Silk Fibroin Enhances Tendon Repair and Tissue Regeneration

Researchers at the Terasaki Institute for Biomedical Innovation have used silk protein, which is produced by silkworms, as a biomaterial for tendon repair. The researchers report that their approach has made significant progress in tendon regeneration of mesenchymal stem cells (MSCs).

SF is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity limit its application in regenerative medicine. "At the same time, gelatin-based polymers have advantages in cell attachment and tissue remodeling, but insufficient mechanical strength in regenerating hard tissues such as tendons. Considering these aspects, in this study, gelatin methacryloyl (GelMA) was combined with SF to form a nanofibrous scaffold (SG) with high mechanical strength and strong biological activity."

Possible treatments for tendon injury include transplantation of tendon tissue from the patient or donor, but these carry risks such as infection, graft rejection, or necrosis. Artificial grafting has been attempted, but mechanical, biocompatibility, and biodegradation issues have hindered these efforts.

Another approach is to use MSCs. However, therapeutic approaches using systemic infusion, direct injection, or genetically modified MSCs may result in specific non-targeting to the site of injury, cell numbers, or cell inseparability.

Because of the strength, durability, biocompatibility, and biodegradability of silk fibroin, the team first turned to silk fibroin.

To improve the tissue regeneration ability of the scaffold, the team then paired silk fibroin with GelMA, a gelatin-based hydrogel because of its biocompatibility, degradability, stiffness, and ability to promote cell attachment and growth.

"The ability of GelMA to support the formation of regenerated tissue and the synergistic effect of the structural advantages of fibroin make our composite well suited for tendon repair," said Dr. HanJun Kim, team leader of the TIBI project.

They prepared mixtures of fibroin and GelMA (SG) in different ratios and made them into thin nanofibrous sheets. They then tested the fiber structure and elasticity of the flakes and selected the best formulation with the best mechanical properties. They also observed that fibroin increased the porosity of the material; this contributed to tendon repair.

Compared with silk fibroin sheets without GelMA (SF), MSCs on SG sheets had increased cell viability and proliferation ability. Genetic analysis showed that the related gene activity of SG MSCs was significantly increased, while the related gene activity of SF sheets was decreased.

Further testing of growth factors secreted by mesenchymal stem cells implanted with nanofibrous flakes showed that growth factors produced by mesenchymal stem cells on SG flakes could best repair the injured tendon tissue cultured in culture dishes.

Experiments were also performed on live mice with Achilles tendon injuries.

Dr. Ali Khademhosseini, director and chief executive officer of TIBI, said: "Tissue remodeling of tendon repair is particularly difficult to achieve. The work done here has greatly advanced this achievement."

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