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KRISTI S. ANSETH, THE FIRST ENGINEER TO BECOME AN HHMI INVESTIGATOR, HAS INVENTED NEW CLASSES OF HYDROGELS—SYNTHETIC BIOINSPIRED MICROENVIRONMENTS THAT SUPPORT AND INTERACT WITH LIVING CELLS. WORKING WITH CLINICIANS, CHEMISTS, AND BIOLOGISTS, THE UNIVERSITY OF COLORADO AT BOULDER RESEARCHER AND HER COLLEAGUES ARE DEVELOPING A FORM OF TISSUE ENGINEERING TO COAX THE BODY TO HEAL ITSELF.
Imagine that a soldier could quickly regrow the bones of his shattered leg, that a skier could donate a bit of her own cartilage to rebuild the protective cushion in her damaged knee, or that an implant of tailor-made brain cells could cure the shaking of Parkinson's disease.
That is the promise of tissue engineering, a field often called regeneration medicine. Clinicians, engineers, biologists, chemists, and materials scientists are joining forces to marshal the body's developmental and repair mechanisms to heal wounds, rebuild damaged tissues, and replace essential cells.
In my laboratory, our challenge is to design customized biomimetic gels, also called hydrogels, that imitate some aspects of the extracellular matrix—the natural three-dimensional microenvironment that encourages cell growth during development and wound healing and during normal tissue homeostasis. These artificial matrices already are being tested as structural supports for cell-built treatments such as joint repair. The next generation of gels will support cells' metabolic functions, such as insulin regulation for diabetes, and encourage cell-to-cell connections, as with neurons in the brain.
A second challenge is to learn the biomimetic cues that cells require to perform a desired repair. We may discover that our task is less to control natural processes than to trigger the right conditions so that the cells themselves can take on the job of building and organizing tissue.
A treatment now in clinical trials to repair the cartilage worn away from a skier's painfully damaged knee offers a simple example of the way a biomimetic gel works. Injected into the space within the joint, the hydrogel—which combines water with large macromolecules—is activated by beams of light to form a molecular mesh. This mesh forms a firm but flexible scaffold, rather like organized Jell-O, built in the presence of the patient's own cartilage-forming cells, which secrete tissue components that decorate the lattices of macromolecules like vines on a trellis. Stimulated by cues from the three-dimensional scaffolding, the cartilage-built structure gains strength and the artificial scaffolding begins to dissolve. Meanwhile, the skier exercises her knee, and mechanical forces refine the shape. Instead of a titanium joint replacement, she has regrown a natural cushion of her own cartilage to support her knee.
Photo: John Johnston
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