After attending a lecture by Dr Dickinson and Professor Browne on prosthetic limbs, I found myself intrigued by the manufacturing process behind them. After doing some of my own research, I stumbled upon the recent revolution in 3D printing. In more developed countries such as the United Kingdom and the United States, prosthetics are readily accessible and are usually fitted around 2-6 months after surgery. However, this is far from the case in lower-income countries like Cambodia. It is estimated around 100 million people worldwide require a prosthetic limb; 80 percent of whom do not even have access to this resource. Recent advances in 3D printing technology have made it much easier to construct prosthetic limbs, making it quicker and more affordable as well as being far more tailored to the individual.

A photo showing a donated prosthetic from Guillermo Martínez to a Kenyan child, synthesised from 3D printing

The benefits of 3D printing

There are several benefits to using 3D printing technology for prosthetic limbs, including:

1. Customisability: Traditional prosthetics can be difficult and time-consuming to customise, often requiring manual adjustments and moulds. With 3D printing, prosthetic limbs can be designed and printed based on precise measurements of the amputee’s residual limb, resulting in a better fit and greater comfort.
2. Affordability: Traditional prosthetic limbs can be expensive, with some models costing tens of thousands of dollars. 3D printing technology offers a more affordable alternative, making prosthetics accessible to a wider range of people.
3. Rapid production: Traditional prosthetics can take several weeks or even months to produce. With 3D printing, prosthetic limbs can be designed and printed in a matter of hours or days, allowing for faster delivery to those in need.
4. Reduced waste: Traditional prosthetic limbs often require a significant amount of material waste, as moulds must be created and adjusted multiple times. 3D printing eliminates the need for moulds and produces little to no waste, making it a far more environmentally-friendly option.
5. Innovation: 3D printing technology is constantly evolving, with new materials and designs being developed all the time. This means that prosthetic limbs can continue to improve and become more functional over time, offering even greater benefits to amputees.

Overall, the capability of 3D printing to produce highly tailored prosthetic limbs is one of its main benefits. Contrary to conventional manufacturing methods that call for moulds and human adjustments, 3D printing enables swift and simple production of accurate dimensions and customised designs. As a result, amputees can get prosthetic limbs that match their unique requirements and preferences, enhancing their quality of life entirely.

The drawbacks

While 3D printing technology has many benefits for the production of prosthetic limbs, there are also some potential drawbacks or challenges to consider:

1. Limited strength and durability: Some 3D printed materials may not be as strong or durable as traditional materials used in prosthetic limbs, which could result in a shorter lifespan or increased risk of breakage.
2. Quality control: There is currently limited regulation and oversight of 3D printed prosthetic limbs, which could result in lower quality or safety standards compared to traditional prosthetics.
3. Limited accessibility: While 3D printing technology has the potential to make prosthetic limbs more affordable and accessible, there are still limitations to its widespread availability, particularly in lower-income or developing regions.
4. Limited design options: While 3D printing technology allows for greater customisability, there may be limitations in terms of available designs or features compared to traditional prosthetic limbs.
5. Training requirements: As 3D printing technology is still relatively new, there may be a lack of specialised training or expertise in the field of 3D printed prosthetic limbs, which could result in lower quality or inconsistent results.

It is important to consider that many of these challenges are currently being addressed by researchers and developers working in the field of 3D printed prosthetic limbs. As the technology continues to improve, it is likely that many of these issues will be resolved over time.

After attending lectures on stem cells and tissue engineering, I found myself to be very intrigued by chimeras and the diversity capabilities of specific cells. Specifically, the possibility that we could potentially grow human organs in another species, with the intention of organ donation, was something that seemed so unbelievable to me. This provoked me to research further into how close to achieving this we may be, as there is also bound to be ethical issues surrounding this worth discussion. Currently, the NHS weekly statistics reports that 6963 people are currently waiting for organ transplants in the UK. The NHS also reports that 30 in 100 patients experience organ rejection following the implementation of a donated organ. Therefore, I believe it to be an important issue worth researching to find more solutions for.

What research is currently being done?

Investigation of this subject lead me to find the research done by Dr. Pablo Ross who has used his extensive veterinary experience, combined with his in-depth knowledge of stem cells to conduct experiments on creating a human-pig chimera. So far, the research and its limited funding, has lead as far as creating chimeras which contain approximately every 1 in 100,000 cells of the pigs being human because pigs and humans are such distant relatives. With this being the extent of current research, it is fair to say we are not yet at a point where human-pig chimeras are able to provide functional help in the medical world. The end goal is that one day we may grow an organ that is fully human or at least made up of enough human cells that it may overcome the prevalent issue of organ rejection.

How ethical is it?

The immediate issue that should be addressed is that testing on animals can not always be seen as entirely ethical as they cannot provide their own informed consent for such procedures and research to take place. It is because of this that humans must make the decision to evaluate if the potential harm to the animals outweighs the benefits of the research or not. The benefits of this line of research, if successful, could potentially lead to a huge reduction in organ rejection, as well as a largely reduced waiting time for all those suffering with organ failure. However, the concept of breeding animals for the purpose of organ donation to humans, which is potentially a very invasive procedure, raises many ethical concerns. My thoughts are that if the research is to be done at all, it may be, in some sense, more fair to use animals who are already being bred with the purpose of being used for their meat as then more of the animal can be used, instead of disregarded.

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.

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?