Could we cure paralysis? Revolutionary device that allowed frogs to regenerate lost limbs has fuelled hopes of one day treating spinal cord injuries

  • Progesterone is associated withenhancing recovery and regeneration 
  • Frogs with this hormone in to a device for 24 hours had legs grow back better
  • Its enhanced healing could be used to treat spinal cord injuries, claim scientists
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Frogs with amputated legs had enhanced limb regeneration when fitted with a revolutionary device. 

Scientists claim this so-called ‘bioreactor’ helps the animals regrow legs by ‘kick-starting’ the advanced healing process using the hormone progesterone. 

Progesterone is crucial to pregnancy and it is now believed that the chemical could help find a cure for spinal cord injuries.

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Scientists claim this so-called ‘bioreactor’ helps the animals regrow legs by ‘kick-starting’ the advanced healing process using the hormone progesterone

Adult aquatic African clawed frogs were fitted with a specialist  ‘bioreactor’ that uses the hormone progesterone to improve healing.  

Findings, published today in the Journal Cell Reports, introduce a new model for testing ‘electroceuticals’ – or cell-stimulating therapies.

Study senior author Dr Michael Levin, developmental biologist at Tufts University, said: ‘At best, adult frogs normally grow back only a featureless, thin, cartilaginous spike

‘Our procedure induced a regenerative response they normally never have, which resulted in bigger, more structured appendages.

‘The bioreactor device triggered very complex downstream outcomes that bioengineers cannot yet micromanage directly.’

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The scientists 3D printed the bioreactor out of silicon and filled it with hydrogel – a sticky glob of polymers.

They laced the hydrogel with hydrating silk proteins that promote healing and regeneration before adding progesterone.

Progesterone is a steroid hormone which is best known for its pivotal role in the menstrual and ovulation cycle performed every month by women. 

It is also known to promote nerve, blood vessel, and bone tissue repair.

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

For the experimental and sham group, they sutured the device on the frogs immediately after limb amputation.

In the experimental group, the bioreactor released progesterone onto the amputation site. In all cases, they removed the devices after 24 hours.

When they looked at frogs in the experimental group at different stages over nine-and-a-half months.

The team witnessed the bioreactor instigated a degree of limb regeneration not observed in the other groups.

Instead of a spike-like structure, the bioreactor treatment resulted in a paddle-like growth that resembled a fully formed limb.

Dr Levin said: ‘The bioreactor device created a supportive environment for the wound where the tissue could grow as it did during embryogenesis.

‘A very brief application of bioreactor and its payload triggered months of tissue growth and patterning.’

When Dr Levin and his team took a closer look at the regenerated structures they saw that, unlike in the control and sham groups, the limbs of the bioreactor-treated frogs were thicker with more developed bones, innervation, and vascularisation.

The team also analysed video footage of the frogs in their tanks found the frogs treated with progesterone could swim more like unamputated frogs. 

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

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


Progesterone is a hormone that is secreted by the corpus luteum, a temporary endocrine gland that the female body produces after ovulation.

It prepares the body for the possibility of pregnancy after ovulation. 

It causes a thickening of the uterus lining to allow for an egg to embed into the wall. 

After a woman’s cycle is completed and they are not pregnant the gland breaks down and the menstrual cycle begins. 

If a woman does become pregnant the chemical continues to be produced to maintain the layer and provide oxygen to the developing fetus.  

Said to be ‘oestrogen’s cousin’ or the ‘relaxing hormone’, is thought to help to maintain pregnancy.

It is not typically prescribed on the NHS in the UK unless a woman has three or more miscarriages in a row.

If progesterone levels are too low with regard to estrogen levels, a woman will experience sleep disturbances, irritability, anxiety, weight gain, breast swelling, breast tenderness, and itching, bloating, sweating, loss of memory, and loss of libido. 

Despite its widespread use in pregnancy the hormone has also been shown to promote nerve, blood vessel, and bone tissue repair. 

This has therefore brought around applications in tissue regeneration.  

The researchers also observed that scarring and immune responses were downregulated in the bioreactor-treated frogs, suggesting that the added progesterone dampened the body’s natural reaction to injury in a way that benefited the regeneration process.

Dr Celia Herrera-Rincon, a neuroscientist in Dr Levin’s lab at Tufts University, said: ‘In both reproduction and its newly discovered role in brain functioning, progesterone’s actions are local or tissue-specific.

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

‘Maybe they share pathways and elements of a common–and so far, not completely understood – bioelectrical code.’

The team also analysed video footage of the frogs in their tanks found the frogs treated with progesterone could swim more like unamputated frogs. Further analysis revealed that the bioreactor had altered the gene expression occurring in cells at the amputation site

Dr Levin said his team will continue to target bioelectric processes for inducing spinal cord regeneration and tumour reprogramming.

They also hope to replicate their bioreactor experiment in mammals.

Previous research suggests that mice can partially regenerate amputated fingertips in the right conditions, but their life on land hinders the process.

Dr Levin added: ‘Almost all good regenerators are aquatic.

‘You can imagine why this matters: a mouse that loses a finger or hand, and then grinds the delicate regenerative cells into the flooring material as it walks around, is unlikely to experience significant limb regeneration.’

Now he plans to add sensors to the device for remote monitoring and stimulation, which he hopes will improve control over cellular decision making after injury.

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