The concept of 3D printing in general is fascinating to me, especially the idea that designs, both creative or functional, can be produced from computer modelling. I have experience with using such printers (both before and during university), and was intrigued when I found out through the lectures that they can be used in combination with stem cells; other examples of its medical applications are producing custom-tailored prosthetics and printing of tissues. As someone who has only printed using plastics, this topic appealed to me.

What is Bioprinting?

Bioprinting is a process very similar to typical 3D printing using plastic or metal, albeit replacing such materials with desired cell types mixed into a gel (e.g. gelatine) to create what is known as bioink. The mixture is then printed layer-by-layer until the desired structure has been produced. There are three main strategies for bioprinting:

• Inkjet – heat or ultrasound is used to produce pressure to force material from the extruder
• Microextrusion – mechanical means of releasing material
• Laser-assisted – releases cells via the pressure generated by a laser on an absorbing layer

Bioprinting has promise in its applications for printing tissues and organs, such as ears for those suffering from microtia, through printing their cells into a replacement ear. This reduces the need for patients to undergo more invasive surgery.

Other Applications of 3D Printing

Another way in which 3D printing can benefit patients is through indirect means; through creating accurately scaled replicas of organs undergoing surgery, such as hearts, surgeons can plan the surgery ahead of operating. The video below documents how Lucas Ciulean, a child born with an uncommon heart abnormality, was able to recover after surgery in which a replica 3D printed version of his heart was studied ahead of time. When I first watched it, I found it thought-provoking that the technology I had been using for years was capable of providing such valuable insights to patients with atypical conditions. I also believe this video raised an important point regarding minors undergoing surgery; by allowing parents to visualise the surgery planned for their child, these replicas can provide the parents with some comfort and reassurance. In my opinion, this is of the utmost importance since patients, or patients’ guardians, should feel informed and comfortable about any planned procedures.

Another interesting application of 3D printing has been displayed by MIT engineers, in which a prosthetic heart has been produced from soft plastic. The process started similar to the previous example, by taking scans of the patient’s heart and reproducing a 3D model from them; however, it deviates from the prior example since the model is then printed in a softer, flexible plastic. By fitting sleeves around the heart replica, it can mimic the rhythmic pumping of an actual heart through a pneumatic system. This is an interesting contrast to the idea of bioprinting a heart, although I have concerns regarding its viability due to the need for attachment to a pumping mechanism which may impact the patient’s comfort.

My Final Thoughts

The technique of 3D printing has been an interest of mine for years, and expanding this knowledge to the applications discussed above has been a rewarding journey. The current research state of bioprinters is really impressive and by building on the current knowledge, this technology will hopefully become more widely available to aid patients in need. I think that research should continue to innovate in both classical plastic printing, as well as in bioprinting to provide patients with more choices, and a greater level of reassurance and control that the option chosen is best for them.

I recently read a novel by Norman Doidge called ‘The Brain That Changes Itself’, and a chapter that caught my attention was on phantom limb pain. After reading this chapter, I realised that people who have lost limbs have to endure more problems than just adjusting to life without a hand or leg. They also must deal with excruciating pain that, to us as outsiders, does not exist. Many of us do not have this problem. However, many people in this world do. There are around 500 million amputees who have sadly lost a leg or arm due to disease, war, or accident. I believe the use of prosthetics and their advancement can help alleviate the pain.

The phantom pain phenomena

People who have this problem sometimes experience something known as phantom limb pain. This is when an amputee perceives pain in a limb that is no longer there. One of the main theories that draws my attention is the Central Theory: the brain tries to recreate a memory of the lost limb but fails because it does not receive feedback. I find this to be such an interesting phenomenon because, currently, there’s no guaranteed way to treat it; around 60-80% of amputees experience phantom limb pain. I then began wondering if there are any ways that people have managed to help others with this problem, and interestingly, I found this fascinating article about a man who helps people with mirrors.

How prosthetics can help.

After reading this, I began to wonder if prosthetics can help with this problem. Rather than using mirrors, the integration of a prosthetic with peripheral feedback may reduce the pain.

Many kinds of prosthetics exist, from a toe to an entire leg. Scientists are trying to improve prosthetics every day with new innovations. These new innovations can help people who have missing limbs live a higher quality of life.

A paper published in 2018 found that leg amputees using an electrocutaneous feedback prosthetic were able to alleviate phantom limb pain. Furthermore, another paper discussed a biological interface developed by the University of Michigan. They developed a new approach which involves a small graft of muscle tissue surgically attached to the end of a severed nerve in an amputee’s arm. This is known as the Regenerative Peripheral Nerve Interface(RPNI). The researchers managed to demonstrate that RNPIs attached to the peripheral nerves will contract when the person thinks about contracting. This links back to the Central theory as the brain receives the feedback it looks for.

