Engineering Bronchial Tissue through the use of Scaffolds to Treat Asthma

So what is Asthma?

Asthma is a common lung condition that causes occasional breathing difficulties. Symptoms include wheezing, a tight-feeling chest, breathlessness and coughing. During an asthma attack, airways become inflamed and the walls of the bronchi constrict, as you can see in the image below. This reduces airflow into the alveoli.

Triggers include infections, allergies, pollution and exercise, but attacks can also occur randomly, which is what I personally tend to find. Asthma affects more than 300 million people world-wide, so finding a cure is essential.

So what is Tissue Engineering?

Tissue engineering refers to the assembly of functional constructs that restore, maintain, or improve damaged tissues or whole organs. In this process, cells are selected, cultured and proliferated. For cells to proliferate, a scaffold is required. A large variety of cells are used for regenerative tissue engineering. These include:

• Allogenic cells = cells harvested from other individuals of the same species, including embryonic and mesenchymal stem cells.
• Autologous cells = cells harvested from the patient and reintroduced in a secondary site.

Tissue engineering in Asthma

Majority of bronchial tissue engineering studies have involved autologous and allogenic cells, including the use of human bronchial epithelial cells (HBECs) and human bronchial fibroblastic cells (HBFCs). The earliest study of this took place in 1999, where Zhang et al., seeded HBECs into a collagen-scaffold gel after HBFCs were incorporated, resulting in a tissue-engineered bronchial mucosa. This scientific success has lead to the continued study of bronchial disorders such as asthma.

Collagen – the best scaffold?

The role of scaffolds in bronchial tissue engineering is to provide an environment that resembles a native extracellular matrix, promoting proliferation and differentiation. When selecting the material for a bronchial scaffold, biocompatibility and strength must be considered.

Collagen is one of the most abundant structural proteins within tissues, offering high-strength, biocompatibility and even promoting cell proliferation. Even its fibre-structure is ideal -trapping growth factors and allowing HBECs to migrate and attach on the surface, hence allowing visualization under a microscope and study of bronchial disorders. Perfect, right?

Not quite… Collagen as a scaffold has limitations. Often extracted from animal tissues such as pigs or cows, collagen has poor immunogenic properties, posing a risk of carrying diseases.Therefore, collagen must be combined with immunosuppressants which increases cost. This use of animals also creates ethical and religious debate which I worry may limit the demographic that this innovation could target.

The Future

Despite these limitations, the use of bronchial tissue engineering should not be underestimated. I believe tissue-engineered bronchial mucosa acts as an effective three-dimensional model for the further study of this disorder and paves the way for the development of future effective therapeutic interventions, offering hope to millions of people world-wide, including myself.

If, like me, you feel inspired by this, check out Dr Kotton’s current and ongoing research into “rebuilding lungs“. I’m excited to see how this progresses, perhaps making use of tissue-engineered bronchial mucosa as a combined model. The future of asthma treatment looks bright.

Links/Sources:

• https://www.sciencedirect.com/science/article/pii/S0091674901404192
• https://utswmed.org/medblog/pediatric-asthma-tips-parents/
• https://www.nhs.uk/conditions/asthma/
• https://www.hse.gov.uk/asthma/lungs.htm#:~:text=Cross%2Dsection%20of%20normal%20bronchiole,actually%20block%20the%20smaller%20airways.
• https://cks.nice.org.uk/topics/asthma/background-information/prevalence/
• https://www.nibib.nih.gov/science-education/science-topics/tissue-engineering-and-regenerative-medicine#:~:text=The%20goal%20of%20tissue%20engineering,limited%20use%20in%20human%20patients.
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475566/
• https://www.sciencedirect.com/science/article/pii/B9780081025611000166
• https://www.biolinscientific.com/blog/what-is-biocompatibility
• https://www.medicalnewstoday.com/articles/vegan-collagen
• https://mokosh.com.au/blogs/blog/the-ethics-of-collagen-supplements#:~:text=A%20significant%20concern%20around%20using,a%20potentially%20less%20controversial%20source.
• https://www.anec.org/en/structure-of-collagen.htm
• https://pubmed.ncbi.nlm.nih.gov/16024520/#:~:text=The%20bronchial%20mucosa%20contributes%20to,membrane%20progressively%20unfold%20on%20inflation.
• https://www.bu.edu/articles/2023/stem-cell-therapy-lung-health-and-disease/

Approximately 45% of the mass of the human adult body is muscle tissue.

