Hydrogels hold hope for healing

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 potential uses for a new biomaterial invented by UD scientists.

The novel material, which has surprising antibacterial properties, can be injected as a low-viscosity gel into a wound, where it becomes rigid nearly on contact. That feature opens the door to the possibility of delivering a targeted payload of cells and antibiotics to repair the damaged tissue.

The patented invention by Joel Schneider, 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.

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. Such potential uses include 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 says.

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 says. “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, producing 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.

The peptide-based hydrogels developed by the UD researchers 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. The research team currently is exploring this antimicrobial characteristic.

These 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.

Collaborations with physicians at Christiana Care Health System in Newark, Del., may lead to future developments for the hydrogels.

Both Schneider and Pochan attribute this new collaboration to the Center for Translational Cancer Research, a collaboration of Christiana Care Health System, A.I. du Pont Hospital for Children and UD, including the University’s Delaware Biotechnology Institute. The translational research center is directed by Mary C. Farach-Carson, a professor of both biological sciences and materials science at the University.

“For the research I was working on when I was a graduate student a long time ago, the last thing I wanted to make was hydrogels,” Schneider says, “so when that’s what I ended up with, I’d throw them out. Then Darrin said to me, ‘You know, these things are really pretty interesting.’”

Schneider and Pochan’s most recent hydrogel study is reported in the May 8 (print) edition of the Proceedings of the National Academy of Sciences. Their research is funded by the National Science Foundation and the National Institutes of Health.

—Tracey Bryant