 I find this incredible because we can ‘trick’ the brain into believing that the limb is still there.

How far can they go?

From what I have been reading, I can extrapolate that the true potential of prosthetics lies in the full integration of the brain and machine.

However, this raises concerns for me as there are ethical issues. For example, when they become advanced enough, people may opt to remove their limbs willingly to have an advanced body part. Where do you draw the line on this? Is mutilation of one’s own body acceptable if it’s consensual?

These are all questions that really must be considered when the time comes, and I personally believe that physical enhancement should not be allowed without reason.

Films like the Six Million Dollar Man (1973) and Robocop (1987) explore the possibility of replacing body parts. Now, nearly 50 years on, are we any closer to turning fiction into reality?

Travelling to the hospital for my first anatomy session was truly eye opening and brought back memories of watching Robocop in school. Examining cadavers, joint replacements, and implants with the smell of formaldehyde lingering in the air was something I didn’t think I would experience. As I saw what progress was being made towards what these films predicted, I left wondering how did we get here and what’s next?

Current advancements:

Following a lecture on sensing technology, I began to appreciate the next step in this evolution and reflected on what this means for people with disabilities, prosthetics, and even paralysed individuals. This technology is present in Elon Musk’s Neuralink implant, which uses sensors to create a brain-computer interface to restore movement and eyesight. It works by sensing signals in the brain, interpreting the users intentions and sending this information to a receivers to have its effect. Pairing this sensing technology with prosthetics will prove to be vital in making artificial body replacements functional and more lifelike. However, due to a lack of testing, there is still alot unknown about the long term effects.

But, what’s the catch?

While these advancements may improve one’s quality of life, there is the potential to create social inequality, therefore ensuring fair distribution and affordability is important. Further, the long term impacts of new technologies like Neuralink implants must be investigated due to concerns regarding nonmaleficence, autonomy and consent. Individuals must be made aware of the treatments and possible long term impacts before making decisions. As we advance, we must consider the effects of these body replacements and what it means to be human? To me, expressing ourselves through our emotions and interactions with the people around us is key. Loosing limbs and the ability to do certain things affects this, so if someone needs a prosthetic, joint replacement, implant, or another type of body replacement in order to feel like themselves, then I think they should have that opportunity. Equally, it is important question, how far is too far? Are there certain limits we shouldn’t exceed and are there any exceptions?

Final thoughts:

This is a complex topic, and we are limited in what we can achieve but advancements are continuously being made. There is a lot to consider regarding ethics, and each situation is different, but we must balance innovation with what is right. It is important to note that this is an interdisciplinary effort, with the need for engineers, lawyers and scientists and this is something I am interested in getting involved in. We have come a long way, but we still have some way to go before we see our own Robocop.

An Organ Crisis

As someone passionate about donating my organs when I die (since what better use is there for the loss of my life than to preserve the life of another), I was shocked to learn that despite 4025 organ transplants being carried out in the UK in 2016-17, 457 patients died on the transplant waiting list due to the shortage of transplantable organs, and that BAME patients are less likely to find a suitable donor than white patients. Increasing the supply of organs is imperative to saving lives.

Where Else Can We Source Organs From?

Initially, researchers looked into xenotransplantation, the transplant of animal organs into humans, and these procedures have had some limited success. Researching xenotransplantation introduced me to a new potential source of organs driven by advancements in stem cell technology: researchers are attempting to grow human replacement organs in animal ‘carriers’ by creating chimeras. The ability of early animal embryos to grow specific organs is genetically removed, and stem cells from the patient are inserted into the embryo in an effort to induce the stem cells to grow into these organs. In one experiment, some pig embryos successfully grew early kidneys with majority human cells. By using induced pluripotent stem cells, adult stem cells from the patient which have been ‘reprogrammed’ to revert to a pluripotent state, the risk of rejection and ethical implications associated with organ donation and stem cell use are avoided.

Ethical Concerns: Animal and Human Welfare

Not all ethical concerns are avoided. As a vegetarian who cares deeply about animal wellbeing, I am concerned about the welfare of the animals producing these organs. While I believe it is ethically correct to choose a person’s life over an animal’s life (it brings about the most ‘good’, as philosopher Jeremy Bentham would argue), millions of animals die yearly for the progression of medicine. Thousands more would do so for the growth of organs.