Serge Ostrovidov, PhD et al.

Muscles are critical in locomotion, prehension, mastication, ocular movement, and other dynamic activities such as body metabolic regulation. Myopathy, traumatic injury, aggressive malignant tumour extraction, and muscular denervation are the most prevalent clinical indications for therapeutical or cosmetic reconstructive muscle surgery. There are three types of muscle tissue: smooth muscles in the stomach and intestines, cardiac muscle in the heart, and skeletal muscle throughout the body. Skeletal muscle, which we will focus on in this blog, majorly consists of myocytes, the multinucleated contractile muscle fibres.

Methodology of SMTE

While Skeletal muscle tissue engineering (SMTE) has been introduced to the world of biomedical engineering for more than two decades, it remains a significant challenge, with numerous techniques being developed constantly to accomplish this.

The muscle cells are first isolated from the patient or a donor, followed by culturing, where the cells effectively differentiate and develop in the nutrition-rich medium. The muscle tissue is then generated in three methods, which form different specialized muscle cells: myotube formation under controlled topography, cell sheet formation with a hydrogel matrix, and muscle bundle formation. The well-developed and functional tissue is then transplanted back to the patient.

Limitations

This is the traditional way of engineering skeletal muscle tissue, but it still faces some limitations. Though cells could be isolated from the patient, the tissues generated from a donor could trigger immune responses in the recipient’s body, causing rejection and the necessity for immunosuppressive drugs. These medications come with their own risk, like increased susceptibility to infections and organ damage. Moreover, traditional tissue engineering often focuses on preparing damaged muscle tissue rather than promoting regeneration. Thus, the regenerative potential of the SMTE tissue may be insufficient to restore full muscle function, especially in cases of extensive injury or degeneration quantitatively and qualitatively due to ageing. On the other hand, ensuring the long-term functionality of transplanted muscle tissue is also a significant challenge. Without adequate vascularization and support structures, it may encounter degradation or necrosis over time, leading to repeated interventions.

3D Print Muscle Tissue

I came across a piece of news published in 2023 written by Michael M., mentioning the researchers at the Terasaki Institute for Biomedical Innovation have developed a fascinating new technology of 3D printing skeletal muscle tissues with bioink invented by the researchers, which could mimic the natural muscle formation.

The science of muscle 3D printing

The three parts of the bioink are polylactic acid (PLGA) microparticles, myoblast cells, and a hydrogel based on gelatin. The PLGA microparticles sustainably release growth factor-1 (IGF-1), an insulin-like hormone that’s necessary for healthy bone and tissue growth. The production process of muscle tissue is more complex than it looks. Myoblast cells were deemed viable three days after printing and successfully developed into complete synthetic muscle tissue over the next ten days, eventually contracting on their own, just like normal muscle tissues! In order to determine if the cultured tissue was viable in living organisms, the tissue was implanted into mice. The researchers were then able to confirm that the cultured tissue was successfully accepted by the body and combined with the existing muscle tissues.

Summary

The ability to 3D print muscle tissue represents a significant advance in medicine. Using this technology, muscle mass replacement could be revolutionized by mimicking the natural process of muscle development. Prior to the possibility of treating humans, further clinical studies and testing will be necessary to confirm the safety of this process before the possibility of treating humans. What’s for sure, however, is that 3D printing muscle tissue has a highly promising future in medicine. I, as a biomedical science student, am also looking forward to the further development of skeletal muscle engineering.

