Our body connects us to the world. When people lose parts of their bodies to traumatic illness or injury, they often feel like they’ve lost a part of who they are, or even suffer a loss. grief similar to the loss of a loved one.
Their sense of personal loss is justified because unlike salamanders or sarcastic comic book characters like dead Pool, adult human tissues generally do not regenerate – the loss of a limb is permanent and irreversible.
Where is it?
Although there have been significant advances in prosthetic and bionic technologies to replace lost limbs, they cannot yet restore the sense of touch, minimize the feeling of phantom pains, or match the capabilities of natural limbs. Without reconstructing the limb itself, a person will not be able to feel the touch of a loved one or the warmth of the sun.
Our recent study in the journal Scientists progress showed that just 24 hours of a treatment we designed is enough to regenerate fully functional, touch-sensitive limbs in frogs.
Early in development, the cells that will eventually become limbs and organs organize themselves into specific anatomical structures using a set of chemical, biomechanical and electrical signals.
When looking at ways to regenerate limbs, we thought it would be much easier to have cells repeat what they had already done early in development. So we looked for ways to trigger the “build what was normally here” signal for cells at the site of a wound.
However, one of the main challenges is figuring out how to create an environment that encourages the body to regenerate itself instead of forming scars.
Although scars help protect injured tissue from further damage, they also alter the cellular environment in ways that prevent regeneration.
Some aquatic animals like the axolotls have mastered regeneration without scar formation. And even at the beginning of human development, the amniotic sac provides an environment that can facilitate regenerative mechanisms.
We hypothesized that developing a similar environment could undo scar formation at the time of injury and allow the body to reactivate dormant regenerative signals.
To implement this idea, we developed a wearable device consisting of a silk hydrogel as a way to create an isolated chamber for regeneration by blocking other signals that would direct the body to develop scarring or undergo other processes. We then loaded the device with a cocktail of five drugs involved in normal animal development and tissue growth.
We chose to test the device using African clawed frogs, a species commonly used in animal research that, like humans, does not regenerate limbs in adulthood.
We strapped the device to a leg stump for 24 hours. We then removed the device and observed how the site of the lost limb changed over time.
Over the course of 18 months, we were amazed to find that the frogs were able to regenerate their legs, including finger-like projections with significant regrowth of nerves, bones and blood vessels.
The limbs also responded to light pressure, meaning they regained the sense of touch and allowed the frog to resume normal swimming behavior.
Frogs that received the device but without the drug cocktail had limited limb regrowth without much functional restoration.
And frogs that weren’t treated with the device or the drug cocktail didn’t regrow their limbs, leaving stumps numb to touch and functionally impaired.
Interestingly, the limbs of frogs treated with the device and the drug cocktail were not perfectly reconstructed. For example, bones were sometimes fragmented. However, the incompleteness of the new member tells us that other key molecular signals may be missing and many aspects of treatment can still be optimized.
Once these signals are identified, adding them to drug treatment could potentially completely reverse limb loss in the future.
The future of regenerative medicine
These traumatic injuries are often caused by automobile accidents, sports injuries, side effects of metabolic diseases such as diabetes, and even battlefield injuries.
The ability to decode and reawaken dormant signals that allow the body to regenerate parts of itself is a transformative frontier of medical science.
Beyond the regrowth of lost limbs, the regeneration of heart tissue after a heart attack or brain tissue after a stroke could prolong life and significantly increase its quality. Our treatment is far from ready for use in humans, and we only know that it works when applied immediately after injury.
But discovering and understanding the signals that allow cells to regenerate means that patients may not have to wait for scientists to truly understand all the intricacies of building complex organs before they can be treated.
To make a person whole means more than simply replacing his limb. It also means restoring their sense of touch and their ability to function. New approaches in regenerative medicine are now beginning to identify how this might be possible.