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Hydrogel scaffold for new bone growth degrades when no longer needed
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A new hydrogel developed by bioengineers in Rice University in Texas has potential as a bioscaffold for fresh bone growth or other three-dimensional tissues from a patient’s stem cells. The major advantages of this hydrogel are that it turns instantly from solid to liquid at close to body temperature, meaning it readily fills and stabilises a space upon injection, and that it degrades in response to enzymes produced by newly growing bone. The results of the study are published in the American Chemical Society journal Biomacromolecules.

The new hydrogel overcomes problems associated with other thermogelling polymers in terms of tendency to collapse and expel water upon hardening. This process, termed syneresis, prevents the gel being able to fill the space where the new tissue is to be seeded. The research team addressed this issue by introducing chemical cross-linkers to the gel’s molecules. First author Brendan Watson, from the lab of Dr Antonios Mikos, explains: “It’s a secondary mechanism that, after the initial thermogellation, begins to stabilize the gel.” The crosslinking begins at the same time as the gel formation, but takes up to a half-hour to complete.

The hydrogel is designed to be stable over the long-term to allow the stem cells to establish themselves and begin proliferating to give new bone. However at this point, when the need for the scaffold declines, the hydrogel is degraded in a timely fashion. Brendan Watson explains the elegant mechanism of timed degradation: “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.”

The hydrogel represents the culmination of years of painstaking work in refining its’ properties from the research team which included input from Paul Engel, chair of Rice’s Department of Chemistry, and F. Kurtis Kasper, a senior faculty fellow in bioengineering. The expectation is that the degradation kinetics can be further fine-tuned in order to match various bone growth rates, with input from biotechnology companies. Brendan Watson concludes: “Optimizing the degradation kinetics is nontrivial and may be better suited for a biotech company…We focus more on the performance of the hydrogels and the underlying molecular mechanisms."

Sources

Watson, B.W., Kasper, F.K., Engel, P.S. and Mikos, A.G. (2014). Synthesis and Characterization of Injectable, Biodegradable, Phosphate-Containing, Chemically Cross-Linkable, Thermoresponsive Macromers for Bone Tissue Engineering. Biomacromolecules, Article ASAP; DOI: 10.1021/bm500175e

Press release: Rice University; available at http://www.eurekalert.org/pub_releases/2...050714.php

Figure: A new hydrogel invented at Rice University turns from liquid to semisolid as it moves from room temperature to near body temperature in an experiment. The material inside the tube quickly turns white as it gellates. Chemical links in the gel take longer to form, but help it hold its size and shape as a scaffold for growing new tissue. Credit: Jeff Fitlow/Rice University

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Hydrogel scaffold for new bone growth degrades when no longer needed00