Bioadhesive patches: harnessing the power of extracellular vesicles for enhanced healing

Surgical procedures often rely on sutures and staples to close wounds and incisions, but these methods can sometimes fall short, especially when it comes to delicate or irregular tissues. Imagine a material that could instantly adhere to tissues, stretch significantly without breaking, and even deliver therapeutic substances directly to the site. This is exactly what a team of researchers at the University of North Carolina at Chapel Hill has developed—a next-generation bioadhesive patch that promises to revolutionize the way we approach surgical wound closure and healing, with a special focus on the use of extracellular vesicles (EVs).

The Problem with Traditional Methods

Traditional methods like sutures and staples, while effective, have several drawbacks. They can cause additional trauma to the tissue, lead to scarring, and sometimes don’t provide the flexibility needed for certain types of wounds. Moreover, they can be time-consuming to apply and often require follow-up procedures for removal, which can cause further pain and bleeding.

Introducing the New Bioadhesive Patch

The researchers have created a bioadhesive patch that overcomes these limitations.

  1. Instant Adhesion: This patch adheres to tissues instantly and is 2.5 times stronger than Tisseel, a commonly used FDA-approved fibrin glue. This means it can securely hold tissues together immediately upon application.
  2. Ultra-Stretchability: The patch can stretch to more than 300% of its original length without losing its elasticity. This is crucial for tissues that need to move or expand, such as skin or lung tissue.
  3. Rapid Fabrication: Using a technique called rapid photo-projection, these patches can be fabricated in less than two minutes. This makes them highly practical for use in emergency and surgical settings.
  4. Therapeutic Delivery with Extracellular Vesicles: One of the most groundbreaking aspects of these patches is their ability to deliver therapeutic substances, specifically extracellular vesicles (EVs) derived from mesenchymal stem cells. EVs are nano-sized particles that naturally carry proteins, lipids, and genetic material between cells, playing a critical role in intercellular communication and tissue repair.

The Role of Extracellular Vesicles

Extracellular vesicles are at the forefront of this innovation. These tiny particles have shown immense potential in promoting healing and reducing inflammation. The bioadhesive patches are coated with EVs, which can enhance the natural healing processes of the body. Here’s how they work:

  • Promotion of Wound Healing: EVs have been shown to promote cell proliferation and differentiation, key processes in tissue regeneration. When applied to a wound, they can accelerate the repair of damaged tissues.
  • Anti-Inflammatory Properties: EVs can modulate the immune response, reducing inflammation at the wound site. This helps in minimizing scarring and improving the overall healing process.
  • Non-Immunogenic: Unlike some other treatments, EVs do not provoke a foreign body response, making them safe for use without the risk of adverse reactions.

In Vivo Success

In live animal tests, the patches demonstrated impressive wound healing capabilities. They helped wounds heal robustly without triggering a foreign body response. Moreover, unlike traditional sutures or staples, these patches do not need to be removed, which avoids causing additional pain or bleeding.

A Specific Application: Lung Puncture Wounds

One of the most exciting applications of this new technology is in treating lung puncture wounds. The researchers developed a specific type of patch that can fill voids in lung tissue and seal punctures effectively. This could be a significant advancement in treating traumatic injuries to the lungs, which are typically challenging to manage with traditional methods.

AuxES patches loaded with CNP and MSC-EVs upregulate genes associated with
proliferative and remodeling stages of wound healing

Fig. 7

A Heatmap depicting expression changes normalized to the no-patch treatment group, with expression levels equaling No Patch colored white. Upregulated genes are depicted in dark blue, down-regulated genes highlighted in yellow. Zoomed in heatmap from panel (a) highlighting the genes annotated as mediators in the proliferative or remodeling phases of wound healing. Identical color scale to larger heatmap. Data are from n = 3 biologically independent samples per group and are presented as gene fold change over no treatment group. B Volcano plot of differential gene expression, with the black points indicating the AuxES patch without CNPs compared to the No Treatment-patch group, and red as AuxES patch with both CNPs and MSC-EVs compared to no patch. The Y-axis is the negative log10 of the p-value as calculated with multiple two tail t-tests for each gene. The X-axis is the log2 fold-change in expression of a given gene. Variance assumptions assumed individual variances for each row, and multiple comparisons were tabulated using False Discovery Rate (FDR), and the two-stage step up method (Benjamini, Krieger, and Yekutieli) with desired Q of 1.00%. C Gene ontology (GO) biological process pathways expressed as fold enrichment as compared to mus musculus gene list. D Reactome pathway analysis depicted with the -LOG of the entity’s ratio, or the ratio of genes provided vs the total pathway components.

Conclusion

This new bioadhesive patch, enhanced with extracellular vesicles, represents a significant leap forward in surgical technology. By combining instant adhesion, ultra-stretchability, rapid fabrication, and the powerful therapeutic properties of EVs, it addresses many of the limitations of current surgical materials. This innovation not only improves the efficiency of surgical procedures but also enhances patient outcomes by promoting faster and more robust healing.

As this technology continues to develop, it holds the promise of transforming how we approach wound care and surgical repairs, making surgeries safer, faster, and more effective. The future of surgery is looking brighter with the advent of these next-generation bioadhesive patches, particularly their integration of extracellular vesicles for superior healing capabilities.

Chansoria P, Chaudhari A, Etter EL, Bonacquisti EE, Heavey MK, Le J, Maruthamuthu MK, Kussatz CC, Blackwell J, Jasiewicz NE, Sellers RS, Maile R, Wallet SM, Egan TM, Nguyen J. (2024) Instantly adhesive and ultra-elastic patches for dynamic organ and wound repair. Nat Commun 15(1):4720. [article]

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