Alyssa Panitch, an associate professor in Purdue's Weldon School of Biomedical Engineering, holds a sample of a scaffoldlike material designed to be injected into the body, where it would quickly solidify to fit any space, repairing damaged bones, spinal cords, arteries and other tissues. (Photo by Vincent Walter)

The material starts out as a liquid, fills in the gaps between damaged or missing tissue then hardens into a gel, or "three-dimensional matrix" that eventually disintegrates as it is replaced by healthy tissue, explains Alyssa Panitch, an associate professor in Purdue University's Weldon School of Biomedical Engineering.

The method harnesses natural interactions in the body between molecules called polysaccharides and protein building blocks called peptides to control the assembly of the three-dimensional matrices. Researchers have used the interaction between a polysaccharide called heparin and a peptide fragment of a protein called antithrombin III, which is contained in the bloodstream to control clotting.

"But we could have chosen peptides from many other proteins instead of antithrombin III and also different polysaccharides to tailor our matrix for specific applications," Panitch says.

The proteins exist in the "extracellular matrix" located between tissue cells. The researchers attached heparin-binding peptides from antithrombin III to a synthetic material called polyethylene glycol. Mixing solutions of this peptide-polyethylene glycol combination with heparin instantly produces a three-dimensional matrix. "It's a very rapid assembly and the matrix can take any shape," says Panitch, who specializes in regenerative medicine.

The technology could have several future applications, including controlled release of drugs and growth factors used in wound healing and bone regeneration. Growth factors control cell behavior and are used to help bone grafts integrate with surrounding bone tissue. Controlling how strongly they bind to polysaccharides could lead to gels that release therapeutic peptides over months, weeks, days, or hours. The gels are also thermally reversible. Heating them turns them back into a liquid. This could be important for controlled release for drug therapy, contends Panitch. "If you wanted to locally heat up the tissue to make the release faster, you could do that."

Synthetic polymers are currently used in medicine, including sutures that degrade over time and wound-repair dressings. But using peptides derived from natural proteins promises further advances in the field of tissue engineering because the researchers can tweak the materials by changing the sequence of amino acids in matrix peptides, Panitch says.

Such scaffolds might be used to repair damaged arteries by mimicking the natural matrices that surround smooth muscle cells in vessel walls. One application likely to emerge over the next decade is a material to treat spinal cord injuries, Panitch says. "It is thought that most of the damage caused in spinal cord injury is not caused by the initial injury but by the inflammation that occurs later," she says. "So, if you could inject this gel with a therapeutic agent that inhibits inflammation while secreting growth factors within several hours of injury, that could potentially be very useful."

New matrix materials could also have likely applications in other "drug-eluting" materials that release therapeutic agents inside the body, including a type of stent used to keep arteries open after surgeries.



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