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New platform helps treat neurodegenerative diseases through regenerative medicine

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Imagine if a surgeon could transplant healthy neurons into a patient with a neurodegenerative disease or brain or spinal cord injury. And imagine if these neurons could be “grown” in the laboratory from the patient’s own cells using synthetic, highly bioactive materials suitable for 3D printing.

Researchers at Northwestern University are approaching the development of a platform that can treat these conditions using regenerative medicine by discovering new printable biomaterials that can mimic the properties of brain tissue.

A key element of the discovery is the ability to control the self-assembling process of molecules within the material, allowing researchers to change the structure and function of the system from the nanoscale to the scale of visible features.

Samuel I. Stupp’s lab published a 2018 paper in the journal Science This has shown that the material can be designed with highly dynamic molecules programmed to travel long distances and self-assemble to form larger bundles of “superstructured” nanofibers.

Currently, a research group led by Stupp has shown that these superstructures can promote neuronal growth. This is an important finding that can affect cell transplant strategies for neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease and spinal cord injury.

This is the first example that can be applied to regenerative medicine by utilizing the phenomenon of molecular modification reported in 2018. New biomaterial structures can also be used to help discover treatments and understand medical conditions.“”

Samuel I. Stupp, Principal Writer and Director, Simpson Kelly Institute, Northwestern University

A pioneer in supramolecular self-organization, Stupp is also a professor of the Board of Trustees in Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering and has been appointed by the Weinberg University of Arts and Sciences, McCormick Engineering and Feinberg School of Medicine. I am. medicine.

The paper was published in the journal today (February 22nd) Advanced science..

Walking molecule and 3D printing

The new material quickly becomes stiff as a result of interactions known in chemistry as host-guest complexes that mimic key-lock interactions between proteins, and as a result of micron-scale concentration of these interactions. Created by mixing two liquids, a region due to the large-scale movement of “walking molecules”.

Agile molecules cover thousands of times their own distance to bind to large superstructures. On a microscopic scale, this movement transforms what looks like an uncooked chunk of ramen into a rope-like bundle.

“Typical biomaterials used in medicine, such as polymer hydrogels, do not have the ability for molecules to self-assemble and move around in these aggregates,” said a researcher at Stupp Labs in this paper. Co-lead author Tristan Clemons said. Alexandra Edelbrock, a former graduate student of the group. “This phenomenon is unique to the system we have developed here.”

In addition, the migration of dynamic molecules to form superstructures opens large pores that allow cells to penetrate and interact with bioactive signals that can integrate into biomaterials.

Interestingly, the mechanical forces of 3D printing interfere with the host-guest interaction in the superstructure and cause the material to flow, but the interaction is macroscopic because it recovers naturally through self-organization. It can solidify rapidly into shape. This also allows 3D printing of structures with separate layers containing different types of nerve cells to study interactions.

Signaling neuronal growth

The superstructure and bioactive properties of the material can have a significant impact on tissue regeneration. Neurons are stimulated by a protein in the central nervous system known as brain-derived neurotrophic factor (BDNF). It helps neurons survive by promoting synaptic connections and increasing neuronal plasticity. BDNF has the potential to be a valuable treatment for patients with neurodegenerative diseases and injuries of the spinal cord, but these proteins are rapidly degraded in the body and are expensive to manufacture.

One of the molecules of the new material integrates a mimic of this protein that activates a receptor known as Trkb, and the team actively penetrates large pores in the presence of mimic signals. And discovered to bury new biomaterials. It can also create an environment in which neurons differentiated from patient-derived stem cells mature before transplantation.

As the team applied the proof of concept to neurons, Stupp believes that by applying different chemical sequences to the material, it can penetrate other areas of regenerative medicine. Simple chemical changes in biomaterials allow them to signal a wide range of tissues.

“Cartilage and heart tissue are very difficult to regenerate after injury or heart attack, and the platform can be used to prepare these tissues in vitro from patient-derived cells,” Stupp said. Says. “These tissues can be transplanted to help restore lost function. Beyond these interventions, the material builds organoids to discover cures or is biodegradable. It can even be transplanted directly into the tissue for regeneration. “

This work was supported by the Center for Regenerative Nanomedicine at Northwestern University’s Simpson Kelly Institute, the Graduate Research Fellowship through the National Science Foundation, and the American Australian Association Fellowship.

The title of this paper is “Supramolecular biomaterials formed by exchange dynamics and host-guest interactions in supramolecular polymers”.

Source:

Journal reference:

Edelbrock, AN, et al.. (2021) A suprastructured biomaterial formed by exchange dynamics and host-guest interactions in supramolecular polymers. Advanced science.. doi.org/10.1002/advs.202004042..

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