So, when I picked this module way back in the summer of 2022, I had no idea that I would become engrossed in a world of engineering. I took biochemistry due to my complete lack of ability in physics, particularly mechanics. However, I soon realised this module ‘Engineering Replacement Body Parts’ dove into far more than the simplistic ignorant view inferred from the course name.

With the main areas of teaching being STEM cells, Prosthesis, Bionics, TISSENG and Ethics and Law I realised I would be receiving an answer to a question I did not know I had.

‘How does the potential of stem cells, engineered tissues and implanted devices in medicine impact the medical field as well as law and ethics in our society?’.

As a Biochemist the area that captured my interest the most was Ethics and Law and the rules and regulations around experimentation. Especially with the current rules changing on gender reassignment surgery for children which has sparked a lot of controversy on whether children can provide consent.

Within my course we have only briefly touched on ethical precautions when conducting experiments, which seems surprising judging how much they govern scientific research. One study that was only touched upon in a Neuroscience seminar I attended was the enforcement of electric shock therapy in the 1960s by Dr. Lauretta Bender. This was a known treatment for psychiatric disorders however she inflicted more than 100 children to shock therapy with the youngest being three years old! Maybe it was because my younger brother had just turned three or the fact that I couldn’t believe that it was not just adults subjected to this treatment. I suddenly thought about a child’s right to autonomy and further what makes someone fit or unfit to give consent. 

It is easy to forget the significance of scientific regulations and ethical boards, as well as how some members of the scientific community only 50 years ago engaged in actions that would now be regarded as atrocities and unbelievable, as shows like Stranger Things and films like Suckerpunch almost trivialise and make medical scandals feel dystopian and alien to us.

The Government currently have legislation on getting informed consent for user research which is shown below directly from the government website:

If this had previously been in place many children would have been saved from the torment and emotional damage they ensued. There are three main views that can be taken when weighing up harm, benefit and autonomy. 

• Libertarian
• Paternalistic
• Utilitarian

All of them would agree that low-risk research where participants are fully informed is an allowable argument. However, both a utilitarian and paternalistic argument would suggest that low risk research where participants do not know they are taking risks is justifiable. This is something I particularly struggled to understand. 

Consent always seemed so black and white, simple yes and no, but when it comes to informed consent, how can a child be fully informed when they aren’t even fully formed?

A lecture by Dr. Alex Dickinson on prosthetic implants highlighted how patient satisfaction rates are a rationale for continued research into implants. I remember learning in Year 2 about how biofilms were one of the major difficulties faced when it came to implants and wanted to look more into what is being done to combat this.  

According to the National Joint Registry in 2013, 34% of knee and hip implants had to be replaced due to infection. Infections of implants result in the patient experiencing similar symptoms to before they had the implant, such as swelling in the area, pain and stiffness.  I can see how frustrating this is for the patients as it must feel like you have gone back to square one. Furthermore, replacing an implant is quite costly and takes up time that could have been used for new patients who require the implant in the first place, not to mention the invasiveness of the treatment.

How does the infection occur ?

In able to understand how treatments are manufactured, I needed to understand how the infection occur in the first place. From my own knowledge, I know that bacteria and other microorganisms enjoy smooth surfaces where they attached on to and  form biofilms. Here they form communities where they ‘live’ which has a constant and stable supply of nutrients to support their survival.

What I did not know is that there are two ways that this infection can occur on the implant. The first being during the surgical procedure – where the bacteria can come from the individuals flora or the operating environment. The second is the microorganisms can be carried by the blood and form a biofilm- this one occurs after the surgery has occurred. In both ways the biofilm maturation occurs over time and it takes some years before it becomes harmful.

By the time the infection is discovered the biofilm has developed so much it becomes difficult for the clinicians to identify what microorganisms that are included in this making it harder to treat them as it is time consuming and requires heavy reach.

What about antibiotics and our immune system ?

Well… multiple studies have shown that biofilms show hight antibiotic resistance due to their formation. When in the biofilm, the bacteria switches off certain genes which could be targeted by these antibiotic rendering them ineffective. Remarkably, one study showed that some bacteria in the biofilm were able express certain phenotypes which would result in the removal of the antibiotics! Due to the lack of blood supply within the implant the immune system is limited.

