To bring relief to this and other problems, University of Waterloo researchers have created a new type of wound dressing material using advanced polymers. This new dressing could enhance the healing process for burn patients and have potential applications for drug delivery in cancer treatment as well as in the cosmetic industry.

“To treat burn victims, we can customize the shape using a 3D printer, secondly, the material has fine-tuned surface adhesion, which is a key feature,” said Dr. Boxin Zhao, a professor in Waterloo’s Department of Chemical Engineering, whose team has made significant strides in developing intelligent hydrogel materials for use as a reusable wound dressing. “The material can easily adhere to the skin and be taken off. It’s a very delicate balance within the material to make the adhesion work.”

In developing the dressing, the researchers conducted a 3D scan of the patient’s face and body parts to customize it to an individual’s needs. This enables the dressing to make good contact with surfaces like noses and fingers, making it ideal for creating personalized wound dressings for burn patients.

The material also has applications for cancer treatment. In traditional chemotherapy treatment, a patient may need to be in a clinic for hours, which can be tiring and uncomfortable. This dressing can provide a constant drug release outside the clinic setting, alleviating some of the challenges associated with traditional methods.

The material used to create these smart dressings includes a biopolymer derived from seaweed, a thermally responsive polymer, and cellulose nanocrystals. The dressing’s thermal responsiveness allows it to warm on the skin and gently lower to room temperature. Additionally, when chilled in the fridge, the dressing expands but shrinks to a smaller size at body temperature, making it easier and less painful to remove. Also, the dressing is designed to provide time-release medication, allowing for longer-lasting pain relief.

“We also envision applications in the beauty and cosmetic industry,” said Zhao, Waterloo’s Endowed Chair in Nanotechnology. “Cosmetologists can utilize 3D scanning technology to analyze their clients’ facial features and customize hydrogel masks infused with specific facial and skin regimen products. Additionally, this innovative approach can benefit plastic surgeons.”

This research is proof of concept for Zhao’s Surface Science and Bio- nanomaterials Laboratory Group. The next step for Zhao’s research group is to continue improving the material’s properties to make it healthier and commercially viable.

A study highlighting the team’s progress was recently published in the Journal of Colloids and Interface Science.

It is well-known that the dopamine system is implicated in signaling reward-related information as well as in actions that generate rewarding outcomes. This can be investigated using either Pavlovian and operant conditioning experiments. Pavlovian conditioning describes how your brain makes an association between two situations or stimuli that previously seemed unrelated. A famous example is Pavlov’s experiment, where a dog heard a sound before receiving food. After several such pairings of the sound with food delivery, the sound alone began to cause the dog to salivate. Operant conditioning, or instrumental learning, differs from this in that the behavior of an individual is important to earn a food reward. Meaning that the individual after hearing a sound, has to perform a so-called operant action to receive the reward. In animal experiments, such a operant response is often the pressing of a lever.

Dopamine measurements in nucleus accumbens

In the final PhD paper of Jessica Goedhoop in collaboration with Tara Arbab and Ingo Willuhn from the Netherlands Institute for Neuroscience, they take a closer look at the role of dopamine signaling in learning and motivation. The team directly compared the two conditioning paradigms: male rats underwent either Pavlovian or operant conditioning while dopamine release was measured in the nucleus accumbens, a brain region central for processing this information. During the experiments a cue light was illuminated for a duration of 5 seconds. For the Pavlovian group, a food pellet was delivered into the reward magazine directly after the cue light turned off. For the operant conditioning group, turning off the cue light was followed by extension of the lever below the cue light into the operant box. The lever was retracted after one lever press, which immediately resulted in the delivery of one food pellet reward into the food magazine. If there was no lever press within 5 seconds after lever extension, the lever was retracted and no reward was delivered.

Sustained dopamine release in operant conditioning

Rats in both groups released the same quantity of dopamine at the onset of the reward-predictive cue. However, only the operant-conditioning group showed a subsequent, sustained plateau in dopamine concentration throughout the entire 5-second cue presentation (throughout cue presentation and before lever press). This dopamine sustainment was observed reliably and consistently throughout systematic manipulation of experimental parameters and behavioral training. Therefore, the researchers believe that sustained dopamine levels may be an intermediate between learning and action, conceptually related to the motivation to generate a reward-achieving action.

Ingo Willuhn: ‘There have been a lot of studies on dopamine. We have a decent idea of when dopamine is released in the brain, but there is still lots of discussion on what the precise variables are that determine such dopamine signaling. Essentially discussion on what dopamine “means.” To investigate this, scientists usually perform either Pavlovian or operant conditioning experiments. But they test slightly different things. Both have to do with learning an association between a neutral stimulus and a reward. But operant conditioning requires the motivation to perform an action in addition to that (to earn the reward). Therefore, we compared the two types of conditioning in the same experiment.’

Adding a piece to the puzzle

‘Our results bring together the two camps of scientists that often battle with each other: one says that dopamine is a so-called reward-prediction error signal, meaning that dopamine is released when something better than expected happens, and is suppressed when something worse than expected happens. It is a learning (or teaching) signal. The other camp says that this is not true. They say that dopamine has something to do with motivation. Increased dopamine release will invigorate the subjects and they work harder to get the reward. There have been a few attempts in the past to bring these two camps together, but there is still need for more knowledge on the subject.’

