With military conflicts continuing to rage on in many regions of the globe, understanding how tissues regenerate and heal is an area of research that has come to the forefront in recent years. Additionally, as one of the largest segments of the population move into their six and seventh decades, advanced healthcare initiatives focused on wound healing are imperative to improve quality of life and help keep seniors active. Now, investigators from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering have developed new wound dressings that dramatically accelerate healing and improve tissue regeneration.
The researchers found that naturally occurring proteins in plants and animals can promote healing and regrow tissue. Findings from the latest study—published today in Biomaterials, in an article entitled “Production-Scale Fibronectin Nanofibers Promote Wound Closure and Tissue Repair in a Dermal Mouse Model”—describes a wound dressing inspired by fetal tissue.
In the late 1970s, when scientists first started studying the wound-healing process early in development, they discovered something unexpected. Wounds incurred before the third trimester left no scars. This opened a range of possibilities for regenerative medicine. But for decades, researchers have struggled to replicate those unique properties of fetal skin
“Our fiber manufacturing system was developed specifically for the purpose of developing therapeutics for the wounds of war,” explained senior study investigator Kit Parker, Ph.D., professor of bioengineering and applied physics at SEAS and senior author of the research. “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.”
Unlike adult skin, fetal skin has elevated levels of a protein called fibronectin, which assembles into the extracellular matrix and promotes cell binding and adhesion. Fibronectin has two structures: globular, which is found in blood, and fibrous, which is found in tissue. Even though fibrous fibronectin holds the most promise for wound healing, previous research focused on the globular structure, in part because manufacturing fibrous fibronectin was a major engineering challenge.
In the current study, the researchers made fibrous fibronectin using a fiber manufacturing platform called Rotary Jet-Spinning (RJS), developed by Dr. Parker's Disease Biophysics Group. RJS works like a cotton candy machine—a liquid polymer solution, in this case, globular fibronectin dissolved in a solvent, is loaded into a reservoir and pushed out through a tiny opening by centrifugal force as the device spins. As the solution leaves the reservoir, the solvent evaporates, and the polymers solidify. The centrifugal force unfolds the globular protein into small, thin fibers. These fibers—less than one micrometer in diameter—can be collected to form a large-scale wound dressing or bandage.
“The dressing integrates into the wound and acts as an instructive scaffold, recruiting different stem cells that are relevant for regeneration and assisting in the healing process before being absorbed into the body,” noted lead study investigator Christophe Chantre, a graduate student in the Disease Biophysics Group.
Using in vivo testing, the researchers found that wounds treated with the fibronectin dressing showed 84% tissue restoration within 20 days, compared to 55.6% restoration in wounds treated with a standard dressing. Moreover, the research team also demonstrated that wounds treated with the fibronectin dressing have close to the normal epidermal thickness and dermal architecture, and even regrew hair follicles—often considered one of the biggest challenges in the field of wound healing.
“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.”
This work—combined with an additional study the research team published over the summer demonstrating that a soy-based nanofiber also enhances and promotes wound healing—increases our understanding of tissue regeneration. Soy protein contains both estrogen-like molecules, which have been shown to accelerate wound healing, and bioactive molecules similar to those that build and support human cells.
“Both the soy and fibronectin fiber technologies owe their success to keen observations in reproductive medicine,” Dr. Parker remarked. “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 new technologies are rooted in the most fascinating of all the topics in human biology—how we reproduce.”
Both kinds of dressing, according to researchers, have advantages in the wound-healing space. The soy-based nanofibers—consisting of cellulose acetate and soy protein hydrolysate—are inexpensive, making them a good option for large-scale usages, such as on burns. The fibronectin dressings, on the other hand, could be used for smaller wounds on the face and hands, where the prevention of scarring is important.