Current Treatments

So far the most common treatments is DAIR- debridement, antibiotics and implant retention. This procedure involves reopening the implant, washing it out with fluid, removing damage tissue followed by a course of antibiotics , which can vary in duration. The success rates of this treatment vary  due to the heterogeneity of the patients, length of infection and  type of infection. Typically study’s show that DAIR has a higher success rate with acute infection and when the infection has progressed there is an increased chance of the patients reinfection and them requiring are placement  implant. Although there are some success with this treatment , it is still invasive and costly and relies on early detection – which we have seen before is quite difficult.

Future Prospects

I decided to look into research about future therapies or ways to improve the DAIR. I learnt that in order for clinicians to improve the success of DAIR, they are looking into trying to detect the high levels of antibody within the patients so they could be able to intervene at an earlier point. But the invasiveness and time consuming aspects still remain

Antimicrobial peptides have been showing promising results in therapeutics. They already exist in our innate immune system. Their cationic charge allows them kill a range of different microorganisms but not attack the mammalian cells. In addition to this there are other antibiotics such as fluoroquinolones and rifampin penetrate biofilms. This type of treatment ideal but so far researchers have been unable to find a mechanisms for these in vivo.

So if the treatments are lacking, what can be done to prevent this from occurring in the first place? This is where I came across an fascinating paper about looking potential biomaterials which prevent biofilms from forming. The paper looking at what can be done to the biomaterials of the implants to  interfere with the biofilm formation. They conducted a lot of experiments on the metal roughness and tried coating different materials onto the implant. Most notably, the rougher the metal and coating the implants with ions made it harder for the biofilm to form. With this information I began to think that perhaps copper , an ion producing mental could be used to make the implants. Well after reading up on this making copper implants would be impractical but researchers are looking into coating the implants with copper – due to its antimicrobial properties

I was particularly interested in coating the implants with an acylase activity which is turn disrupts quorum -sensing. From studying my course quorum sensing is the way bacterial communicates with each other – so being able to stop that would be detrimental in winning the war against biofilms.

Concluding thoughts

Coming into this, I honestly thought that there was not much hope for resolving biofilm infection of implants. This is mainly because there is not really a reliable , non-invasive treatment for this. However in this case I believe the best way beat biofilm is prevention. The biomaterials look highly promising- although a lot of research has to be done to assure that it doesn’t affect human cells. this is definitely an area that I will keep up to date on as there could be huge developments soon.

A prosthetic hand acts as a substitute limb for those that may be missing one from birth or lost one later in life. There are several types of prosthetic hands, all functioning in their own way and prioritising different aspects for the user. Electrically-powered prosthetic hands offer a range of functions, however are costly. Alternatively, cosmetic prostheses are more affordable but do not provide active function. Because of this, many users ultimately settle with a prosthetic that does not perform to their expectations.

Recently, I watched a documentary that looked into resolving this issue. It showed Masahiro Yoshikawa, a professor from the Faculty of Robotics and Design at the Osaka Institute of Technology, focusing on creating highly functional protheses, while keeping costs low. This is an aspect of prosthetic research that I view as important, as it is essential that prosthetic users are not denied choice because of affordability. Prior to his research, a myoelectric prosthetic was the superior option. This consists of a prosthetic with sensors that detect electrical signals created by muscle movement from the residual limb, triggering a motor. The motor then converts the signal into finger movements, allowing the user to grasp objects. However, this technology is expensive and the prosthetic is heavy, which is not ideal for most individuals.

Offering a low-cost, lightweight, and highly functional prosthetic

Yoshikawa reviewed the manufacturing process for myoelectric prostheses, and figured out that one reason they are so expensive to make is due to the plaster moulds that have to be created prior to making the socket. He concluded that using a 3D printer to create the socket would eliminate the need to produce a mould beforehand, both decreasing manufacturing time and manufacturing cost.

Another improvement Yoshikawa set to develop was the issue of the myoelectric prosthetics malfunctioning after prolonged use. This was because, when users perspirate inside the device, it resulted in a short circuit between electrodes and disrupted the detection of the myoelectric signals. He proposed that, by measuring the height of the muscle as a change in distance, this signal instead could be used to generate motion. More specifically, through using a photoelectric sensor inside the socket, the muscle bulge created by movement of the residual limb will produce a change in distance from the sensor, detected via infrared rays, activating the motor. Consequently, with the sensor not directly resting on the skin and being surrounded by the urethane foam, the issue with perspiration is resolved alongside the benefit of the photoelectric sensor being significantly cheaper than the myoelectric one.