References:

1. Ostrovidov, S., PhD et al. (2014). Skeletal Muscle Tissue Engineering: Methods to Form Skeletal Myotubes and Their Applications. Tissue Engineering Part B Review, 20(5), pp. 403-436. doi: 10.1089/ten.teb.2013.0534

Our lecture surrounding ethical dilemmas within the scientific community has really stuck in my brain. Ultimately everyone views situations differently due to individual moral compasses. It also highlighted a key argument: what do you do with good data from bad studies? During the lecture, I concluded that ignoring the data doesn’t undo the crimes committed however it could lead to advances in the medical and scientific field. To see if others shared my views I googled, “unethical studies that generated good data”.

My research revealed it was only in 1945 during the Nuremberg trials that there was an ethical awakening due to prisoner exploitation within concentration camps for medical research. This established the Nuremburg code, which set out to prevent such atrocities from happening again. Unfortunately, studies were conducted before these laws or by people who have no regard for ethical laws now.

Henrietta Lacks

The Henrietta Lacks study is a poignant example of this moral dilemma. Lacks, was in hospital with cervical cancer, unknowingly cancer cell samples were taken and given to researchers. Experiments led to the finding of HeLa cells which became a catalyst for medical advancements in cancer treatments and immunisation.

How do HeLa cells work?

By understanding their function and immortality it is clear they’ve saved countless lives, but the unethical methods by which data was obtained has resulted in controversy.

The lack of consent and financial restitution towards the family outline the ethical complexities of using this data. Surprisingly, Lacks family have started a movement  #HeLa100, promoting the use of HeLa cells, and wish for her legacy to continue. Arguably, there is now familial consent so can the data be classed as ethically sound?

He Jiankui

The He Jiankui gene editing study also interested me, as unlike Henrietta’s story this is more recent, 2018. Jiankui lead unauthorised experimentation on embryos to try and counter HIV, by modifying embryonic genomes to become resistant against HIV – using techniques shown in the diagram. This produced potential benefits within gene editing technology. However rigorous investigations after the research was published led to this statement  “He had defied government bans and conducted the research in pursuit of personal fame and gain” resulting in a sentence of 3 years imprisonment. Fortunately the embryos in question have become three healthy children.

This creates the dilemma – can we use these techniques?

My thoughts

Upon reflection, I think both studies generated data that has led to great scientific discoveries, which fortunately haven’t had negative consequences. It is estimated that HeLa cells have gone on to save over 10 million people worldwide. I think that statement alone argues that we should be using this data even if it was obtained by unethical means. These cells have also contributed towards development of vaccines, preventing the spread of disease and minimizing impact – e.g. the COVID-19 vaccinations.

I also believe that although He Jiankui conducted an unethical study, it’s positive outcome brought about an unbelievable breakthrough in gene editing science. It could create treatments for inherited disorders, that are currently incurable.

Overall, I think the data generated from these studies has led to life changing scientific breakthroughs that if ignored could result in unnecessary deaths and stress on hospitals. But this is just my view, so I would like to put this out there what would you do with good data from bad studies – would you use it?

Can lab-grown meat be a more ethical food solution?

Recently, a number of my family became meat free. As a lover of chicken nuggets, I was surprised by this, with the scientist in me concerned about the potential drop of protein ingestion. Naturally I was curious about this change, and subsequently gained understanding of how detrimental conventional meat farming is to the environment, the harm to the animals and the cost involved. I recently attended a lecture about tissue engineering and was made aware about how it could be used to grow meat in a laboratory and did more research to determine whether this would be an improved method of meat farming and I believe it is. 

The Science of Tissue Engineering

Tissues are made up of cells and an extracellular matrix ; this is anything in a tissue not located inside a cell and is produced by the cells themselves. Tissue engineering involves combining the living component of tissues (cells)  with a scaffolding material for structure and then placing it in a growth media for development. There are a range of scaffolding materials available some are biodegradable and some are not.

Cooking 101 : How to grow your own meat

Meat sold in stores is mostly muscle tissue from the animal it’s harvested from with some fat tissue so could be grown in a tissue engineering lab.  

