specialized cells that play a key role in tissue regeneration

However, systemic infusion, direct injection, or genetically modified treatments all have their own difficulties: the infusion lacks target specificity to the site of injury, the direct injection requires excessive cell numbers, the genetic modification is inefficient, and the resulting cells Difficult to separate

Another approach is to construct biomaterial frameworks or scaffolds onto which mesenchymal stem cells and growth factors are introduced to generate new tendon tissue

The research team first looked at fibroin, a type of silk protein produced by the silkworm

To improve the tissue regeneration capacity of the scaffolds, the team then paired silk fibroin with GelMA, a gelatin-based water-retaining gel, due to GelMA's biocompatibility, degradability, stiffness, and properties that promote cell attachment and growth ability

"The synergy of GelMA's ability to support regenerative tissue formation and the structural advantages of silk fibroin makes our composite ideal for tendon repair," said TIBI project team leader HanJun Kim, DVM

They prepared mixtures of silk fibroin and GelMA (SG) in different ratios and made them into thin nanofibrous sheets

The optimized SG sheets were seeded on mesenchymal stem cells, and various tests were performed to measure mesenchymal stem cell compatibility and differentiation, production of growth factors, and genetic activity that initiates matrix formation

Compared with silk fibroin sheets without GelMA (SF), the cell viability and proliferation ability of MSCs on SG sheets were improved

The staining results showed that the adhesion rate of mesenchymal stem cells on SG sheets was more than 80%, and the cell adhesion surface was elongated, while the adhesion rate of SF and GelMA was 60%, and spherical cells were only visible on the surface of SF and GelMA

Further testing of growth factors secreted by mesenchymal stem cells implanted in nanofiber sheets showed that growth factors produced by mesenchymal stem cells on SG sheets were best able to repair damaged tendon tissue cultured in a dish
.

Experiments were also performed on live mice with Achilles tendon injuries
.
The MSCs seed nanofiber sheet was implanted into the injury site, and the SG sheet promoted the fastest healing, reduced the injury site, and formed neatly arranged and densely arranged tendon fibers and remodeled muscle components
.

Dr.
Ali Khademhosseini, Director and CEO of TIBI, said: "Tissue remodeling for tendon repair is particularly difficult
.
The work done here greatly advances this achievement
.
"

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