Since the filming of this documentary, this foundation has been used to create a three-fingered device and a five-fingered device, with realistic options available through the use of a silicone glove.

This video shows the three-fingered device in action.

Through researching this topic, it has enabled me to understand the components that need to be considered when developing new prostheses, along with providing equal options for everyone. By developing a lightweight, cost effective, highly functional prosthetic, this has opened up options for individuals who would have previously been limited to a purely cosmetic prosthetic. Hopefully, with the advancement of technology, like what Yoshikawa has demonstrated, a wider range of prosthetic options will be available which users can choose from dependent on their lifestyle.

Check out the link below for the documentary:

https://www3.nhk.or.jp/nhkworld/en/ondemand/video/2015286/

In the first lecture regarding the ethics and law of using humans in research, we discussed the case of Julius Hallervorden, a prestigious German physician and neuroscientist who operated during World War II. Hallervorden’s research sparked great debate, as he received up to 2000 brain samples from the Nazi euthanasia programme, where certain German physicians were authorised to select patients under the age of 18, “deemed incurably sick, after most critical medical examination”, and then administer to them a “mercy death” [1]. While he did not directly participate in the programme, using these materials Hallervorden published several articles during the post-war years furthering the understanding of multiple neurological disorders, even having a condition named after him and his colleague, Hugo Spatz, Hallervorden-Spatz disease.

Furthermore, Hallervorden denied any responsibility for the deaths of his subjects, stating “If you are going to kill all those people, at least take the brains out so that the material can be utilized”, as he continued, “I accepted the brains, of course. Where they came from and how they came to me was really none of my business”. Hearing Hallervorden’s opinion added to the controversy, trying distance himself from the atrocities, while others would argue he is complicit with the forced euthanasia.

After reading related articles and scouring YouTube, I discovered bioethicist Jürgen Peiffer, who reported multiple papers published by Hallervorden that likely used data collected from brain sections of “euthanasia” victims [2], also noting the terminology used, as he referred to patients brains as ‘material’, which Peiffer believed showed a lack of compassion. After Hallervorden’s death in 1965, the science community began to object his publishments, culminating in the renaming of Hallervorden-Spatz disease nearly 40 years later in 2003 [3].  

During the lecture, we discussed in small groups our own opinions on this case, which allowed me to reflect on all views regarding Hallervorden’s research. I realised just how controversial this topic was, as it showed the unanimously horrific practices of the Nazi party still influenced modern research.

My personal opinion

Coming from a scientific background, I can understand the desire for knowledge that drives researchers ambitions to discover the unknown. I believe this is a principle found in all individuals but is more prominently hard wired into scientists. That being said, I also believe that everybody, scientist or not, should have a moral compass strong enough to realise what is ethically and morally acceptable.

I do not believe Hallervorden was an evil individual, rather his ambitions and desires were filled without limit, which ultimately hindered his moral judgement. In other words, he realised he had an opportunity to conduct revolutionary medical research and took it without considering the ethical and moral implications of his work.

Whether or not we should use his research is an infinitely complex debate. On the one hand, the research has contributed to our understanding of complex disorders, potentially saving countless lives. Additionally, to not use the research would be a waste, a similar justification to Hallervorden’s. Contrastingly, I believe it is not acceptable to credit someone who was complicit with such atrocities, and to do so would be inconsiderate and insensitive to the patients families, as well as tarnishing the reputation of scientific research as a whole.

To conclude, I believe Hallervorden should be striped of his accolades and no longer be credited for his research, however, I think the research should be used as it could save lives and provides a foundation for more research in this area.

References

1. Proctor, R.N. and Proctor, R., 1988. Racial hygiene: Medicine under the Nazis. Harvard University Press. Available here.
2. Peiffer, J., 1999. Assessing neuropathological research carried out on victims of the ‘Euthanasia’ programme: With two lists of publications from Institutes in Berlin, Munich and Hamburg. Medizinhistorisches Journal, (H. 3/4), pp.339-355. Available here.
3. Hayflick, S.J., Westaway, S.K., Levinson, B., Zhou, B., Johnson, M.A., Ching, K.H. and Gitschier, J., 2003. Genetic, clinical, and radiographic delineation of Hallervorden–Spatz syndrome. New England Journal of Medicine, 348(1), pp.33-40. Available here.

