Now, hydrogel that degrades as new bone tissue forms

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Washington: Researchers have created a hydrogel which can be injected into patients to induce bone regeneration and quickly degrades when new tissue forms and matures.

The gel, developed by Rice University, is liquid at room temperature but, when injected into a patient, becomes a gel that would fill and stabilise a space while natural tissue grows to replace it.

The gel shows potential as a bioscaffold to support the regrowth of bone and other three-dimensional tissues in a patient's body using the patient's own cells to seed the process, researchers said.

"This study describes the development of a novel thermogelling hydrogel for stem cell delivery that can be injected into skeletal defects to induce bone regeneration and that can be degraded and eliminated from the body as new bone tissue forms and matures," said Antonios Mikos, Rice's Louis Calder Professor of Bioengineering and Chemical and Biomolecular Engineering.

A problem with thermogelling polymers is that once they harden, they begin to collapse and then force out water, said Rice graduate student and the study's lead author, Brendan Watson.

That process, known as syneresis, defeats the purpose of defining the space doctors hope to fill with new tissue.

"If the transition gellation temperature is one or two degrees below body temperature, these polymers slowly start to expel water and shrink down until they're one-half or one-third the size," Watson said.

"Then the defect-filling goal is no longer accomplished," he said.

Watson and his colleagues solved the problem by adding chemical cross-linkers to the gel's molecules.

"It's a secondary mechanism that, after the initial thermogellation, begins to stabilise the gel," he said.

The links begin to form at the same time as the gel, but crosslinking takes up to a half-hour to complete.

The hydrogel is designed for stability over its long-term use as a scaffold for cells to take root and proliferate. But it's also designed for its own timely destruction.

"These chemical crosslinks are attached by phosphate ester bonds, which can be degraded by catalysts - in particular, alkaline phosphatase - that are naturally produced by bone tissue," Watson said.

"The catalysts are naturally present in your body at all times, in low levels. But in areas of newly formed bone, they actually get to much higher levels," he said.

"So what we get is a semismart material for bone-tissue engineering. As new bone is formed, the gel should degrade more quickly in that area to allow even more space for bone to form," he added.



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