Smart Hydrogel Degrades When New Bone Grows

Bioengineers have created a hydrogel to help people regrow lost bone and tissue. The material is liquid at room temperature but turns semisolid when it’s injected into a patient.

It’s built to degrade as bone and tissue seeded from the patient’s cells grow to take it’s place.

A problem with thermogelling polymers is that once they harden, they begin to collapse and then force out water, says Brendan Watson, a graduate student at Rice University who helped create the hydrogel.

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

Long-term Stability

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.

“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. Then the defect-filling goal is no longer accomplished,” Watson says.

Watson and 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 stabilize the gel,” he says.

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

Semi-smart Material

Watson, who is pursuing both a Rice doctorate and a medical degree in a joint program with nearby Baylor College of Medicine, explains:

“I came up with the idea a few years ago, but it’s finally all come together. 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.

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 says. “So what we get is a semi-smart 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.”

Watson expects that the material degradation can be tuned to match various bone growth rates.

“Optimizing the degradation kinetics is nontrivial and may be better suited for a biotech company,” Watson adds. “We focus more on the performance of the hydrogels and the underlying molecular mechanisms”

Brendan M. Watson, F. Kurtis Kasper, Paul S. Engel, and Antonios G. Mikos
Synthesis and Characterization of Injectable, Biodegradable, Phosphate-Containing, Chemically Cross-Linkable, Thermoresponsive Macromers for Bone Tissue Engineering
Biomacromolecules 2014 15 (5), 1788-1796 DOI: 10.1021/bm500175e

Photo: Wellcome Images