1. The process begins by extracting cells from an animal, a small sample is taken from an animal under anaesthesia by a trained professional. 
2. Myosatellite cells (multipoint muscle stem cells) can be extracted and placed in bioreactors with a growth medium that mimics the natural environment the cells would experience as part of an animal (access to oxygen, nutrients and minerals need for differentiation/growth).
3. Changes in the media composition ,usually cued by addition or activation of the scaffolding material, initiates the differentiation of the muscle stem cells allowing formation of skeletal muscle cells, fat cells and connective tissue.
4. The differentiated cells are harvested, prepared and packaged before being sent off to be sold in stores.

Certain variables like the size of the meat being produced, the growth medium used, the number of stem cells you start with determines the time it takes for this process to occur. Current methods place the timeline between 2-8 weeks which is much faster than rearing an animal from birth for their meat.

Benefits, Limitations and Ethics

Watch this short video to see the benefits of the production process of lab cultivated meat environmentally, to animal welfare and eventually financially.

The main limitations of lab grown meat include:

• Scaffolding materials are unable to supply oxygen and nutrients to larger tissues like muscle
• Developing these technologies will be expensive so first generation products might not be affordable to the average household

The main ethical implications are:

• Animals must still undergo a procedure to extract the cells
• If the scaffolding material cannot be removed from the end product a hybrid product will be formed as there are no animal based scaffolds currently available.

My Opinion

However, I believe that like me, when people become more aware about the negative effects that large cattle farms have on the environment, how much more cost effective meat production could be as technology advances and ,the biggest reason, that no more animals have to die or be raised solely to be eaten, lab grown meat will rise in popularity and will be properly invested in as an industry.

During our sensor lectors, the concept of an artificial pancreas was discussed. This stood out to me as my stepmother has diabetes and I had never really considered how having this actually affected her life. It also made me aware that I didn’t even know if she already used an artificial pancreas! Then through researching, I was drawn to the DIY artificial pancreas. I wanted to understand what this was and whether it was the most beneficial option in terms of cost, function and aesthetics.

Individuals with Type 1 diabetes cannot produce insulin to monitor their blood glucose levels. Instead, they inject insulin throughout the day; calculating how much is needed dependent on factors such as what they’ve consumed.

What is an artificial pancreas and how does it work?

What is a DIY artificial pancreas and how does it differ?

A DIY artificial pancreas is non-NHS funded but uses similar equipment. It uses a specific app to control your equipment which needs to be compatible with your insulin pump. Guidance is mainly provided through the diabetes community and not the NHS as they have limited knowledge on how these programs work. If you are’ techie’ then you can fine tune this program and ‘train’ the system: making this an advancement on the NHS funded system.

What are the pros and cons?

Now, there are benefits to this: insulin is given automatically when needed which can be ideal especially for young children; allowing a more stress-free experience whilst giving their parents a way to monitor their blood glucose levels throughout the day. It also removes the need to inject which can be beneficial for those who dislike needles. As mentioned, the DIY version can be ‘trained’ to your specific needs so will reduce the energy and brainpower the individual spends on calculating the correct levels. However having said that, because it is technology, this can always malfunction and if given the wrong amount of insulin, it can cause a hypo. The program also requires internet connection where you still need to input your meals as the artificial pancreas can only give basal insulin automatically. In terms of the DIY version, it can be complicated to install and needs updating regularly. Since it needs to be attached to either a belt, a belt loop or a pouch, aesthetically the insulin pump can look bulky under clothing and limit the options of available outfits an individual could wear. This could cause insecurities or just be an added inconvenience.

After both points of views it’s clear how life changing a DIY artificial pancreas can be!

Over the last decade, 3D printing technology has improved drastically, with the main focus from commercial businesses being to reduce their complexity and improve their usability. In contrast, whilst the technology in the medical industry has also improved, complexity has also increased with it. As a Biomedical Electronic Engineer, I am particularly interested in the application of 3D printing within the medical industry.

