Medication in the matrix

Researchers are developing scaffold-like materials designed to be injected into the body where they will quickly solidify to fit any space, repairing damaged bones, spinal cords, arteries and other tissues.

Because the material starts out as a liquid, it fills in the gaps between damaged or missing tissue before hardening into a gel, or ‘three-dimensional matrix’ that eventually disintegrates as it is replaced by healthy tissue, according to Alyssa Panitch, an associate professor in Purdue University's Weldon School of Biomedical Engineering.

This gel could be loaded with time-released therapeutic drugs, such as ‘growth factors’ needed to enhance healing. The approach also could be used to improve ‘drug-eluting stents,’ which are metal scaffolds inserted into arteries to keep them open after surgeries to treat clogs. Once in place, the stents release therapeutic agents, but scientists have recently learned that the stents can cause new clogs, leading to heart attacks.

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. The polysaccharides interact with proteins and help the proteins come together and assemble scaffolds. 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.

The technology could have several future applications, including controlled release of drugs and growth factors, which are used in wound healing, bone regeneration and other medical applications. Growth factors control cell behaviour and are used to help bone grafts integrate with surrounding bone tissue. Controlling how strongly they bind to polysaccharides could enable researchers to develop gels that, when injected, would release therapeutic peptides over months, weeks, days or hours, depending on the application.

The gels are ‘thermally reversible,’ which means heating them turns them back into a liquid.

Future research may include work to increase the gels' strength. The researchers have shown how using polymers that have more ‘functional groups’ strengthens the gels. These functional groups are segments that attach to other molecules to fortify the matrix by forming ‘crosslinks’ from one molecule to the next.

Synthetic polymers are currently used in medicine, including for 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 said.

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 said.

‘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 said. ‘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.’

The new matrix materials could be also used to make the stents used in angioplasty less prone to clot formation.