Some are worried about the potential of the stem cells forming sex cells, potentially resulting in chimera producing offspring with human genes, or brain cells giving the chimera a human ‘consciousness’, thus blurring the line between ‘human’ and ‘animal’. If a pig with human brain cells is produced, do we consider them human enough to be required ethically to do the most ‘good’ for them? Or are they still animal enough to be sacrificed for human health? These issues are summarised in this video by AJ+:

Another concern I have is disease transmission between the animal donor and human recipient: zoonosis. Although this is much less of a concern with this procedure than with xenotransplantation, individuals receiving these transplants will be significantly immunocompromised and, thus, more vulnerable to potential zoonoses from the transplanted tissue if the disease crosses the species barrier within the carrier animal so must be considered. I think we need to contemplate the mental well-being of the patient—the fear of disease compounded with the fear of rejection and stress of recovery may drive patients away from accepting animal-derived organs, as well as religious reasons if they are of a faith which prohibits the consumption of specific or all animals. I would struggle to make this decision due to my beliefs.

Due to the various ethical issues involved in organ growth in chimeras, I think many approaches should be considered for increasing the supply of replacement organs, emphasising a balance of animal welfare, ethics, and patient preferences. This is a good case study; what is the balance of ethics and progress that we consider acceptable?

I have had an interest in stem cells since beginning my degree. Following a lecture on stem cells I attended, I found myself more curious about their applications and how they are attained. I was told umbilical cords are a good source of embryonic stem cells which are pluripotent (the most useful!) and my mum in fact told me she left my umbilical cord and placenta with the nurses to be used to harvest stem cells for those who need it. These cells are typically used in cancer, immune deficiency and genetic disease treatments. I found this super fascinating and I was proud that I, somewhat, contributed to that.

Stem Cells in Therapies

Stem cells used in disease treatment are already naturally lineage restricted, such as the transplantation of haematopoietic stem cells for blood cancers as discussed in our lecture. At the same time, some therapies may benefit from more undifferentiated stem cells, like human embryonic stem cells (hESCs) or potentially more ethically attained induced pluripotent stem cells (iPSCs). The limitations of using these pluripotent cells is that they result in the creation of a heterogeneous mixture including undesired cells, which as discussed in an article I saw, are difficult to expand and maintain in vitro, making in vivo applications more difficult. Further advantages and disadvantages of these cells are shown in the following image:

Scientists have weighed up these pros and cons and are now creating a different kind of stem cell that is much more specific for those cells that don’t have endogenous multipotent stem cells already.

Parkinson’s and Stem Cells

To investigate this further, I looked specifically at the use of lineage restricted stem cells in the treatment of Parkinson’s Disease (PD) which I have a personal interest in. For context, PD is a neurodegenerative disease characterised by progressively worse tremors and slow movements. It is unclear its direct cause, but stem cells are a trending mode of treatment. Scientists use pluripotent stem cells and treat them to become dopamine-producing neurones. Following legal guidelines from the Human Fertilisation and Embryology Act 1990, researchers have used embryonic cells from IVF programmes before 14 days of embryonic age. They also used iPSC since their discovery. But, these do not cure Parkinson’s. So what can be done to try to cure this disease?

An article I saw on researching this issue discusses their success with the use of lineage-restricted undifferentiated stem cells, from pluripotent cells. They found that 69% of these cells differentiated into the desired cell type (dopamine releasing neurones), a significant number compared to only 25% of hESC. This is a great result! They have kickstarted the research into lineage-restricted stem cells for PD (and I’m sure it has inspired people to try the method for other diseases )and emphasises how stem cell engineering is becoming a vital tool and could lead to potential cures for various diseases. I learnt there is more to stem cells than just pluripotency and they are more intricate than I had thought.

My final thoughts

I believe stem cell engineering and the potential around the creation of the ‘ideal stem cell’ is something that more people need to be educated on. There are still unresolved ethical questions but only through more education and understanding will we find the best ways to manage all expectations. It is exciting to think about the future applications of stem cells, what discoveries will be made and the overall benefits to all from this work.

45 years ago, Louise Brown shocked the world as the first ‘test-tube baby’. Whilst in vitro fertilisation (IVF) was initially met with a knee-jerk revulsion, Louise’s birth has since been a turning point in the treatment of infertility. Could a child developed from artificial gametes undergo this same path?

As an aspiring clinical embryologist, I champion assisted reproductive technologies (ART) such as IVF. However, when I came across the idea of assisted reproduction using artificial gametes, termed ‘in vitro gametogenesis (IVG)’, my reaction was immediately apprehensive.