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So, what are the main applications of 3D printing in the medical industry?

Bioprinting

Bioprinting has revolutionised organ transplantation by offering a unique, custom solution. Foreign body rejection can be mitigated using the patient’s own stem cells reducing the need of further surgery. It also eliminates the sometimes agonizing wait time for an organ match – in March 2023, there were around 7000 people waiting for a replacement in the UK alone, so this issue could be avoided entirely. However, the high cost, complexity and ethical implications pose significant challenges, making it inaccessible for some individuals.

Surgery

3D printing can also be used in surgery to make custom tools for different procedures, and to aid with surgical preparation. One of the most interesting moments for me on this module was visiting the IDS building at the hospital, and learning how scans were used to create a custom hip for a lady requiring a hip replacement. This device helped the surgeons to practice the procedure, whilst also providing the patient with a safe solution. A standard operation would have been difficult and risky due to the level of bone loss; this model helped to replace necrotic (dead) tissue and also bone which had been removed from prior surgeries. After studying modules which covered topics similar to this, it was interesting to see a physical example of a hip replacement, and I found it inspiring that someone could be helped using 3D printing.

Prosthetics

Custom prosthetics can be developed to improve millions of lives – something that motivates me to pursue a career in this field. 3D printers have a massive range of flexibility when it comes to manufacturing, so different designs can be made very easily without the need of additional hardware. I am currently designing a 3D printed prosthetic hand as part of my individual project using my own FDM 3D printer. FDM (Fused Deposition Modelling) is the simplest form of 3D printing; it relies on the layering of molten thermoplastics to produce a 3D object. This project alone has illustrated to me that modern 3D printers have an extremely wide variety of uses at a relatively low cost, with further technological advancements potentially increasing the accessibility of custom prosthetics across the world, helping millions more people in the process.

I personally think that this technology will develop further to the point where any physiological issue can be resolved using something that has been 3D printed – there has been a massive advancement in this field in the last 20 years, so who knows what its capabilities could be in another 20 years!

Overall, 3D printing has provided an efficient solution to complex problems within different industries – especially the medical industry. Different printing methods have contributed to improving countless lives which has inspired many people, including myself, to develop the technology further and hopefully help many more people in the process.

Epilepsy is a chronic non-communicable disease of the brain characterised by recurrent seizures generally brought on by specific triggers. The most widely accepted description of seizures is tonic-clonic seizures, in which there are brief periods of both tonic (stiffening) and clonic (twitching/jerking) muscle activity but epileptic seizures can manifest in a variety of ways, including absence or loss of consciousness.

My brother is one of the 50 million people worldwide who suffer from this illness and over the previous six years, he has suffered from sporadic, severe tonic-clonic seizures that have irreparably damaged his shoulder, necessitating a shoulder arthroplasty. I didn’t consider the long-term effects of epilepsy as a neurological condition on wider parts of the body until my brother experienced recurring seizures that damaged his shoulder. Upon further research, I have found that shoulder instability is a widely experienced deficit in epileptic patients due to the common risk of dislocation in a tonic-clonic state but can also be caused by the lack of education in seizure management, e.g. restraining someone’s arms during convulsions.

The most common type of instability seen in patients suffering from convulsive seizure conditions is a posterior dislocation alongside skeletal lesions, mainly reverse Hill-Sachs lesions. If the Hill-Sachs lesion covers more than 20% of the humerus head then a surgical procedure is the needed modality of treatment such as a remplissage procedure to fill the indent caused by the lesion or a bone graft to insert additional tissue into the humerus. However if it is not possible to reach clinically defined stability with other procedures or there is simply too much damage to the humerus, scapula and other bone tissues then a full or partial shoulder replacement will be considered. Reverse shoulder replacements are considered when considerable damage has occurred in the rotator cuff so that the replacement will rely on the deltoid to move the arm instead.

