Bioengineers have created an intricate 3D polymer tissue scaffold that is capable of supporting delicate neurons by using a laser etching process.
It is hoped that small fragments of these ‘loaded’ polymers could eventually be transplanted into patients with conditions such as Alzheimer’s and Parkinson’s disease, as well as potentially for spinal injuries and stroke.
Early clinical trials in primates and humans have shown that injecting a solution of neural cells directly into the brain shows some benefit for degenerative conditions. However, the approach simply relies on neurons fortuitously finding their correct position and then integrating.
‘By injecting them you put a lot of stresses on them, so a lot of them die,’ project lead Dr Frederik Claeyssens of Sheffield University told The Engineer. Many of those that survive don’t actually stay at the injury site, added Claeyssens.
Tissue scaffolds are one potential solution and have become increasingly commonplace in regenerative medicine for things such as bone, cartilage and skin. However, neural tissue presents an altogether greater challenge for researchers.
‘They [neurons] have a whole architecture of support cells surrounding them in a precise geometrical alignment, which is difficult to replicate,’ said project collaborator Maria Farsari of the Foundation for Research and Technology (Hellas) in Greece.
While advanced manufacturing techniques such as 3D printing have shown promise for some tissue scaffolds, they are simply not accurate enough for neurons.
The research group therefore began experimenting with photopolymers, which can be fabricated using laser pulses.
The team start with a low molecular weight pre-polymer, based on liquid polylactide resin, then render it photocurable by attaching methacrylate groups to the hydroxyl end groups.
A beam of an ultrafast infrared laser is tightly focused into the photosensitive material, initiating a polymerisation process that creates the required internal structures. These structures are limited only by the potential of the laser and the researchers have demonstrated the technique by etching microscale sea-shell patterns.
In addition, even smaller holes and struts can be fabricated to facilitate the efficient delivery of nutrients to the neurons.
Crucially, the material degrades in the human body to form lactic acid, a naturally occurring chemical that can easily be removed, leaving the regenerated neural network behind in the required size, shape and structure.
The team has showed that the scaffold can support neurons for an unprecedented six days, but the aim is to be able to support a whole network for much longer since neurons take far longer to fully mature than other cells types.
‘Ideally you want a timescale in the order of months so you can really tune the degradation rate to match the physical properties of properties of the cells,’ Claeyssens said. ‘It’s the start of something that I hope becomes a much bigger project … to really build up a new part of the brain after, for example, ischemic stroke.’