Nanomedicine for recalcitrant wounds to heal

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Injuring yourself is usually not important. The vast majority of the time we even let them heal on their own. But as we get older, changes occur that complicate the healing process. Nanotechnology can help prevent it

Injuring yourself is usually not important. The vast majority of the time we even let them heal on their own. But as we get older, our skin becomes thinner and more fragile, losing elasticity, which increases the risk of skin lesions.

In addition, over the years different pathologies such as diabetes, venous insufficiency or occlusive arterial disease appear. All of them complicate the wound healing process, slowing it down or even stopping it. That is why many normal wounds end up becoming chronic ulcers.

It has been estimated that 3.6% of people over 65 years of age have these chronic ulcers. This situation, in addition to greatly reducing the quality of life of patients, is presented as a public health problem because it generates an increase in health spending.

Dressings and other limited treatments

Various treatments are currently used to try to manage chronic wounds. Among them, dressings for moist cures stand out: alginates, hydrogels, polymeric foams, charcoal dressings, silver dressings and a long etcetera.

In general, these dressings are used to control wound exudate and, in some cases, also infections that frequently appear in this context. Its usefulness in terms of regenerative capacity is very limited.

More recently, the use of cell therapies such as the use of dermal (dermagraft) and dermo-epidermal (apligraft) substitutes has been incorporated. Again the results have been very variable and the cost too high.

Finally, the use of growth factors, substances that play a key role during the healing process, has also been explored. This is the case of EGF (epidermal growth factor) or PDGF (platelet growth factor). Its administration is in various ways to avoid its rapid degradation in the hostile (proteolytic) environment of ulcers.

However, despite the efforts made over the years in order to arrive at an acceptable therapeutic intervention in recalcitrant wounds, the success achieved in this regard has been only modest and chronic ulcers continue to be a challenge for medicine in the 21st century as well. .

That is why researchers from the Carlos III University of Madrid, the CIEMAT and the Ramón y Cajal Institute for Health Research have joined forces with the aim of designing, for the first time, aptamers capable of effectively activating the wound repair process.

Aptamers may be the solution

The project has been a success and the results were recently published in one of the world's leading scientific journals in dermatology, the Journal of Investigative Dermatology.

We explain how we generate aptamers capable of activating the healing process. These are small pieces of DNA that form unique three-dimensional structures that allow them to bind with high affinity and specificity to other target molecules.

In our case, the designed aptamers bind to a receptor, known as FPR2, located on the surface of the cells that make up the epidermis (keratinocytes), including those at the edge of the wound. This receptor is also found on the surface of other cells involved in wound healing, such as cells of the immune system and blood vessels.

For our study, we have carried out in vitro assays on cells growing in a culture plate that express the FPR2 receptor. We have also done it in vivo, using a skin-level humanized mouse model developed by our team.

In this way, we observed that the generated aptamers were highly effective in improving the wound healing response. Specifically, they are capable of specifically activating FPR2, awakening the keratinocytes so that they change their shape, from static to migratory, and begin to advance over the wound bed until it is closed. That is, the designed aptamers were able to activate the tissue repair program, a biological process that is severely hampered and impaired in patients with skin ulcers.

Aptamers have advantages over other pre-existing therapies, since they are very stable molecules, with low immunogenicity (that is, without rejection by the patient), high tissue penetration and low production cost. Therefore, we could be facing a novel and promising tool to activate the healing of ulcers that do not respond to conventional treatments.

The next step will be to complete all the preclinical studies in appropriate animal models, before moving on to clinical trials in which the safety and efficacy of the treatment in real wounds, in real patients, will be assessed.

This article has been published in 'The Conversation'.

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