Some considerations to be addressed when importing an artificial shoulder into an epileptic patient range from seizure control during and post-operation, material compatibility, fracture and wear resistance and potential reoperation risks. In my opinion, the most important qualities needed from the shoulder replacement are high fracture and wear resistance due to the unpredictable nature of seizures making epileptic patients more prone to traumatic injuries. Furthermore, material compatibility is vital in ensuring the arthroplasty fully integrates with the patient and certifies a low risk of shifting during a convulsive seizure.

Material compatibility and fracture and wear-resistance are two factors that seem to work on a pivot as upon further research it seems that materials such as Ti-6Al-4V (titanium aluminium valium) alloys are less wear-resistant but are very effective in osteointegration and hold good osteoconduction properties. Up-and-coming research into joint replacements has already seen impressive benefits in using ceramic and pyrolytic carbons as alternative bearing materials and chemical modifications to polyethelene such as cross-linking, minimizing oxidation, and vitamin E impregnation, have been developed to minimize wear. Improving the bioactivity of orthopedic materials such as mechanically reinforced UHMWPE has been shown as successful and a great candidate to be used for bone replacements (Senra et Al, 2020).

To conclude, shoulder arthroplasty is a safe and beneficial surgical treatment for recurrent shoulder dislocation in seizure-prone epileptic patients (Austin et al, 2023). Upon asking my brother, he has seen a massive improvement in his quality of life thanks to the replacement surgery as he now has a better range of motion, reduced pain and increased stability without having to worry about complications if he dislocates his shoulder during a future seizure. I’d never considered the benefits of replacement body parts, such as shoulders, for patients suffering from neurological conditions but now I can see what is achievable in improving their quality of life when dealing with a debilitating disorder such as epilepsy.

Sources:

https://www.who.int/news-room/fact-sheets/detail/epilepsy

https://www.sciencedirect.com/science/article/pii/S1045452722000803#:~:text=The%20safety%20of%20shoulder%20arthroplasty,cuff%20disruption%2C%20or%20implant%20failure.

https://www.sciencedirect.com/science/article/pii/S1058274602000228?via%3Dihub#bib20

https://my.clevelandclinic.org/health/diseases/24304-hill-sachs-lesion#management-and-treatment

https://pubmed.ncbi.nlm.nih.gov/32890047/#:~:text=The%202%20main%20metal%20alloys,improved%20osseointegration%20and%20osteoconduction%20properties.

A backstory…

When I was young, my Granny lost her arm to amputation. Since then, I’ve watched her struggle, relearn, and grasp the basic skills to be able to live an almost normal life again. I’ve always been proud of how she reshaped her life, and since mine revolves so much around sports, I couldn’t imagine coping with a lost limb. This is until I met South African elite para-triathlete, Mhlengi Gwala. He told me about his backstory how he tragically lost his leg and the work he’s done to get to where he is today. I instantly became fascinated with the rehabilitation he endured so I explored deeper into it.

The Road to Recovery

Prediction times for the return to sport after amputation were studied by Matthews et al. I learnt that it’s hard to give an exact period on how long amputation recovery will take, let alone getting back into sports. This is due to factors like what limb was amputated, stump length, the cause, and sport. Think about when you were a baby, you learnt to walk before you learnt to run. The same idea applies to athletes with leg amputations. According to Pam Health, there’re 3 main components to the healing process:

1. Physical therapy and rehabilitation

During surgery, all unwanted parts of the bone and muscles are removed, and the healthy muscle is reattached to the remaining bone. The amputees need to rebuild strength and flexibility within these muscles and learn to use their prosthetic (if one’s needed) with the help of physiotherapists and rehabilitation teams. 

2. Managing the risk of complications

Commonly, amputees will run into complications during recovery. These include things like infection, stump pain, phantom pain, etc, which require additional treatment.   

3. Gaining mobility and independence

Lastly, when the amputee becomes confident enough with the new adjustments, they’re able to live independently. In Mhlengi’s case, he knew that he wanted to get back to racing, and I believe that having something to work towards helped him through recovery and to become a new upcoming para-triathlete.

