University of Delaware scientists have invented a novel biomaterial with surprising antibacterial properties that can be injected as a low-viscosity gel into a wound where it rigidifies nearly on contact--opening the door to the possibility of delivering a targeted payload of cells and antibiotics to repair the damaged tissue.

Regenerating healthy tissue in a cancer-ridden liver, healing a biopsy site and providing wounded soldiers in battle with pain-killing, infection-fighting medical treatment are among the myriad uses the scientists foresee for the new technology.

The patented invention by Joel Schneider, UD associate professor of chemistry and biochemistry, and Darrin Pochan, associate professor of materials science, and their research groups marks a major step forward in the development of hydrogels for medical applications.

Close-up of University of Delaware hydrogel. Credit: Kathy F. Atkinson/University of Delaware

Formulating hydrogels as delivery vehicles for cells extends the uses of these biopolymers far beyond soft-contact lenses into an intriguing realm once viewed as the domain of science fiction, including growing bones and organs to replace those that are diseased or injured.

“This is an area that will be exploding over the next decade,” Pochan said.

Hydrogels are formed from networks of super-absorbent, chain-like polymers. Although they are not soluble in water, they soak up large amounts of it, and their porous structure allows nutrients and cell wastes to pass right through them.

Schneider and Pochan and their research teams have been focusing on developing peptide-based hydrogels that, once implanted in the human body, will become scaffolds for cells to hold onto and grow--cells such as fibroblasts, which form connective tissue, and osteoblasts, which form bone.

“They're like rebar when you're building something with concrete,” Schneider said. “They give the cement something to hang onto.”

The basis of UD's hydrogels is “MAX1,” a self-assembling peptide that the scientists designed six years ago and named after Pochan's son, Max.

Peptides are short chains of amino acids, the building blocks of proteins. Different amino acids are bonded together to form chains, which then fold up into more compact shapes with specific functions.

The peptide that Schneider and Pochan and their research teams designed undergoes triggered “self-assembly,” meaning that the peptide will fold automatically into a specific shape in response to a particular trigger, or environmental stimulus, such as exposure to light. After folding, it self-assembles, affording the hydrogel.

Using “MAX8,” the eighth iteration of their original peptide, Lisa Haines-Butterick, a doctoral student in Schneider's group, figured out how to encapsulate living cells in the hydrogel and then inject the gel into secondary sites without harming the cells.

“Although we have currently only demonstrated this capacity of our gels using simple models, we envision that when injected into the body, the cells encapsulated in the gel can go about their business in restructuring the tissue,” Schneider explained.

UD's peptide-based hydrogels display several novel features. Not only are they cytocompatible, meaning that they are not toxic to the living cells they are enlisted to deliver, but some of the gels are inherently antimicrobial, killing certain gram-negative and gram-positive bacteria, a characteristic the research team currently is exploring.

The UD hydrogels also can be freeze-dried into a powder and reconstituted into a solution for use. They can be injected from a syringe, offering a minimally invasive approach to medical treatment, as well as a targeted, “leak-proof' way of potentially delivering cells and drugs to a wound or diseased organ.

Mouse fibroblasts (cells that form connective tissue) on the surface of the University of Delaware's hydrogel. The hydrogel provides a “scaffold” for the tissue cells to hold onto and grow. Photo courtesy of Joel Schneider. Credit: Joel Schneider/University of Delaware

Collaborations with physicians at Christiana Care Health System in Newark, Del., may lead to future developments for the hydrogels. Schneider recently began working with Dr. Joseph Bennett, a surgeon at the Helen F. Graham Cancer Center who resects liver tumors.

Both Schneider and Pochan attribute this new collaboration to the Center for Translational Cancer Research, a collaboration of Christiana Care Health System, A. I. duPont Hospital for Children and UD, including the University's Delaware Biotechnology Institute. The center is under the direction of Mary C. Farach-Carson a professor of both biological sciences and material sciences at UD.

“You know, the liver is an amazing organ,” Schneider said. “It has the ability to regenerate itself quite easily. If almost 70 percent of it is lost to disease and removed, that remaining 30 percent can grow back, affording a functional liver. We want to use the hydrogels to deliver hepatocytes to the liver,” he noted. “These could be used to beef up the liver's function prior to surgery if, for example, someone had hepatitis, or drank a lot, factors that would normally limit the amount of cancerous liver that can be removed.”

Source: University of Delaware