From internal procedures like knee or hip joint replacements, to external ones like replacement limbs, prosthetics allow hundreds of thousands of people each year increased quality of life and mobility. As someone with a background in animal ecology, I became interested in how prosthetics for animals might be created; they have very different morphology and requirements to humans, with stronger forces being exerted on them, and the animal’s natural behaviour needs to be considered.

One example of prosthetics being used for non-human patients is, of course, Prof. Noel Fitzpatrick, who treats pets around the UK, for example Oscar, a cat who lost his hind limbs, and had them replaced with Intraosseous Transcutaneous Amputation Prosthetics (ITAP), where holes are drilled into the residual limb’s bone and the implants are then attached, allowing the skin to bond to the prosthetic, creating ‘pegs’ onto which the limb itself can then be attached following a recovery period. Similar methods for bone-anchored limb prosthetics are being considered for humans, though still in its early stages. Even a recent study performed on 16 cats and 4 pigs finds issues with infection at the stoma, and a high failure rate of integration. Regardless, it is true that prosthetic techniques being developed in the field of veterinary science can have implications for human medicine.

But what I was most interested in was wild animals, whose requirements would be a lot different to pets’. That’s how I ran into Winter, a bottlenose dolphin whose tail was lost in a crab trap in 2005. Over a year and a half later, with a lot of work from a dedicated team, a prosthetic tail was completed and fitted onto Winter. Unlike an arm or a leg, a tail can’t simply stay solid as the animal moves, but must move along with it, hold its position under water and under the force of a large animal using it to propel its movement, not cause further injuries to Winter, and, of course, perform its function as a tail. The resulting material created from this research, WintersGel, can now be used for human patients, especially athletes as it is softer and distributes weight more evenly than other liners, reducing pain and pressure exerted by the limb.

There are many other cases of prosthetics being used in wildlife, from an injured Bald Eagle with a prosthetic beak, to a young elephant with a prosthetic foot, to a 3D-printed leg for a Secretary Bird at a bird park who injured her leg, and, prevented from engaging in her natural behaviours, began engaging in behaviour associated with poor welfare. There has even been a tiger in east Germany who, experiencing pain from arthritis, had a hip replacement, although a more recent operation hasn’t been as successful, and the tiger who underwent it had complications. This, as well as other cases where operation may have had more negative than positive consequences for the animal, raise the importance of ethical considerations in wildlife prostheses. Are these operations always necessary? Do they increase the animal’s quality of life, or do they add unnecessary stress to an animal’s life who might not survive for very much longer, or who, unable to engage in their full behavioural repertoire, might exhibit stereotypies or other negative behaviours? With humans, we can operate on the basis that each of us should have autonomy over what happens to our own bodies, and that informed consent is crucial in these and other procedures, but who should get to decide when the patient can neither understand what is happening nor communicate their preferences on the matter?

From the lectures on tissue engineering, I found the idea of fixing the body with the same materials that make up the body really interesting, and how this can help with rejection which is faced by foreign materials in the body. This led me to look more into recent advances in tissue engineering, where I came across this news article about a new biomaterial with the potential for healing damaged heart tissue after a heart attack.

What is it?

A team at the University of California San Diego has developed a new hydrogel, which is a polymer chain complex that can hold a lot of water. The hydrogel contains extracellular matrix (ECM), from the myocardium, or heart muscles. The ECM has been decellularized to isolate the matrix, enzymatically digested, and fractionated. In the body, cells exist inside a matrix, which contains proteins and other molecules to give structure to tissues and aid in cell communication. The original hydrogel that was developed was too large to target leaky blood vessels. This issue was solved by centrifuging the gel in its liquid stage to remove larger particles.

How does it work?

The hydrogel is injected intravenously, taking advantage of the bloodstream to access hard to reach organs. After a heart attack, gaps form between the endothelial cells which line blood vessels. When the hydrogel reaches the damaged tissue, it binds to these cells, bridging these gaps and promoting new cell growth and repair, and also reducing inflammation. The gel takes roughly 3 days to degrade after administration.

