A new hydrogel can be directly injected into muscle to help it regenerate

**SPEAKER_1** (0:00)
The Nature Podcast is supported by Nature+, a flexible monthly subscription that grants immediate online access to the science journal Nature and over 50 other journals from the Nature portfolio. More information at go.nature.com/plus.

**SPEAKER_3** (0:30)
I find this not only refreshing but at some level astounding.

**Nick Petruccio** (0:42)
Welcome back to The Nature Podcast. This time, a gel to replace and regenerate muscles.

**Shamini Bundell** (0:48)
And why starfishes have such strange body plans. I'm Shamini Bundell.

**Nick Petruccio** (0:53)
And I'm Nick Petruccio.
What if you could replace a damaged muscle with a stand-in that can help you move whilst also helping the tissues repair? Well, that's something the researchers publishing this week in Nature are trying to make a reality, with an injectable hydrogel solution.

**Mikyung Shin** (1:22)
We developed a new type of the hydrogel for recovering the muscle and nerve tissues.

**Nick Petruccio** (1:30)
That's Mikyung Shin, part of the team behind this new paper. We're going to hear more from her in a moment, but first a little background. Muscles, like any other tissue, can get injured, and severe injuries can leave the muscle, and you, unable to move. And yet, muscles which are not used can waste away, and that can make healing very challenging.
There are a range of options to deal with this, but all have their drawbacks. For example, mechanical exoskeletons can be used to help people move, but they don't actually help the muscle heal. Alternatively, there are a range of devices that electrically stimulate muscles to help them move, or even seek to replace damaged tissue. But often these devices are stiff, and cannot be applied to small, awkward-to-reach places.
Ideally, the solution would be flexible, able to stimulate the muscles to help their recovery, and promote tissue repair. And that's where hydrogels come in. These are soft materials that can be theoretically applied directly into the damaged tissue, in tight crevices which are tricky for other materials, where they can help aid in healing. Here's Mick Young again.

**Mikyung Shin** (2:45)
Hydrogels are very similar to our biological tissues. Our tissue have a lot of water in that, and hydrogel have also a lot of water in that, so they can mimic our biological tissue environment and can trigger the cellular behaviour or cellular growth for our tissue repair.

**Nick Petruccio** (3:08)
Effectively, Mick Young believes that hydrogels could almost act as a stand-in for muscles and help them repair. They also have the added benefit of being injectable, which means clinicians could avoid surgery which can damage the surrounding tissue.
However, hydrogels still have drawbacks of their own, and so Mick Young and her team set about overcoming them. Firstly, hydrogels don't have great conductivity, which makes stimulating them to help muscles move more difficult. Their solution uses some clever chemistry. She was able to link the backbone of the hydrogel to other compounds that hold gold ions.

**Mikyung Shin** (3:49)
In that case, the gold ion can generate the gold nanoparticles. That gold nanoparticle can provide the electrical conductivity very stably to our hydrogels.

**Nick Petruccio** (4:02)
And that allowed the hydrogel she created to be conductive, allowing muscles to be stimulated and thus used, which helps promote healing and helps the patient to move. But that wasn't the end of the problems. Next one is strength.
Hydrogels tend to be pretty, well, weak, and so don't last well in the body. In fact, in the moving and strained tissue that is muscle, they are at risk of leaking out.
This is a particularly sticky problem, as making them too strong would make them inflexible and unable to be injected into the body. Mick Young and the team needed something flexible and strong. So they went back to the chemistry drawing board and looked to something called biphenyl bonds.

**Mikyung Shin** (4:47)
We hypothesized that the biphenyl bonds can be different for simple carbon-carbon bonds. So we think the biphenyl rings can be rearranged during the syringe injections compared to the carbon-carbon bonds.

**Nick Petruccio** (5:04)
Unlike a standard carbon-carbon bond, which is fixed, Mick Young thought that these biphenyl bonds would be able to break during injection of the hydrogel. But then reform afterwards, making the gel weak enough to be injected, but then strong again once it's in the body.
A hypothesis that they demonstrated worked, first in simulations, then studies with cells, and finally in experiments with rats.

**Mikyung Shin** (5:29)
We prepared the rat models with a very severe muscle injury, and then we fill our hydrogel into that area, the injured area.

**Nick Petruccio** (5:39)
With the rats, the team wanted to check two things. First, how well the hydrogel would be able to conduct electrical signals to work as a stand-in while their muscles heal, and second, they wanted to see how well it can help the rat's muscles actually regenerate.