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A universal solution for regenerative medicine

Northwestern Medicine News Mar 13, 2017

In the Northwestern’s Louis A. Simpson and Kimberly K. Querrey Institute for BioNanotechnology (SQI) Stupp’s laboratory had engineered molecules able to self–assemble into nanofibers thousands of times thinner than a human hair that can mimic cell structures and biological signaling. The technology can be used to regenerate tissues and organs spanning from bone and cartilage to muscle and brain tissues. Hsu hoped it could rebuild bone in spine therapy. Wellington Hsu, MD, and and his wife Erin Hsu, PhD, research assistant professor of Orthopaedic Surgery – both resident faculty in the SQI – sought to apply Stupp’s novel nanofibers to spinal fusion animal models.

Working together, the Stupp–Hsu team developed a new version of the nanofiber material that they believe will be a better bone graft substitute. Made from collagen and self–assembling nanofibers, their “nanoslurry” is a malleable paste that binds to the native growth factors in a patient’s own body, enhancing natural healing ability.

In challenging healing environments, this “slurry” can also deliver BMP–2, a growth factor protein critical in the regeneration of bone. The BMP–2 protein is then released over time to induce bone growth, so lower amounts of the protein are required for successful fusion, which could minimize side effects. In either iteration, this paste will allow surgeons to adapt the material to fill any size bone defect.

“We have these synthetic nanogels that we know can promote bone formation, but to work in the operating room, they have to be readily accessible and implant easily,” Erin Hsu says. “This slurry will allow the nanofiber gels to be used in a more universal fashion.”

Stupp’s research is based on supramolecular chemistry, which explores how molecules interact with each other and how they self–assemble and function. The underlying science behind the field was recognized in 1987 when Donald J. Cram, Jean–Marie Lehn and Charles J. Pedersen received the Nobel Prize in Chemistry.

Stupp spearheaded the study of “supramolecular biomaterials,” self–assembling materials that can be designed to interact specifically with cells. “What makes this field exciting is getting to use cutting–edge science – it’s new for everybody – and having an impact on lifespan and quality of life for people,” says Stupp, who is also a professor at Feinberg, the Weinberg College of Arts and Sciences, and the McCormick School of Engineering.

Stupp’s work focuses on developing materials that mimic the nanoscale architecture of extracellular matrices surrounding mammalian cells. These materials have the ability to display biological signals that can interact with receptors and cause cells to migrate, proliferate or differentiate.

The nanofibers that Stupp has engineered resemble collagen or fibronectin fibers, both structures of the extracellular matrix. They can be built from a combination of amino acids, nucleic acids, lipids and sugars, which allows them to degrade into nutrients for cells. The scientists believe they can incorporate any biological signal in these nanofibers to achieve a specific regenerative medicine target.

In work published in the journal Nature Materials, his lab showed how the length of nanofibers is critical to the survival and proliferation of mammalian cells.

Furthermore, in a paper published in the journal Science, Stupp’s lab developed a new type of nanofiber that combines two kinds of polymers, those formed with covalent bonds and others formed with non–covalent bonds. The strongly bonded covalent polymer acts as a skeleton for structure and the weakly bonded non–covalent polymer forms a compartment that is soft like a gel. This soft component can be altered, removed, or regenerated by adding small molecules, allowing the hybrid polymer to have different features.
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