In their initial clinical trial, the gel was directly injected into the heart muscle. This came with the disadvantage of having to wait at least a week after the heart attack, as injecting the damaged tissue by needle directly after is likely to do more harm than good. Intravenous injection can be done immediately. The hydrogel can then work together with other treatments such as angioplasty or a stent. In addition, the gel is more evenly distributed around the tissue rather than being concentrated around the site of injection.

The Next Steps

This new way of administering the gel has been successfully tested on rodents and pigs to treat damaged heart tissue. The research group are looking to get authorisation from the FDA to perform human trials, with plans to start in the next couple of years. They are also exploring the potential of the hydrogel to treat other inflammatory diseases such as traumatic brain injury and pulmonary arterial hypertension with preclinical trials on rodents.

In the UK there are around 100,000 hospital admissions every year for heart attacks- or one every five minutes. Over the past 50 years, there has been major advances in treatment and survival. In the 19080s roughly 25% of people having a heart attack would die, nowadays, if treated quickly, the chance of dying during a heart attack is 2-4%. In the future this number will hopefully reduce even more with advances in bioengineering.

References

British Heart Foundation, 2023. UK Factsheet. [Online]
[Accessed 9 March 2023].

Spang, M. T. et al., 2022. Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues. Nature Biomedical Engineering, 29 December, Volume 7, pp. 94-109.

Thomas, M., n.d. Focus on: Heart Attacks [Interview] n.d.

University of California – San Diego, 2023. Groundbreaking Biomaterial Heals Tissues From the Inside Out. [Online]
Available at: https://scitechdaily.com/groundbreaking-biomaterial-heals-tissues-from-the-inside-out/ [Accessed 8 March 2023].

Recently my family received the unfortunate news that my grandmother has been diagnosed with stage 1 Parkinson’s disease. This came as a shock to me and since then I have been trying to educate myself about this condition and figure out the best way to support her.

Parkinson’s disease (PD) is a progressive neurological disorder affecting more than 10 million people worldwide. This is caused by the degeneration of dopamine-producing cells in a region of the brain called the substantia nigra leading to a decrease in the dopamine neurotransmitter that is essential for controlling movement and coordination. This decrease in dopamine leads to motor symptoms including hand tremors, slow movement, limb rigidity, imbalance, and non-motor symptoms including cognitive impairment, mental health disorders, sleep disorders, and so on.

What causes this degenerative condition?…we don’t know!

The underlying mechanisms responsible for the deterioration of nerve cells associated with PD are not yet fully understood. Researchers believe a combination of genetic and environmental factors cause the dopamine-producing cells to die. Some of the factors that have been linked to PD include aging, exposure to certain toxins, head injuries, and genetic mutations (Parkin and PINK1 gene).

5 stages of Parkinson’s disease

PD can start with mild symptoms and go unnoticed, but as the condition worsens, symptoms become more obvious and can have a big impact on daily life.

Treatments, not cures: Living with Parkinson’s disease

• Medications: Drugs such as levodopa, dopamine agonists, MAO-B inhibitors, and COMT inhibitors can help manage the motor symptoms of PD.
• Physical therapy: Regular exercise can help improve motor function, muscle strength, increase flexibility, and reduce stiffness, which can be very important in the early stages of the disease.
• Deep brain stimulation: This procedure involves implanting a device called a neurostimulator which sends electrical impulses to specific parts of the brain to lessen the symptoms of PD.

My grandmother’s doctor has prescribed medication to help manage her symptoms and advised her to stay active in any way she can. Is this enough? PD usually develops in people over 60 but it can also occur in younger people, what about them? Is this the only solution?

Unsatisfied with this information, I continued researching until I came across a useful article that offered fresh new perspectives; Stem cells: Parkinson’s treatment breakthrough. Preclinical studies using mesenchymal stem cells have shown promising results for treating PD; aiming to reduce neuroinflammation, modulate the immune system to prevent disease progression, and repair or even replace, the damaged or lost, dopamine-producing cells in the brain. This could lead to significant improvements in motor symptoms like tremors, stiffness, rigidity, and difficulty with movement.

While more research is required to confirm the effectiveness of stem cell therapy on PD, this gives me hope for the future. Stem cells are so powerful, they can renew themselves indefinitely, and be manipulated in the lab to develop into specific cell types, possessing a tremendous potential to be used in therapies to treat a variety of diseases and conditions, why not PD be one of them?