Is the Price of Sporting Prosthetics Fair?

I mentioned that I was studying biomedical engineering to Mhlengi, who replied “You’re going to be rich, these aren’t cheap”. According to Alan Hutchison, a leg prosthetic can cost up to $60,000. Shocked, I researched why, looking specifically at running prosthetics. A para-athlete with a leg amputation will generally have two different prosthetics because when running or jumping, you’re applying a larger impact force onto your legs. The sporting prosthetic must be able to withstand this, therefore it’s constructed into a curve using carbon fibre and custom-made to fit the stump depending on size, shape, and whether the amputation occurred above or below the knee. Taking these into account, it makes sense why the prosthetic is expensive but it’s still debatable whether this price is too high, especially for someone who’s already faced tragedy. Luckily for Mhlengi, he had many supporters on his side who helped him get to where he is today. 

Summary

I’ve always respected para-athletes for what they do, but I’ve never appreciated the process they endure to be able to do these things. Through this research, I’ve realised that “getting back on your feet” takes a lot of patience, not only through rehab but also in acquiring the prosthetic to begin with, however, it’s amazing what can be achieved when you’re driven by the things you love.

Imagine a world where baldness and hair loss is no longer a source of insecurity; a world where those suffering from these can regain their confidence and self-esteem. 

Hair bioprinting isn’t just about aesthetics. It holds promise for treating various hair and scalp-related conditions, such as alopecia, a condition that affects millions worldwide. By harnessing the regenerative potential of cells, this technology may offer hope to those who have been struggling with hair loss for years.

In one specific study, the replication of in-vivo tissue configurations and microenvironments like hair follicle germs has been studied to prepare tissue grafts for hair regenerative medicine. This study suggests an approach for the scalable and automated preparation of highly hair-inductive tissue grafts using a bioprinter.

Hair follicle morphogenesis initiates with the formation of a primordium composed of mesenchymal and epithelial cells, instigating tissue development. Distinguished from other organs, the hair follicle generates the hair follicle germ (HFG) at regular intervals postnatally, perpetually renewing throughout life. In the pursuit of advancing hair regenerative medicine, diverse methodologies have been devised for engineering HFG-like grafts, with one of the most sophisticated methods being the use of bioengineered HFGs. This method entails the compartmentalization of mesenchymal and epithelial cell aggregates to elicit interactions, thereby fostering efficient hair follicle regeneration and establishment of connections with host arrector pili, nerve fibers, and recurring hair cycles upon transplantation. However, this approach may be challenging to scale up to the human setting due to laborious manual preparation steps, especially considering the need for thousands of tissue grafts for a single patient. So, there exists a need for a scalable, highly hair-inductive, and preferably automated approach for HFG preparation.

Exploration into scalable methodologies for preparing mesenchymal and epithelial aggregates has predominantly centered around the concept of cell self-organization. Among these approaches, one notable method entails the seeding of a blend of these cellular components onto a flat substrate. This process gives rise to the formation of spherical aggregates characterized by a mesenchymal core enveloped by an epithelial shell. However, while promising, this technique has encountered a notable challenge: the wide distribution of spheroid sizes. This variability in size could potentially lead to unpredictable outcomes in terms of hair-inducing functionalities. It’s been observed that the size of these spheroids correlates with the number of hairs generated, hinting at the intricacies of the relationship between structure and function in tissue engineering endeavors.

Pairs of collagen droplets housing mouse embryonic mesenchymal and epithelial cells were meticulously positioned adjacent to each other and sequentially underwent gelation. In the subsequent suspension culture, the microgel beads spontaneously contracted, thereby enriching the density of collagen and cells after three days of culture. The contracted microgel beads were termed HMGs or hair microgels. To evaluate their hair-inducing potential, they were transplanted into the dorsal skin of nude mice. gHMGs were fabricated in the same manner, but by placing pairs of collagen droplets on aligned surgical suture guides. The effects of the guides were examined after transplantation into the nude mice.

