What if we could transplant healthy neurons into patients with neurodegenerative diseases or brain and spinal cord injuries? And what’s more interesting is what if we can grow these neurons in the laboratory using a patient’s own cells with the help of a synthetic, highly bioactive material suitable for 3D printing.
New research from Northwestern University is close to its discovery of a new printable biomaterial that can mimic the properties of brain tissue.
One important thing to the discovery is the ability to control the self-assembly processes of molecules within the material. This has helped them to change the structure and functions of the systems from the nanoscale to the scale of visible features.
The research showed that materials can be designed with highly dynamic molecules programmed to migrate over long distances and self-organize to form larger, “superstructured” bundles of nanofibers.
The team led by Samuel I. Stupp has shown that these superstructures help in improving neuron growth and can play an important role that could have implications for cell transplantation strategies for neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, and spinal cord injury.
Stupp added that this was the first example where they have been able to take the phenomenon of molecular reshuffling which they reported in 2018 and use it for an application in regenerative medicine. We can use these constructs of the new biomaterial to help discover therapies and understand pathologies.
Walking molecules and 3D printing
The new material, created by mixing two liquids which quickly become rigid because of chemical interactions. These interactions, also known as host-guest complexes are also similar to the key-lock interactions among proteins.
The agile molecules cover a distance thousands of times larger than themselves in order to band together into large superstructures. At the microscopic scale, this migration causes a transformation in structure from what looks like an uncooked chunk of ramen noodles into rope-like bundles.
Tristan Clemons, a research associate in the Stupp lab and co-first author of the paper with Alexandra Edelbrock, a former graduate student in the group explained that the 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 which is what makes this phenomenon unique to other systems developed here.
We see that as the dynamic molecules move to form superstructures, large pores open that allow cells to penetrate and interact with bioactive signals that can be integrated into the biomaterials.
The mechanical forces of 3D printing disrupt the host-guest interactions in the superstructures and cause the material to flow, but it can rapidly solidify into any macroscopic shape because the interactions are restored spontaneously by self-assembly.
This also enables the 3D printing of structures with distinct layers that harbor different neural cells in order to study their interactions.
Signaling neuronal growth
Neurons are stimulated by a protein in the central nervous system known as brain-derived neurotrophic factor (BDNF), which helps neurons survive by promoting synaptic connections and allowing neurons to be more plastic. BDNF could be a valuable therapy for patients with neurodegenerative diseases and injuries in the spinal cord, but these proteins degrade quickly in the body and are expensive to produce.
A molecule in the new materials integrates a mimic of this protein which activates its receptor known as Trkb. The team found that neurons actively penetrate the large pores and populate the new biomaterial when the mimetic signal is present. This could also create an environment in which neurons differentiated from patient-derived stem cells mature before transplantation.
The team believes they could break into other areas of regenerative medicine by applying different chemical sequences to the material with their idea. Simple chemical changes in the biomaterials would allow them to provide signals for a wide range of tissues.
“Cartilage and heart tissue are very difficult to regenerate after injury or heart attacks, and the platform could prepare these tissues in vitro from patient-derived cells,” Stupp said. “They could then transplant these tissues to help restore lost functions. Beyond these interventions, the materials could build organoids to discover therapies or even directly implanted into tissues for regeneration since they are biodegradable.”
Alexandra N. Edelbrock, Tristan D. Clemons, Stacey M. Chin, Joshua J. W. Roan, Eric P. Bruckner, Zaida Álvarez, Jack F. Edelbrock, Kristen S. Wek, Samuel I. Stupp. Superstructured Biomaterials Formed by Exchange Dynamics and Host–Guest Interactions in Supramolecular Polymers. Advanced Science, 2021; 2004042 DOI: 10.1002/advs.202004042