Utilizing exosomes and hydrogels to promote diabetic wound healing

Diabetes is a widespread disease that affects approximately 13% of American adults and is often associated with complications such as impaired wound healing that, if left untreated, can lead to serious consequences, including the need for amputation.

The challenge of finding effective treatments for diabetic wounds is becoming increasingly urgent. Diabetic wounds are characterized by prolonged inflammation, oxygen deficiency, and impaired angiogenesis, all of which contribute to delayed healing. However, new frontiers in biomedical research are showing that exosomes may be a potential solution.

A team from NYU Langone and NYU Tandon, including Jin Kim Montclair, has begun investigating exosomes, tiny membrane-bound vesicles, as a potential therapeutic tool. These nanovesicles can carry a variety of biological materials, including nucleic acids, proteins, and lipids, mediate communication between cells, and affect processes such as tissue repair.

The findings are published in ACS Applied Bio Materials.

Specifically, exosomes derived from mesenchymal stem cells (MSCs), including those derived from adipose tissue, have demonstrated great potential to promote wound healing in animal models. Their therapeutic benefits appear to stem from their ability to reduce inflammation and promote a favorable environment for healing by promoting angiogenesis and enhancing the activity of cells such as fibroblasts and endothelial cells that are essential for tissue repair.

One major advantage of exosomes is that they avoid some of the risks associated with traditional stem cell therapies, such as uncontrolled cell proliferation and immune rejection. However, despite their promise, exosomes typically require repeated administration via subcutaneous or intravenous injections, and long-term wound management presents challenges.

The Montclair team is exploring innovative ways to enhance the therapeutic effects of exosomes, one of which is combining them with hydrogels, which consist of a network of cross-linked polymers that can encapsulate exosomes within their structure. This encapsulation allows for a more sustained and localized release of exosomes directly to the wound site, without the need for invasive injections.

Hydrogels are already useful as wound dressings due to their biocompatibility and ability to hydrate wounds, but when combined with exosomes, their therapeutic efficacy is greatly enhanced, especially for diabetic wounds.

Recent studies have shown that the combination of hydrogel and exosomes consistently results in faster wound closure than either hydrogel or exosomes alone. Although these hydrogel systems are not protein-based, recent advances in protein-based hydrogel technology have opened new possibilities for improving wound healing.

Montclair has developed a protein-based hydrogel called “Q,” which forms a gel at low temperatures through a process called upper critical solution temperature (UCST) gelation. This protein-based hydrogel self-assembles into nanofibers, forming a physically cross-linked network that provides mechanical strength.

By fine-tuning the protein sequence using advanced computational tools such as Rosetta score and Poisson-Boltzmann electrostatic potential calculations, they were able to improve the mechanical properties, stability and rate of formation of the gel – key factors for creating an ideal wound dressing.

To further this approach, the researchers engineered a variant of Q hydrogel, called Q5, and employed automated selection methods to optimize its stability. They encapsulated exosomes within Q5 to create a novel hydrogel-exosome system, called Q5Exo, which provides a topical, non-invasive wound dressing that can treat diabetic wounds more effectively than traditional methods that rely on injections.

A study using a diabetic mouse model demonstrated that Q5Exo significantly reduced healing times when applied topically compared to exosomes administered via injection, suggesting that protein-based hydrogels with tunable properties may be a powerful platform to improve wound healing outcomes in diabetes.

As research progresses, such hydrogels may pave the way for a new generation of biocompatible and efficient wound dressings that harness the therapeutic properties of exosomes.