New study shows how PAINTing with wound-healing ink can promote quick recovery

Now a team of scientists from the Nanjing University of Posts and Telecommunications, Chinese Academy of Sciences, Nanjing University in China, and the Agency for Science, Technology and Research A*STAR in Singapore have created a wound healing ink that actively promotes the body's ability to heal by exposing the wound to immune-system vesicles.

How does the body promote wound healing?

The body's natural wound healing system or construction crew kicks in when the skin is wounded. The entire wound-healing process is very complex and well-coordinated. 

When a wound occurs, the body initiates hemostasis, which is the process that stops bleeding. Blood vessels in the area restrict blood flow, following which platelets activate and aggregate at the site to form a blood clot and seal the wound.

After this, the inflammatory process begins where the white blood cells, which are part of the body's immune system, remove debris and fight infection. Now that the wound is protected, the body begins the proliferation phase. 

In this phase, new tissue and blood vessels start to form, and the wound starts closing up. Following this, remodeling takes place to refine and strengthen the healed tissue. 

Throughout the healing process, various growth factors, cytokines, and signaling molecules are released, regulating cell behavior, promoting tissue repair, and modulating inflammation. Adequate nutrition, oxygen supply, and a healthy immune system are crucial for optimal wound healing.

PAINT: Portable bioactive ink for tissue healing

EVs have shown promising potential in aiding wound healing processes. They can be released by various cell types involved in wound healing, such as immune cells, fibroblasts, and endothelial cells.

Given their promise, the research team decided to incorporate EVs into a hydrogel-based wound-healing ink that can be painted onto a wound of any shape.

The ink called PAINT, or portable bioactive ink for tissue healing, was developed from EVs secreted by macrophages. Macrophages are a type of immune cell that engulf and digest cellular debris, pathogens, and foreign substances in the body. 

The EVs were combined with sodium alginate, which is commonly used to create gels or dressings that provide a moist environment, facilitate healing, and promote tissue regeneration, in a 3D-printing pen. They mixed the components at the pen's tip, forming a sturdy gel at the wound site within three minutes. 

The EVs accelerated the process by promoting blood vessel formation and reducing inflammatory markers in human epithelial cells (present in the outermost layer of our skin), moving them to the proliferation state. 

To test their technology, researchers used PAINT on injured mice. They found that PAINT promoted collagen fiber in injured mice. Additionally, large wounds were almost completely healed in 12 days.

According to a press release, the researchers think that the PAINT technology can help to heal a wide variety of wounds quickly and easily without any complex procedures.

The findings were published in the journal ACS Applied Materials & Interfaces.

Study abstract:

The treatment of cutaneous wounds involving complex biological processes has become a significant public health concern worldwide. Here, we developed an efficient extracellular vesicle (EV) ink to regulate the inflammatory microenvironment and promote vascular regeneration for wound healing. The technology, termed portable bioactive ink for tissue healing (PAINT), leverages bioactive M2 macrophage-derived EVs (EV_M2) and a sodium alginate precursor, forming a biocompatible EV-Gel within 3 min after mixing, enabling it to be smeared on wounds in situ to meet diverse morphologies. The bioactive EV_M2 reprogram macrophage polarization and promote the proliferation and migration of endothelial cells, thereby effectively regulating inflammation and enhancing angiogenesis in wounds. Through integration with a 3D printing pen, the platform enables EV-Gel to be applied to wound sites having arbitrary shapes and sizes with geometric matches for tissue repairment. When evaluated using a mouse wound model, PAINT technology accelerates cutaneous wound healing by promoting the angiogenesis of endothelial cells and the polarization of macrophages to M2 phenotype in vivo, demonstrating the high potential of bioactive EV ink as a portable biomedical platform for healthcare.