In the same manner as how IVF practice was initially received as scientists ‘playing god’, my thoughts concerned whether IVG fits into the natural order. Although artificial gametes produce artificial embryos, would full prenatal development of these cells lead to artificial life? This question brought my mind to Kazuo Ishiguro’s science fiction novel ‘Never Let Me Go’ which delves into the meaning of humanity through the lens of human cloning as a means of organ donation. Despite their unconventional origins of conception and development, I was moved to read the injustices imposed on the clones who processed our same fully human thoughts and feelings. Whilst I don’t find the novel’s cloning institutions morally or ethically appropriate, this warmed me to IVG technology and the belief that children potentially born from artificial gametes would still hold valuable and meaningful lives.

What IVG could have to offer

The more I researched the applications of IVG within the broader context of society, the more my support for this putative technology grew.

IVG obtains gametes via reprogramming somatic cells into pluripotent stem cells. Therefore, it offers infertile couples, and even same-sex couples, the ability to generate viable gametes and have genetically related offspring.

If made readily accessible, IVG may offer an alternative to the standard hormonal stimulation for egg retrieval, alleviating women from the physical and emotional demands of the procedure.

Due to DNA-damaging chemotherapy and radiation treatment, IVG would be especially useful amongst cancer patients who may not have the time to conduct cryopreservation at the risk of delaying urgent anti-cancer treatment.

IVG would also provide an unlimited production of embryos, opening more avenues for developmental research.

Ethical considerations

While IVG has demonstrated success in mice, significant research and resolution of ethical and legislative challenges are required before its applications become a clinical reality for humans.

The prospect of generating embryos from any somatic cell raises concerns regarding unauthorised gamete creation. For instance, it may enable celebrity DNA theft. Although legislation could mandate cell samples to only be obtained in clinical settings with formal consent, the system could be easily exploited.

Theoretically, ‘uni-babies’ may be possible, where a set of gametes are reprogrammed from a single individual.

It brings to question the impacts on adoption.

Combined with gene-editing tools like CRISPR, the unlimited supply of IVG embryos could potentiate embryo farming and accelerate the concept of ‘designer babies’.

With UK legislation ruling a 14-day cut-off for human embryonic research, it may be questioned whether this period should be extended for artificial embryos. However, particularly if IVG is used as ART, artificial embryos should be applied under the same legislation as natural ones.

A biotech startup, Conception, claims they are ‘quite close to being able to have proof-of-concept human eggs’ derived from blood cells. Although the successful application of IVG in humans is years away, I think it would be a revolutionary technology that positively eliminates reproductive barriers for future generations.

The concept for my summative blog emerged during my dissertation lab project, where I used HepG2 cells to assess the hepatoprotective impacts of chlorogenic acid against paracetamol induced liver toxicity. During this process I became familiar with cell culture, treating and assaying them most days, but when I came to seed the cells myself and prepare new culture medium, my attention was brought to foetal bovine serum. When researching the topic I found interest in the ethical debate surrounding the production of foetal bovine serum and the demand for alternatives.

Foetal bovine serum (FBS) is a key component of cell culture medium and is used extensively for research applications. It contains essential hormones and growth factors providing a rich culture system; supporting the widest range of cell types, including cell lines and primary cells.

Although figure 1 provides a thorough overview of the FBS production process, it fails to describe the actual harvest, the point of most concern. FBS is typically obtained by the cardiac puncture of cow foetuses sourced from cows found to be pregnant after slaughter. This is carried out once the foetuses are declared deceased and without the administration of anaesthesia.

An article from 2002 covers the proposed reasons behind the ethical concerns surrounding FBS production and the potential for foetuses to experience pain during the process. One of the primary ethical concerns regarding the harvesting procedure involves the resistance of mammal foetuses to anoxia; the complete loss of oxygen supply to the body or brain. Mammals possess protective mechanisms allowing maintained brain function even after oxygen deprivation. These mechanisms include the ability to meet energy requirements via anaerobic respiration, the prioritisation of blood flow to critical organs such as the brain, and a reduced oxygen demand in the foetal brain, compared to adults. It is expected that the bovine foetuses have normal brain function at time of cardiac puncture, allowing us to assume that they are aware of the procedure and experience pain as a result. The paper then goes on to explore the timeline by which the cow foetus develops nociception and the ability to experience pain.

Since this paper is now over 20 years old I looked for more recent advancements. This led me to an article addressing the animal welfare ethics concerning FBS production and how the industry has altered it’s practises to avoid such concerns.

