3d printed novel biomaterial mimics properties of living tissue
Imagine if surgeons could transplant healthy neurons into patients living with neurodegenerative diseases or brain and spinal cord injuries. And imagine if they could "grow" these neurons in the laboratory from a patient's own cells using a synthetic, highly bioactive material that is suitable for 3D printing.
By discovering a new printable biomaterial that can mimic properties of brain tissue, Northwestern Engineering researchers are now closer to developing a platform capable of treating these conditions using regenerative medicine.
A key ingredient to the discovery is the ability to control the self-assembly processes of molecules within the material, enabling the researchers to modify the structure and functions of the systems from the nanoscale to the scale of visible features. The laboratory of Samuel I. Stupp published a 2018 paper in the journal Science which showed that materials can be designed with highly dynamic molecules programmed to migrate over long distances and self-organize to form larger, "superstructure" bundles of nanofibers.
Now, a research group led by Stupp has demonstrated
that these superstructures can enhance neuron growth, an important finding that
could have implications for cell transplantation strategies for
neurodegenerative diseases such as Parkinson's and Alzheimer's disease, as well
as spinal cord injury.
"This is the first example where we've been
able to take the phenomenon of molecular reshuffling we reported in 2018 and
harness it for an application in regenerative medicine," said
Stupp, the lead author on the study and the director of Northwestern's
Simpson Querrey Institute. "We can also use constructs of the new
biomaterial to help discover therapies and understand pathologies."
Walking molecules and 3D printing- A new step towards innovation:
The new material is created by mixing two liquids that quickly
become rigid as a result of interactions known in chemistry as host-guest
complexes that mimic key-lock interactions among proteins, and also as the
result of the concentration of these interactions in micron-scale regions
through a long-scale migration of "walking molecules". The agile molecules cover a distance of 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 ropelike bundles.
"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 with Alexandra
Edelbrock, a former graduate student in the group. "This phenomenon is unique to the systems we have developed here."
Furthermore, 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.
Interestingly, 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 types of neural cells in order to study their interactions.
Signaling neuronal growth
The superstructure and bioactive properties of the material could have vast implications for tissue regeneration. 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.
One of the molecules in the new material integrates
a mimic of this protein that activates its receptor known as Trkb, and 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
the environment in which neurons differentiated from patient-derived stem cells
mature before transplantation.
Now that the team has applied a proof
of concept to neurons, Stupp believes he could now break into other areas of
regenerative medicine by applying different chemical sequences to the material.
Simple chemical changes in the biomaterials would allow them to provide signals
for a wide range of issues.
"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. Beyond these interventions, the materials could be used to build organoids to discover therapies or even directly implanted into tissues for regeneration since they are biodegradable."
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