Why Do Diabetic Wounds Take Longer to Heal? A Breakthrough Study Explains

Diabetic patients often grapple with delayed wound healing, with some wounds even becoming chronic. In extreme cases, these non-healing wounds can lead to the drastic measure of amputation. The precise reason behind this delay has remained an enigma for many years, but recent research has finally illuminated a significant contributing factor.

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keratinocyte Macrophages Crosstalk Via Exosomes

keratinocyte Macrophages Crosstalk Via Exosomes. Credit: Mohamed S. El Masry

In a breakthrough study published in Nano Today, a research team from the University of Pittsburgh has unearthed the crucial role played by tiny particles called exosomes. These particles act as couriers, shuttling information between cells. Yet, in diabetic patients, these exosomes are found to be defective.

Deciphering the Exosome Puzzle

In healthy individuals, exosomes ferry essential information to cells, ensuring that the wound-healing process unfolds normally. Dr. Subhadip Ghatak, the lead author and an associate professor of surgery at the university, highlighted that in diabetic patients, these defective exosomes may instigate inflammation. This, in turn, can hamper or outright stall the wound-healing process. When chronic wounds emerge in diabetics, it’s these malfunctioning exosomes that are unable to convey the crucial information cells need to facilitate healing.

The Study’s Insights

The research encompassed the collection of wound exudate, which is a snapshot of everything happening within the wound, from 22 diabetic and 15 non-diabetic patients. This exudate was obtained using a negative pressure therapy technique, which gently draws out excess exudate and simultaneously encourages healing.

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A closer analysis revealed markers that, when present in exosomes, guide immune cells (macrophages) on how to counter wound inflammation. However, in diabetics, the communication between skin cells (keratinocytes) and macrophages is muddled. This means macrophages persist in instigating inflammation, preventing the wound from healing.

These diabetic exosomes, coined “diaexosomes” by the researchers, were found to have vastly different concentrations of RNA, lipids, and proteins than their non-diabetic counterparts. This indicates that exosome conditioning processes are impaired in diabetics. Furthermore, the release and absorption of exosomes into wounds are also hindered in diabetes, with diaexosomes in the wound exudate of diabetic patients being markedly lower than in non-diabetics. When exposed to these diaexosomes, macrophages produce compounds common in diabetics that exacerbate inflammation and the chronic nature of the wound.

Beyond the Wound: Implications and Treatment Outlook

Interestingly, the influence of these diaexosomes isn’t restricted to wounds alone. Given their myriad functions within the body, they might also negatively impact other diabetic complications.

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Recognizing the devastating impact of these malfunctioning diaexosomes, the team is pioneering new therapies to negate their harmful effects. One proposed strategy is to inhibit the chemical alterations that occur within diaexosomes. Another promising therapeutic avenue being explored is isolating “healthy” exosomes from diabetic patients, replenishing them with any missing agents, and then reintroducing them into the wound bed.

This research not only sheds light on a previously uncharted aspect of diabetic wound healing but also paves the way for transformative treatments that could potentially save limbs and lives.

References

Street, J.M. (2023). Nanoscopic and functional characterization of keratinocyte-originating exosomes in the wound fluid of non-diabetic and diabetic chronic wound patients. Retrieved from https://doi.org/10.1016/j.nantod.2023.101954

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