To summarise, the article discusses the debates regarding foetal sentience and consciousness, raising concerns about potential suffering during the procedure and proposes steps to minimise harm. They specifically make reference to the European Food Standards Agency (EFSA) recommendation to immediately open the uterus, stun and kill the foetus upon detecting pregnancy in a slaughtered cow. This ensures the foetus is unconscious and therefore doesn’t experience pain during the blood extraction. They suggest increased monitoring within the serum industry to ensure compliance with ethical standards and that by implementing such measures, the industry can demonstrate its commitment to ethical practise. Like the 2002 paper, they also conclude that it is time for researchers to adopt more modern approaches to human cell culture-based research and to move away from the use of FBS.

To conclude, at present time the production of FBS is deemed to be up to ethical standards providing individual producers follow legislation and guidelines provided. It’s clear that to fully address the concerns around animal welfare, alternatives to FBS are required. By adopting such alternatives, we can achieve greater scientific accuracy whilst demonstrating stronger ethical consideration.

References:

Jochems, C.E.A., van der Valk, J.B.F., Stafleu, F.R. and Baumans, V. (2002). The use of fetal bovine serum: ethical or scientific problem? Alternatives to laboratory animals : ATLA, [online] 30(2), pp.219–27. doi:https://doi.org/10.1177/026119290203000208.

McCann, T.J. and Treasure, C. (2022b). Addressing Animal Welfare Issues in Fetal Blood Collection for Fetal Bovine Serum Production. Alternatives to Laboratory Animals, 50(5), pp.365–368. doi:https://doi.org/10.1177/02611929221117992.

I came across a TedTalk titled ‘The artificial muscles that will power robots of the future’, which made me think – robots don’t look human at all, is there really a way to do that? An artificial muscle which is cheap, easily constructed and versatile? It cannot be?!

Many advances to improve the look of robots are already ‘in motion’. The invention of the Squidbot in 2020, was made to mimicked the swimming of a squid. The Pneumatic Artificial Muscle (PAM) was designed to aid the rehabilitation of patients diagnosed with polio. However, the HASEL actuator stood out to me, due to its versatility with its use, and the potential it has for improving both quality of life and broadening professional career paths for athletes. The concept of the HASEL (Hydraulic Amplified Self-healing ELectrostatic actuators) provides an unseen side of robotics, making the newly advancing AI robots look last season!

Their first prototype, Peano-HASEL actuator, was designed to contract linearly after electrical stimulation. The dynamic properties mimic those of an anatomical muscle. The elastomeric shell makes it easily recoverable from any force, comparative to the quick relaxation of the human muscles. The voltage applied to either end causes the liquid to migrate, producing a ‘contraction’. I believe soft robotics will go a long way for creating future real-life animatronics, which could even have the potential to function better as a result.

It doesn’t stop there! The Planar HASEL actuator was made to lift heavy objects. Electrical charge is applied to the insulating liquid, causing stretching of the polymer and horizontal shrinking, making it move vertically. The future for this specific design is bright; It could completely replace upper arm prosthetics for everyday use! It can even collect enough force to throw a ball in the air, supporting my opinion: the benefits of this development will be transitional through generations!

The Quad Donut HASEL prototype can run on superspeed – put it this way, when I saw the video I couldn’t tell it was moving! It has a circular shape, and each ‘pod’ lies on top of one another. As the voltage is applied, liquid migrates to either side causing the ‘Donut’ shape. One improved function is the smoothness of motion. The mechanics allows for great control, helpful for picking up delicate objects. If this doesn’t show elegance, I don’t know what does! After seeing this photo, my thought was that if this is simple HASEL technologies, surely it can be developed for both everyday and professional use? Not only improving mental health but broadening delicate skills such as chess! I don’t see the harm in trying to improve already invented prosthetic designs! And it gets better! The use of the thermoplastic polymers for the bags provides a low-cost production alternative to current prosthetic materials such as carbon fibre which, although durable, are extremely stiff. (Rothemund et al., 2020). Of course, with every invention, there are ALWAYS drawbacks, especially one with increasing pressures to be ‘perfect’ in today’s research era. One is the lack of temperature resistance. My proposal is to add a thin heat-resistant film, to prevent it becoming rigid whilst also becoming durable. Incorporating outer metal gratings for flexibility would allow contraction and protection. This increases sustainability of the HASEL, whilst maintaining the excellence of mechanisms intact. The hope is that HASEL will lend a helping hand to those who need it!

References: Rothemund, P., Kellaris, N., Mitchell, S.K., Acome, E. and Keplinger, C. (2020). HASEL Artificial Muscles for a New Generation of Lifelike Robots—Recent Progress and Future Opportunities. Advanced Materials, 33(19), p.2003375. doi:https://doi.org/10.1002/adma.202003375.