To spur regrowth in a creature that does not naturally regenerate, such as an adult frog or human, researchers have experimented with stem cell implants or gene therapy. But these methods can be extremely complicated to implement, Dr. Murugan said.
An easier approach, Dr. Levin suggested, is to trigger the animal’s own body and cells to regenerate the limb.
To do this, the researchers needed to create a protected environment around the wound to inhibit scarring in the early stages of tissue repair — “to convince every cell in there that, ‘OK, we’re on the leg-growing program,’” Dr. Levin said.
They made a wearable silicone cap called the BioDome, which was filled with a silk protein hydrogel. Dr. Murugan researched all the commercially-available drugs known to encourage regeneration before settling on a mixture of five to be loaded into the BioDome and released on the wound.
In 2017, the researchers started what would become an 18-month experiment. On the first day of the experiment, a graduate student at the time, Annie Golding, and a researcher, Quang L. Pham, created the cocktail of drugs and BioDomes. Dr. Murugan — along with a technician, Kelsie Miller, and an undergraduate student, Hannah Vigran — performed 13 hours of surgery on 115 anesthetized female frogs.
For the next year and a half, the frogs ate and swam under the care of an aquaculture technician, Erin Switzer, while the researchers waited patiently.
At about the four-month mark, the frogs’ limbs began to diverge, depending on which of three experimental groups they were in, Dr. Murugan said.