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Genetic Acids Harnessed to Promote Wound Healing

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8 Jan. 2019. A bioengineering team designed a way to use acids in DNA that in lab tests promote wound repair by encouraging production of healing proteins in surrounding tissues. Researchers from Imperial College London in the U.K. describe their process in yesterday’s issue of the journal Advanced Materials.

Researchers led by Imperial College engineering lecturer Ben Almquist are seeking new methods for healing wounds without creating entirely new medical technologies. Recent advances in regenerative medicine use three-dimensional materials such as hydrogels and scaffolds to promote repair of chronic wounds, such as diabetic foot ulcers, or acute traumatic injuries. These techniques often require the healing materials to bind with adjacent tissue, or in some cases need external triggers, such as light activation. While these techniques may get results in the lab, say the authors, they have less success in the more complex animal or human tissue environment.

Almquist and colleagues designed a strategy that promotes the natural production of growth factor proteins when combined with these tissue-repair technologies. The team seeks to emulate the protein called transforming growth factor or TGF-beta, which remains in an inactive state, inside a protein structure known as the large latent complex. When confronted by a wound, signals from the damaged tissue cells break through the large latent complex to release TGF-beta. Not only does TGF-beta directly encourage wound repair, it encourages other neighboring cells to send similar signals for TGF-beta to support the healing process.

The researchers also seek simple solutions that work with a wide range of healing technologies. The focused on aptamers, nucleic acids related to DNA and RNA that bind to proteins. The Imperial College team synthesized molecules with aptamers, folded and connected to a peptide that attaches to cells, which also can integrate with a variety of substances used in wound healing. They call their nanoscale synthesized molecules traction force-activated payloads, or Traps.

In lab tests, the researchers found Traps work similarly to TGF-beta, which when exposed to signals from damaged tissue cells, are released into the wound region. The lab results show release of Traps triggers production of other healing proteins including platelet?derived growth factor?BB that stimulates stem cells for regenerating skin and muscle tissue, and vascular endothelial growth factor or VEGF-165 that promotes blood vessel development. The researchers also found Traps could integrate with a variety of materials used in regenerative medicine, including collagen scaffolds and sponges, water-polymer hydrogels, and glass surfaces.

Because aptamers, the core of the Traps system, are already used in a number of current therapies, the team believes it could receive faster regulatory approval than an entirely new technology. “Traps,” says Almquist in an Imperial College statement, “provide a flexible method of actively communicating with wounds, as well as key instructions when and where they are needed. This intelligent healing is useful during every phase of the healing process, has the potential to increase the body’s chance to recover, and has far-reaching uses on many different types of wounds.”

Imperial College London applied for a patent on the technology, with Almquist and first author Anna Stejskalová as inventors. The following video tells more about Traps.

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