In a major step toward transforming this hope into reality, researchers at the University of Washington have developed a technique to modify naturally occurring biological polymers with protein-based biochemical messages that affect cell behavior. Their approach, published the week of Jan. 18 in the Proceedings of the National Academy of Sciences, uses a near-infrared laser to trigger chemical adhesion of protein messages to a scaffold made from biological polymers such as collagen, a connective tissue found throughout our bodies.
These methods could form the basis of biologically based scaffolds that might one day make functional laboratory-grown tissues a reality, said DeForest, who is also a faculty member with the UW Molecular Engineering and Sciences Institute and the UW Institute for Stem Cell and Regenerative Medicine.
"This approach provides us with the opportunities we've been waiting for to exert greater control over cell function and fate in naturally derived biomaterials dimensional space but also over time," said DeForest. "Moreover, it makes use of exceptionally precise photochemistries that can be controlled in 4D while uniquely preserving protein function and bioactivity."
DeForest's colleagues on this project are lead author Ivan Batalov, a former UW postdoctoral researcher in chemical engineering and bioengineering, and co-author Kelly Stevens, a UW assistant professor of bioengineering and of laboratory medicine and pathology.
Their method is a first for the field, spatially controlling cell function inside naturally occurring biological materials as opposed to those that are synthetically derived. Several research groups, including DeForest's, have developed light-based methods to modify synthetic scaffolds with protein signals. But natural biological polymers can be a more attractive scaffold for tissue engineering because they innately possess biochemical characteristics that cells rely on for structure, communication and other purposes.
They worked with two types of biological polymers: collagen and fibrin, a protein involved in blood clotting. They assembled each into fluid-filled scaffolds known as hydrogels.
The signals that the team added to the hydrogels are proteins, one of the main messengers for cells. Proteins come in many forms, all with their own unique chemical properties. As a result, the researchers designed their system to employ a universal mechanism to attach proteins to a hydrogel - the binding between two chemical groups, an alkoxyamine and an aldehyde. Prior to hydrogel assembly, they decorated the collagen or fibrin precursors with alkoxyamine groups, all physically blocked with a "cage" to prevent the alkoxyamines from reacting prematurely. The cage can be removed with ultraviolet light or a near-infrared laser. The tethered proteins were fully functional, delivering desired signals to cells.
"Now we can start to create hydrogel scaffolds with many different signals, utilizing our understanding of cell signaling in response to specific protein combinations to modulate critical biological function in time and space," he added.
With more-complex signals loaded on to hydrogels, scientists could then try to control stem cell differentiation, a key step in turning science fiction into science fact.
MEDICA-tradefair.com; Source: University of Washington
