Researchers have genetically engineered maggots so they help wound healing by doing more than eat dead flesh and kill microbes. The modified fly larvae also produce and release a hormone – a human growth factor – that actively stimulates cell growth and wound healing.

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The researchers genetically engineered green bottle fly larvae to produce and secrete a human growth factor in response to a trigger.
Image credit: Max Scott

Maggot debridement therapy (MDT) is an approved treatment that is shown to be cost-effective for the treatment of diabetic foot ulcers. It has also been used successfully to treat many other medical conditions, note the researchers, who write about their work in the journal BMC Biotechnology.

In MDT, sterile, lab-raised larvae of the green bottle fly Lucilia sericata are applied to stubborn wounds that are failing to heal, such as diabetic foot ulcers. The maggots clean the wound by removing dead tissue and disinfecting the area through the release of antimicrobial compounds.

However, note the authors, there is no evidence, from randomized clinical trials, that MDT – which is approved by the Food and Drug Administration (FDA) – shortens the time it takes for wounds to heal.

For that to happen, the maggots would have to do more than clean the wound; they would have to actively speed up the healing process. The researchers wondered if one way to do this was to engineer maggots that stimulate the growth of new, healthy cells.

As such, the team – from North Carolina State University (NCSU) in Raleigh and Massey University in New Zealand – decided to see if they could make a strain of maggot that releases a human growth factor that actively stimulates cell growth and survival.

In their paper, the researchers describe how they genetically engineered green bottle fly larvae to produce and secrete human platelet-derived growth factor-BB (PDGF-BB) in response to a trigger.

PDGF-BB stimulates cell growth and survival, promotes wound healing and has been investigated as a possible topical treatment for non-healing wounds, note the authors.

The researchers tried two ways to make genetically engineered maggots that produce and secrete PDGF-BB. First, they engineered maggots that produce the human hormone when they are shocked with heat up to 37°C. But they found while heat made the maggots produce PDGF-BB, they did not release it.

Max Scott, professor of entomology at NCSU, says while it is helpful to know that you can use heat to get green bottle fly larvae to produce certain proteins, it is a “non-starter for clinical applications like MDT.”

The second try was more successful and showed more potential for clinical use. The team engineered the maggots so they only made PDGF-BB if raised on a diet that lacked the antibiotic tetracycline. The insects produced high levels of the growth factor, and it was also present in their excretions and secretions.

The authors note that most people with diabetes live in less wealthy countries with little access to expensive treatments, and MDT could offer them an effective and accessible alternative. Prof. Scott concludes:

We see this as a proof-of-principle study for the future development of engineered L. sericata strains that express a variety of growth factors and antimicrobial peptides with the long-term aim of developing a cost-effective means for wound treatment that could save people from amputation and other harmful effects of diabetes.”

In March 2015, Medical News Today learned how another team is developing a way to promote wound healing using nanoparticles that help healing cells travel faster to the injury site.