Consider going to a surgeon to have a diseased or injured organ removed for a fully functional, lab-grown material. This is science fiction and not reality as researchers today struggle to process cells into the complex 3D configurations that our bodies can master on their own.
There are two main barriers to accessing laboratory-grown organs and bones. The first is to use a biologically compatible 3D scaffold in which cells can grow. The second is to decorate that scaffolding with biochemical messages in the right arrangement to stimulate the formation of the organ or tissue you want.
In a major step toward realizing this hope, researchers at the University of Washington have developed a mechanism to modify naturally occurring biological polymers with protein-based biochemical messages that influence of cell behavior. Their approach, published the week of Jan. 18 in Proceedings of the National Academy of Sciences, uses near-infrared laser to bring chemical compliance of protein messages to scaffolds made from bio-polymers. such as collagen, a binding substance found throughout our bodies.
Mammalian cells responded as expected to the protein signals held inside the 3D scaffold, according to lead author Cole DeForest, UW’s associate professor of chemical and bioengineering. The proteins on these biological scaffolds stimulated changes in message pathways within the cells that affect cell growth, signaling and other behaviors.
These methods could form the basis for biologically based scaffolds that may one day make laboratory action figs, said DeForest, who is also an associate member with the UW Institute of Molecular Engineering and Sciences and UW Institute for Stem Cell and Regenerative Medicine. .
“This approach gives us the opportunities we have been waiting for to better control cell activity and violence in naturally occurring biomaterials – not just in a three- lateral but also over time, “DeForest said.” In addition, it makes use of highly precise photochemistries that can be controlled in 4D while preserving protein function and bioactivity to strange. “
DeForest’s colleagues on this project are lead author Ivan Batalov, a former UW postdoctoral researcher in chemical and bioengineering, and co-author Kelly Stevens, UW’s assistant professor in bio- laboratory engineering and medicine and pathology.
Their approach is the first for the field, controlling the spatial control of cell activity within naturally occurring biological materials as opposed to those derived from synthetically. . Several research groups, including DeForest’s, have developed light-based methods to modify synthetic scaffolds with protein markers. But natural biological polymers can be a more attractive scaffold for tissue engineering because they have biochemical properties in which cells are responsible for structure, communication and other purposes.
“Natural biomaterial like collagen tends to have many of the same signaling properties as those found in native print,” DeForest said. “In many cases, these types of substances keep cells ‘happier’ by giving them symptoms similar to the ones they would encounter in the body.”
They worked with two types of biological polymers: collagen and fibrin, proteins involved in bleeding. They each gathered in water-filled scaffolds called hydrogels.
The signals the team added to the hydrogels are proteins, one of the key messages for cells. Proteins come in many forms, all with their own unique chemical properties. As a result, the researchers designed their system to use a universal mechanism to bind proteins to hydrogel – the link between two chemical groups, alkoxyamine and aldehyde. Before accumulating hydrogel, they stained the collagen or fibrin precursors with alkoxyamine groups, all of which were physically blocked by a “cage” to prevent the alkoxyamines from reacting prematurely. The cage can be removed by ultraviolet light or by near-infrared laser.
Using methods previously developed in the DeForest laboratory, the researchers also added aldehyde groups to one of the proteins they wanted to bind to the hydrogels. They then combined the aldehyde-carrying proteins with the alkoxyamine-coated hydrogels, and used a short stroke of light to remove the cage covering the alkoxyamine. The exposed alkoxyamine readily reacts with the aldehyde group on the proteins, binding them inside the hydrogel. The team used masks with cut-out patterns, as well as changes to laser scan geometry, to create complex patterns of protein arrangements in the hydrogel – including the old UW logo, Seattle’s Space Needle, a monster and a 3D shape. the human heart.
The bound proteins were fully functional, delivering the signals the cells needed. Rat liver cells – when loaded onto collagen filters with a protein called EGF, which stimulates cell growth – showed signs of DNA reproduction and cell division. In a separate experiment, the researchers decorated fibrin hydrogel with a protein pattern called Delta-1, which activates a specific pathway in cells called Notch. When they introduced human bone cancer cells into the hydrogel, cells in the regions with the Delta-1 pattern activated Notch signals, while cells in areas without Delta-1 did not.
These experiments with several biological scaffolds and protein markers show that their approach could work for almost any type of protein signaling and biomaterial system, DeForest said.
“Now we can begin to create hydrogel scaffolds with many different signals, using our understanding of cell signals in response to specific protein compounds to alter critical biological function in time and space,” he said. .
With more complex signals loaded on filters, scientists could then try to control gas differentiation, a key step in turning science fiction into science fiction.
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The research was funded by the National Science Foundation, the National Institutes of Health and Gree Buildings.
For more information, contact DeForest at [email protected].
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