Side Effects↓ · Detoxification Function↑... Development of Artificial Liver

Seoul National University College of Veterinary Medicine Research Team

End-stage liver disease is a condition with a very high prevalence worldwide. Liver transplantation is the ultimate life-saving treatment. However, donor organs for liver transplantation are severely lacking globally. A domestic research team has developed an artificial liver with fewer side effects and superior performance.

Seoul National University announced on the 16th that Professor Kyung-Sun Kang's research team from the College of Veterinary Medicine developed an artificial liver technology with significantly enhanced mechanical properties by crosslinking nano-oxidized graphene to a decellularized biological scaffold through peptide bonding.

Image of the human internal organ, the liver.

Artificial livers are proposed as an alternative in the reality of donor organ shortages. However, the liver has highly sophisticated histological microstructures and biochemical characteristics, making reconstruction challenging. As a next-generation technology to overcome these limitations, recellularization technology, which involves removing all cells from animal organs to create decellularized scaffolds and then reintroducing human cells, is gaining attention. This is because it can preserve the microstructure and biochemical properties of the original organ within the scaffold as much as possible. However, when decellularized scaffolds are implanted in vivo, their weak mechanical properties cause them to degrade easily, and the degraded materials induce inflammatory responses.

The research team discovered that nano-oxidized graphene directly inhibits the activity of matrix metalloproteinases (MMPs), enzymes that degrade the scaffold in the body, and enhances the mechanical properties of the scaffold, thereby showing high resistance to enzymatic degradation. Furthermore, when observing the profile of infiltrated immune cells within the graphene-crosslinked scaffold, they found that macrophage polarization toward the M2 phenotype was promoted while polarization toward the M1 phenotype was suppressed, which can alleviate rejection and inflammation occurring after transplantation. In particular, they elucidated that the activity of MMPs expressed by the M2c subtype of M2 macrophages is further inhibited by graphene, protecting the scaffold from in vivo degradation.

The biomimetic artificial liver fabricated with the graphene-crosslinked scaffold was confirmed to have histological structures and functions similar to those of a real liver. When transplanted into mouse models with acute and chronic liver failure, it effectively regenerated the damaged liver and restored liver function.

The research team stated, "This research achievement is significant in that it overcame the limitations of existing biological scaffolds through nano-oxidized graphene crosslinking and developed next-generation tissue engineering technology that maximizes artificial liver transplantation rejection suppression and regenerative capacity." They added, "In the future, we plan to develop various biomimetic artificial organs as alternatives to donor organs, which are expected to be key technologies for extending patients' lives."

The research results were published online on the 13th in the international journal Nature Communications (IF=17.694).

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