A tissue section 14 days post-wounding shows hair follicles regenerating at center of the wound. Regrowing hair follicles is one of the biggest challenges in the field of wound healing. [Image from the Disease Biophysics Group/Harvard University]
Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering have created nanofiber dressings that are made of proteins that are naturally occurring in plants and animals. The proteins help promote healing and tissue regrowth.
“Our fiber-manufacturing system was developed specifically for the purpose of developing therapeutics for the wounds of war,” said Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics at SEAS and senior author of the research, in a press release. “As a soldier in Afghanistan, I witnessed horrible wounds and, at times, the healing process for those wounds was a horror unto itself. This research is a years-long effort by many people on my team to help with these problems.”
Scientists first started studying wound healing in the late 1970s. During that time, they discovered that wounds that happened before the third trimester didn’t form a scar. This meant that there were new possibilities for regenerative medicine, but researchers have since struggled to recreate the properties of fetal skin.
Fetal skin has high levels of fibronectin that collects in the extracellular matrix to promote cell binding and adhesion, according to the researchers. The fibronectin protein has two structures known as globular and fibrous. Globular structures are found in blood and fibrous are found in tissue. Fibrous fibronectin has the most potential to be used for wound healing, but other research has focused on globular striations because fibrous fibronectin was hard to engineer.
The SEAS and Wyss Institute researchers are nano fiber engineers, which meant they could make fibrous fibronectin using a fiber-manufacturing platform called the Rotary Jet Spinning (RJS) machine that works like a cotton candy machine. The researchers use a liquid globular fibronectin that has been dissolved in a solvent and load it into a reservoir in the RJS machine where it is pushed out of a tiny hole by centrifugal force as the device spins. The solvent then evaporates as it leaves the reservoir and the liquid globular fibronectin polymer solidifies. The centrifugal force the machine creates unfolds the globular protein into small, thin fibers, according tot he researchers. The fibers are less than on micrometer in diameter and are able to be made into a wound dressing or bandage.
“The dressing integrates into the wound and acts like an instructive scaffold, recruiting different stem cells that are relevant for regeneration and assisting in the healing process before being absorbed into the body,” said Christophe Chantre, a graduate student in the Disease Biophysics Group and first author of the paper.
The researchers tested the method in vivo and found that treating wounds with the fibronectin dressing showed an 84% tissue restoration in 20 days. Standard dressings had 55.6% restoration. They also showed that fibronectin-treated wounds had nearly normal epidermal thickness and dermal architecture and could regard hair follicles.
“This is an important step forward,” said Chantre. “Most work done on skin regeneration to date involves complex treatments combining scaffolds, cells, and even growth factors. Here we were able to demonstrate tissue repair and hair follicle regeneration using an entirely material approach. This has clear advantages for clinical translation.”
The researchers also tested a soy-based nanofiber that could enhance and promote wound healing. Soy protein has estrogen-like molecules that have been known to speed up wound healing as well as bioactive molecules that are similar to ones that build and support human cells.
“Both the soy- and fibronectin-fiber technologies owe their success to keen observations in reproductive medicine,” said Parker. “During a woman’s cycle, when her estrogen levels go high, a cut will heal faster. If you do a surgery on a baby still in the womb, they have scar-less wound healing. Both of these new technologies are rooted in the most fascinating of all the topics in human biology — how we reproduce.”
Soy fibers were spun until in the RJS machine until they were ultra thin and could be used as wound dressings. The soy- and cellulose-based dressings showed a 72% increase in wound healing with no dressing and 21% increase in healing in wounds dressed with no soy protein.
“These findings show the great promise of soy-based nanofibers for wound healing,” said Seungkuk Ahn, a graduate student in the Disease Biophysics Group and first author of the paper. “These one-step, cost-effective scaffolds could be the next generation of regenerative dressings and push the envelope of nanofiber technology and the wound-care market.”
The researchers suggest that the soy-based nanofibers are cheap to make, which means they could be beneficial for large-scale use. The fibronectin dressings could be used on smaller wounds on the ace and hands to prevent scarring.
The research was published in the journals Advanced healthcare Materials and Biomaterials.
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