Mechanically Conditioned Tissues Offer Hope for Better Healing

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Stephanie Bryant shows her team's patent-pending bioreactor used for mechanically conditioning tissues.
Stephanie Bryant shows her team's patent-pending bioreactor used for mechanically conditioning tissues.

Anyone who has ever experienced a broken bone, torn muscle, or inflamed tendon can testify to the importance of exercise in proper healing.

From a science and engineering standpoint, however, there is much that isn't known about the physiological process known as "mechanotransduction."

"I'm really intrigued by how cells sense and respond to mechanical loading," says Assistant Professor Stephanie Bryant, who specializes in biomaterials and tissue engineering.

"There's so much we don't know about the physiology—for example, why cartilage degenerates when joints aren't used."

Bryant is focusing her attention in the laboratory on the engineering of cartilage, tendon, and bone, all of which sense and respond to mechanical forces. She and her students are designing synthetic biomaterials called hydrogels, which act as scaffolds to support and promote healing while compression and tensile forces necessary to the growth of tissue cells are applied. The hydrogels, created through a process called photopolymerization, contain living cells that when given the right cue direct natural tissue growth.

Using a patent-pending, high throughput bioreactor that her team designed and built in the chemical and biological engineering department, the researchers can mimic the effects of walking, running, and even various cycles of rest and exercise like those in everyday life.

Bryant's group also submitted a patent on a newly engineered biomaterial scaffold that has been shown successful in retaining the new matrix that tissue cells are producing while undergoing mechanical forces. These forces typically initiate the flow of fluid, which can flush some of the newly synthesized tissue away.

The next step is to optimize the mechanical stimulation provided in the bioreactor with the newly engineered scaffold, and thereby set the stage for the growth of mechanically robust cartilage tissue, Bryant says.

The National Institutes of Health and the National Science Foundation (through its CAREER Award program) have been funding the research. This year, the university and state of Colorado also provided a $200,000 grant to develop the mechanically engineered tissue for craniofacial reconstruction. The funding came through the Bioscience Discovery and Evaluation Grant Program, which is aimed at filling the funding gap that exists between universities and the private sector, and thereby accelerating the commercialization of promising inventions.

Four students graduated with PhDs from Bryant's group last year, while six more doctoral students continue working on related projects.

Other areas of research in Bryant's lab include developing methods that will keep implanted hydrogels from being "walled off" by the physiological environment of the body. In laboratory tests, the researchers have shown that the human body produces the same foreign-body reaction to the hydrogel as it would to the implantation of a pacemaker or other non-biological implant.

"There's an early inflammatory response, followed by a walling off, or encapsulation, of the foreign substance," Bryant says. "This has been looked at in the medical field, but we're looking at it with regard to tissue engineering, where we are not getting good integration of the biomaterial with the surrounding native tissue."

Certain proteins are being tested to inhibit localized inflammation, allowing for better integration and healing, she says.

Bryant earned her PhD in chemical engineering at CU-Boulder in 2002, working with Distinguished Professor Kristi Anseth, who is one of the leaders of CU's biotechnology initiative. Bryant then spent two and a half years as a postdoc at the University of Washington before joining the CU faculty, where she is now the Patten Assistant Professor of Chemical and Biological Engineering at CU-Boulder as well as an assistant professor of craniofacial biology at the Anschutz Medical Campus.

Bryant was named CU-Boulder's New Inventor of the Year in 2007, and she is excitedly anticipating her department's move into state-of-the-art facilities at the Jennie Smoly Caruthers Biotechnology Building in 2012. The new building is currently under construction on Boulder's East Campus.

"What's most exciting (about the move to the new building) is the integration of people from the Colorado Initiative in Molecular Biotechnology, the biochemistry division, and chemical and biological engineering," Bryant says. "If my students have more interactions with people from these other fields, then who knows where our research program will be in another five years? There are lots of different avenues we could go."

CU-Boulder's new PhD program in interdisciplinary quantitative biology will help to facilitate a truly interdisciplinary environment. The program will offer course work outside of traditional academic boundaries; students can earn a certificate in interdisciplinary quantitative biology plus a PhD in any of eight different fields of science, mathematics, engineering, and technology.

Read more about CU's new biotechnology building.

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