The revolutionary device that helps frogs regenerate their legs

A revolutionary new device could help frogs fend off their legs and could lead to treatments for spinal cord injuries, according to the latest research.

Scientists have designed the "bioreactor" that can induce partial regeneration of hind limbs in adult African aquatic frogs with claws by "reviving" tissue repair at the amputation site.

Their results, published in the journal Cell Reports, introduce a new model for testing "electroceuticals", or cell-stimulating therapies.

Lead author of the study, Dr. Michael Levin, a developmental biologist at the Allen Discovery Center at Tufts University in the United States, said, "At best, adult frogs do not grow back normally. only in the form of a thin cartilaginous tip, without relief

"Our procedure has induced a regenerative response that they do not normally have, resulting in larger and more structured appendages.

"The bioreactor device has generated very complex results downstream that bioengineers can not yet manage directly."

Scientists printed the silicon bioreactor in 3D and filled it with hydrogel – a sticky polymer globe.

They associated with hydrating hydrating silk proteins that promote healing and regeneration, and then added progesterone, best known for its role in preparing the uterus for pregnancy.

But it has also been shown that the hormone promotes the repair of nerves, blood vessels and bone tissue.

The researchers divided the frogs into three groups: experimental, control and sham.

For the experimental and simulated group, they stitched the device on the frogs immediately after limb amputation.

In the experimental group, the bioreactor released progesterone at the site of amputation. In any case, they removed the devices after 24 hours.

When they examined the frogs of the experimental group at different times over a period of nine and a half months, they found that the bioreactor seemed to trigger a degree of limb regeneration not seen in the other groups.

Instead of a typical tip-shaped structure, bioreactor treatment resulted in a blade-shaped formation closer to a fully formed limb that could not generate unassisted regeneration.

Dr. Levin said, "The bioreactor device has created a favorable environment for the wound, in which the tissue could develop as during embryogenesis.

"A very brief application of the bioreactor and its payload triggered months of tissue growth and structuring."

When Dr. Levin and his team took a closer look at the regenerated structures, they found that, unlike the control and dummy groups, the regenerating members of the bioreactor-treated frogs were thicker, their bones developed, their innervation and their vascularization .

By analyzing video footage of frogs in their tanks, they also noticed that frogs could swim more like frogs without pretension.

Further analysis revealed that the bioreactor had altered gene expression occurring in the cells of the amputation site.

Dr. Levin explained that genes involved in oxidative stress, serotonergic signaling, and white blood cell activity were upregulated, while other genes related to signaling were downregulated.

Scientists also observed that scars and immune responses were downregulated in bioreactor-treated frogs, suggesting that the added progesterone attenuated the body's natural response to the lesions, thereby promoting the regeneration process.

The first author of the study, Dr. Celia Herrera-Rincon, a neuroscientist at Dr. Levin's lab at Tufts University, said, "In both reproduction and its new role in the functioning of the brain, the actions of the progesterone are local or tissue-specific.

"What we are demonstrating with this approach is perhaps that reproduction, brain processing and regeneration are closer than we think.

"Maybe they share paths and elements of a common bioelectrode – and up to now, not completely understood -."

Dr. Levin said his team would continue to target bioelectric processes to induce spinal cord regeneration and reprogramming of the tumor.

They also hope to replicate their mammalian bioreactor experience.

Previous research suggests that mice can partially regenerate amputated fingertips in good conditions, but their life on the ground hampers the process.

Dr. Levin added, "Almost all good regenerators are aquatic.

"You can imagine why this is important: a mouse that loses a finger or a hand and then grinds the delicate regenerative cells in the flooring material when it moves, is unlikely to experience significant limb regeneration. . "

He now plans to add sensors to the device for remote monitoring and stimulation, hoping to improve control of cellular decision-making after an injury.