Credit: Disease Biophysics Group/Harvard University
Developed by researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering, the two nanofibre dressings use naturally-occurring proteins in plants and animals to promote healing and regrow tissue. The breakthroughs are described in separate papers.
"Our fibre 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. "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."
The most recent paper, published in Biomaterials, describes a wound dressing inspired by foetal tissue.
In the late 1970s, when scientists first started studying the wound healing process early in development, they discovered that wounds incurred before the third trimester left no scars. This opened a range of possibilities for regenerative medicine but researchers have struggled to replicate those properties of foetal skin.
Foetal skin has high levels of fibronectin, a protein that 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.
The researchers made fibrous fibronectin using Rotary Jet-Spinning (RJS), developed by Parker's Disease Biophysics Group. With RJS a liquid polymer solution - globular fibronectin dissolved in a solvent - is loaded into a reservoir and pushed out through an 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 fibres. These fibres - less than one micrometre in diameter - can be collected to form a large-scale 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.
In in vivo testing, the researchers found that wounds treated with the fibronectin dressing showed 84 per cent tissue restoration within 20 days, compared to 55.6 per cent restoration in wounds treated with a standard dressing.
The researchers also demonstrated that wounds treated with the fibronectin dressing have close to normal epidermal thickness and dermal architecture, and even regrew hair follicles.
"Most work done on skin regeneration to date involves complex treatments combining scaffolds, cells and even growth factors,” said Chantre. “Here we were able to demonstrate tissue repair and hair follicle regeneration using an entirely material approach. This has clear advantages for clinical translation."
In another paper published in Advanced Healthcare Materials, the Disease Biophysics Group demonstrated soy-based nanofibres that enhance and promote wound healing.
Soy protein contains oestrogen-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 fibre technologies owe their success to keen observations in reproductive medicine," said Parker. "During a woman's cycle, when her oestrogen 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.”
In a similar way to fibronectin fibres, the research team used RJS to spin ultra-thin soy fibres into wound dressings. In experiments, the soy and cellulose-based dressing demonstrated a 72 per cent increase in healing over wounds with no dressing and a 21 per cent increase in healing over wounds dressed without soy protein.
According to the researchers, both kind dressings have advantages in the wound-healing space. The soy-based nanofibres - consisting of cellulose acetate and soy protein hydrolysate - are inexpensive, making them a good option for large-scale usage, such as on burns. The fibronectin dressings could be used for smaller wounds where the prevention of scarring is important.