‘What we saw in our study is that only in the operant-learning task dopamine levels stayed high. It seems that the motivation is encoded in this plateau. Reward prediction is the initial dopamine peak, but how much the signal stays up, reflects motivation. Thus, our paper suggests that there is a possibility that dopamine is involved in both, learning and motivation. The next steps will be to get more details out of this. We need to replicate the experiments and make them more sophisticated. The more sophisticated you make it, the more precise our predictions have to be. We are going to build on it and see whether it still holds up.’

Implications

‘Dopamine is not only involved in everyday life but also in disorders such as addiction, Parkinson’s disease, and schizophrenia. Because of the two camps existing, there is disagreement about what happens exactly. For example, some researchers say that when addicts take drugs dopamine release increases and as a consequence all the environmental cues become more meaningful. Addicts learn that these cues are associated with the drug and they take more and more drug, because they are constantly reminded of the drug everywhere. In this view, addiction is misguided learning. Other researchers would say that motivation to take the drug intensifies with more frequent drug intake, because the drug elevates dopamine release. This study indicates that it may be both. Depending on the precise timing, both systems could be the driver, and both could be involved.’

‘This is also relevant for the clinic. Prescribed drugs can influence both learning and motivation systems at the same time: and then it can get messy. If you give schizophrenic patients classic antipsychotic medication, they become slow and cannot act much because their motivation system is down. Parkinson’s patients take pro-dopamine drugs essentially because they lost their dopamine, but some patients start to gamble because their dopamine system is on overdrive suddenly. We cannot influence learning and motivation components separately. As soon as you give a drug it is going to hit all of it, so it is good to keep that in mind.’

What happens in a pigeon’s brain during sleep?

The question of whether similar processes also take place in birds has remained unresolved until now. “The last common evolutionary ancestor of birds and mammals dates back about 315 million years, to the early days of land vertebrates,” says Professor Onur Güntürkün, head of the Biopsychology Department at Ruhr University Bochum. “Yet the sleep patterns in birds are remarkably similar to those in mammals, including both REM and non-REM phases.”

To find out what exactly happens when birds sleep, the researchers used infrared video cameras and functional magnetic resonance imaging (fMRI) to observe and record the sleeping and wakeful states of 15 pigeons specially trained to sleep under these experimental conditions.

The video recordings shed light on the sleep phases in the birds. “We were able to observe whether one or both eyes were open or closed, and to track eye movements and changes in pupil size through the pigeons’ transparent eyelids during sleep,” explains Mehdi Behroozi from the Bochum team. Simultaneously, the fMRI recordings provided information about brain activation and the flow of cerebral spinal fluid in the ventricles.

Dreams of flying

“During REM sleep, we observed strong activity in brain regions responsible for visual processing, including in those areas that analyze the movement of a pigeon’s surroundings during flight,” says Mehdi Behroozi. The team also noticed activity in the areas that process signals from the body, especially from the wings. “Based on these observations, we think that birds, just like humans, dream during REM sleep, and might be experiencing flight in their dreams,” adds Mehdi Behroozi.

Additionally, the scientists noticed activation of a particular brain area known as the amygdala during these phases. “This suggests that if birds experience something similar to our human dreams, pigeons’ dreams might include emotions as well,” says Gianina Ungurean from the Avian Sleep Group at the Max Planck Institute for Biological Intelligence. This hypothesis is supported by the fact that the birds’ pupils contract rapidly during REM sleep, like they do during courtship or aggressive behaviors while awake, as recently demonstrated by Gianina Ungurean and colleagues.

Washing out the day’s dust

Like in humans, the flow of cerebral spinal fluid through ventricles increases during non-REM sleep in pigeons. However, the team discovered for the first time, in any animal, that the flow diminished dramatically during REM sleep. “We think that the increased flood of blood into the brain during REM sleep, which supports the elevated brain activity, might block the cerebral spinal fluid from moving from the ventricles into the brain,” explains Niels Rattenborg, head of the Avian Sleep Group. “This suggests that REM sleep and its functions might come at the expense of waste removal from the brain.”

However, the scientists are also entertaining the possibility that REM sleep contributes to waste removal in unexpected ways. “At the onset of REM sleep, the influx of blood increases vessel diameter. This might force cerebral spinal fluid that entered the space during non-REM sleep to flow into the brain tissue, and enhance the outflow of fluids carrying waste products,” says Gianina Ungurean.

The researchers speculate that the process of cleaning the brain during sleep may be especially crucial for birds. Since their brains have a higher density of neurons in comparison to mammals, the removal of waste products may require more efficient — or more frequent — flushing cycles. As birds experience more and shorter REM phases during sleep than mammals, the associated frequent surge of blood might help to keep their densely packed brains free of harmful waste products.

Tell us about your dreams!

In the future, the team plans to explore REM sleep’s potential role in waste removal. In addition, they are thinking about ways to learn about the content of a pigeon’s dream. “We hope to train birds to report if and what they just saw upon awakened from REM sleep. That would be an essential step towards establishing whether they dream,” explains Gianina Ungurean. But even without a detailed dream analysis, the new findings already help us to better understand the role of sleep, in birds as well as in humans. They highlight the importance of sleep in maintaining a healthy brain and preventing cognitive decline — and they also imply that dreaming has a very long history.

The study was conducted by the Bochum Biopsychology team as well as researchers from the Max Planck Institute for Biological Intelligence, the Max Planck Institute for Neurobiology of Behaviour, the Neurophysiology Department at Ruhr University Bochum and the Université Claude Bernard Lyon.