In a proof-of-concept experiment, researchers have developed a material that can be designed to strongly encourage neurone growth.
Researchers at Northwestern University have recently come a step closer to developing a regenerative treatment for neurodegenerative conditions. This comes in the form of a new biomaterial, capable of enhancing and encouraging the growth of neurones, ready to be transplanted into humans. The research could help lay the groundwork to create new therapies to aid treatment of life-altering conditions like Parkinson’s or Alzheimer’s.
The Stupp laboratory, where this research took place, has done previous research that focused on understanding the reversible self-assembly of molecules found in the body. These hierarchical structures are used by living things to grow biological structures and regulate certain cellular processes. However, recreation of these structures in synthetic environments has proven difficult.
In a paper published in 2018, the Stupp laboratory designed molecules that could migrate over a long distance and self-assemble to form larger, so-called “superstructures.” Now, they have built on this work to create bioactive superstructures – ones which have biological effects on cells.
The biomaterial is formed by mixing two chemicals – in what is known as a host-guest interaction – whose structures slot together like a lock and key. The team here utilised a well-studied host-guest interaction between two specific molecular groups, ß-cyclodextrin and adamantane.
This interaction had been used previously to create drug-release systems and biosensors.
The biomaterial self-assembles on its own. “Typical biomaterials used in medicine like polymer hydrogels don’t have the capabilities to allow molecules to self-assemble and move around within these assemblies,” said Tristan Clemons, a research associate in the Stupp lab and co-first author of the paper. “This phenomenon is unique to the systems we have developed here,” he added.
The superstructure formed is also highly porous – a favourable property to allow penetration from outside cells. This allows bioactive signals to be integrated into the material.
To demonstrate bioactivity, the team used a mimic of a protein found in the body known as brain-derived neurotrophic factor (BDNF). BDNF essentially sustains neurones in the body by promoting synaptic connections.
By integrating the mimic into the biostructure and studying its effect in the presence of neurones the team saw that neurones actively grew into the biostructure to penetrate and populate it. Observations at how the neurones grew into the structure led the team to propose that the porous nature of the superstructure enhances neurone growth.
The mechanical properties of the structure also allow for 3D printing. Due to its self-assembling nature, even if the host-guest interaction is disrupted and the layers shear off, the structure reconstitutes itself. This means the structure can be 3D printed without major disruption to the shape or functionality.
The researchers propose that this may also allow neurones to be printed into spatially defined scaffolds to simulate the complexity of neural tissue for study – something that is seen as an important goal in this field.
Stupp believes that regenerating neurones is just the beginning and hopes to utilise this concept in other areas of regenerative medicine.
“Cartilage and heart tissue are very difficult to regenerate after injury or heart attacks, and the platform could be used to prepare these tissues in vitro from patient-derived cells,” Stupp said. “These tissues could then be transplanted to help restore lost functions,” he added.