Fast forward to 2017, where the beauty giant L’Oréal made headlines by partnering with the biotech firm Poietis, renowned for its expertise in crafting 3D models of human tissues, to embark on the groundbreaking endeavor of bioprinting hair follicles. Hair bioprinting is a prime example of interdisciplinary collaboration. It brings together experts from fields like biology, engineering, and medicine, all working together to unlock the potential of this cutting-edge technology.

While the prospect of bioprinting hair follicles holds great promise, further refinement of the process is required and extensive research is needed to ensure its safety and long-term effectiveness. On one hand, the idea of being able to customize hair growth feels like a step towards empowerment, a chance to redefine our appearance according to our own desires. But on the other hand, it raises questions regarding the accessibility and affordability of this technology to a broader demographic that must be addressed, underscoring the importance of making cutting-edge advancements in regenerative medicine inclusive and sustainable. Who will have access to this technology? Will it be reserved for the privileged few, widening the gap between those with the finance and those who don’t? Or will it be made accessible to all, ensuring that advancements in science benefit everyone? It’s not just about innovation; it’s about equity and justice. As we navigate the uncharted territory of bioprinting, we must ensure that it’s not just a luxury for the elite, but a tool for empowerment and inclusivity. Only then can we truly harness its transformative potential for the betterment of all.

Despite 100,000 people experiencing a stroke each year in the UK alone and statistically one in four people over the age of 25 having a stroke in their lifetime, there is currently no clinically effective treatment available to reverse the brain damage caused by strokes.

Last summer my mother had a stroke. Not long ago, this sentence filled me with both sadness and fear of what this actually meant, something not only I was feeling. The road to recovery for stroke patients can be steep and unknown due to the short time treatment can be given within, and the limited options currently available. This led my opinion of stroke research to be pretty negative and views of progress to be at a standstill.

A stroke is a life-threatening condition that occurs when the blood supply to parts of the brain is cut off, this lack of blood means no oxygen and nutrients can reach the brain leading to cell death. Strokes are medical emergencies, however, if caught early and treated patients are more likely to make a full recovery with almost no permanent disabilities.

The current treatments available in the UK depend on whether the stroke was ischemic; when blood supply to a region of the brain is blocked, or haemorrhagic; when there is excessive bleeding in parts of the brain. Other factors also include the time since the symptoms began and the presence of any other medical conditions.

Roughly 87% of all strokes are ischemic!

Treatments for an ischemic stroke include both medical procedures and medications. Mainly a medicine called a tissue plasminogen activator is used, which breaks up the blood clots that are restricting flow to the brain.

Whereas, for a haemorrhagic stroke blood pressure medicines are normally prescribed to lower the pressure on blood vessels alongside some form of procedure such as aneurysm clipping, coil embolisation, draining excess fluid and surgery to temporarily remove part of the skull.

Although there are multiple treatments available none are specifically tailored to each patient and can specifically target damaged areas regardless of the time taken to receive care. So, what if there was a way to precisely target damage no matter how long after the initial stroke?

A New Potential Delivery System…

Recent studies by Baker (2009) and Bible et al. (2009) aimed to develop technology for stem cell delivery to treat brain damage. They successfully attached neural stem cells to scaffold particles, optimised conditions for cell viability, determined the ideal particle size for effective delivery, and used MRI-guided implantation for precise targeting. Observations showed primitive tissue formation within seven days post-implantation, marking significant progress in developing stem cell scaffold matrices for stroke treatment. The study highlighted the potential of stem cell research to enhance transplantation viability using bio-scaffolding.

Delving into stroke research has been an eye-opening journey for me, exploring the complex world of neurological damage and potential new treatments. It’s captivating to realise the immense challenges faced by individuals like my mother and other stroke survivors including the impacts on their lives and families, all adding to the urgent need for effective treatments. Investigating the latest developments in stem cell therapy, tissue engineering, and imaging techniques has left me both impressed and inspired for the future of stroke therapeutics.