Printing New Organs: The Promise and Problems of 3D Bioprinting

Did you know that around 17 people globally die every day while waiting for a heart transplant? That means that yearly around 6200 people are unfortunately not able to receive the transplant that they need in order to survive. This alarmingly high number is due to insufficient supply of organs that are ethically sourced and meet the rigorous criteria required to be safe for donation. In developing countries, organs are also limited by logistics as they must be transported in certain temperatures and under certain conditions within a very short period of time which may not be feasible with their infrastructure. Additionally, the social stigma and fear around transplants means there are very few registered organ donors.

With ever evolving technology and innovation scientists have been able to successfully print, yes print, like a 3D printer, human tissues ranging from muscle tissue, neural tissue and cartilage all the way to a whole organ. While this is revolutionary for the future of medicine and the prolonging of human life, it also raises many scientific and ethical challenges that must be addressed before it becomes a reality.

Before we dive deeper into some concerns related to bioprinting it’s important we first understand what it is and how it works. The first step is actually designing the tissue that we want to print. Many X-rays and MRI’s are taken and every microscopic detail is analysed before being turned into a 3D model. This model is then printed row-by-row, in a layer-like fashion, before being processed further to ensure the layers can work together as a whole. When printing different tissues we need to consider the different properties that we need to capture so that we can pick the right biomaterials to construct them. Some considerations include the strength, porousity, stability and immunogenicity to ensure that the tissue functions properly without disrupting the body. 

Essentially, there are 3 main components to bioprinting: Bio-ink, Blueprint & the Bioprinter. The bio-ink is the material that we choose based on the function of the tissue. For example, hyaluronic acid can be used in combination with other polymers to change their viscosity and adapt their properties - in some cases increasing the compatibility and strength of the resulting polymer. The blueprint is the idea mentioned above, where the tissue that we want to replicate is carefully analysed and reconstructed into a 3D model replica which can be printed. Finally, the bioprinter is the machine that actually deposits the bioink in the exact pattern that is required.

There are many examples of bioprinting which you may not realise have already been implemented, even though the printing of whole organs and complex tissue systems is relatively new and still developing. Most notably these include: crowns, fillings and implants in dentistry and the printing of prosthetics, hearing aids, screws and plates in orthopedics. 

Bio printing has a lot of potential to significantly reduce the shortage of organs available for transplantation and reduce the number of people on increasingly growing organ donor waitlists. Perhaps one of the most useful properties of bioprinting is the level of individual personalisation that allows us to create the ‘perfect’ implant for that specific patient depending on their anatomy and medical condition. This significantly reduces the risk of post-operative complications such as rejection considering the materials used should ideally be highly compatible with the patient’s body. Furthermore, the developments in this field reduce the need for animal testing of emerging drugs and new research as this can all be tested on lab-grown tissues. Aside from the ethical benefit, this also provides more accurate data as these lab-grown organs more closely resemble the human body and the way in which it reacts to different substances. Another benefit of bioprinting is the ability to repair defective or diseased tissues with healthy copies that provide the same function. This includes the regeneration of skin for burn victims or the growth of bones for serious injuries or bone diseases. Some recent breakthroughs include: a patch of heart tissue (created by the RegenBell research team) that can survive and beat correctly for at least a month after implantation and the first heart mini-organ’ (created by Stanford researchers) that actually resembles an early stage heart with all the corresponding cell types.

Despite these breakthroughs and constant developments of new methods there are many challenges that must still be overcome before a fully functioning organ can be produced. 

One of the most complex but important parts of an organ to replicate is the network of blood vessels within it that supply oxygen and other molecules to the tissues and allow it to survive. The developments of organoids (mini-organs) stemmed from the challenge of overcoming this. Organoids are made up of very few cell so can take in oxygen and other substances from their environment by diffusion, osmosis and active transport. However, this really limits the size to which these organoids can grow because as they grow larger, the cells towards the center begin to die due to insufficient oxygen levels. Many researches have tried to overcome this but the complexity and vast amount of cells required to reconstruct a blood vessel network is immense. As I mentioned earlier, some researchers at Stanford have had some success in replicating blood vessels that resemble the capillaries of the heart in their organoid. They were able to form cardiomyocytes and smooth muscle cells on the inside and an outer layer of endothelial cells which are characteristic or cardiac capillaries. Although this is a massive development towards growing full size organs with a blood supply, there are many setbacks that are inevitable with the realisation of a working blood vessel network. 

2 week old heart organoid grown by Stanford researchers - cardiomyocytes (green), smooth muscle cells (white) surrounded by endothelial cells (magenta) forming a network of realistic blood vessels.

Another key challenge is prolonging the longevity and functionality of these bioprinted tissues. Printed tissues often deteriorate in the body and don’t last as long as natural tissues or donor organs. The key challenge with the tissues such as printed patches of heart tissue is the inability to recreate the myocardium in full complexity and with a network of blood vessels. This means not enough blood and nutrients reach the tissue which doesn’t allow the tissue to properly mature causing it to develop fibrosis and inevitably die. This option isn’t suitable as a long-term solution and is therefore not a feasible option for implantation into patients. However, with the new layer-by-layer printing technique, a patch of heart tissue (created by the RegenBell research team) was able to have a network of blood vessels printed within it allowing it to survive and beat for a month. This new technique and development in research is sure to progress and inspire future lab-grown organs.

A 3D render from the RegenBell published article 2 weeks after implant - the cardiomyocytes are in green and the blood vessels are in red.

With the development of bioprinting also comes a plethora of ethical, accessibility and regulatory concerns posing questions such as: who technically owns lab-grown organs? Should people be allowed to ‘upgrade’ their bodies? Could this new technology widen the inequality between the rich and poorer who may be unable to afford it? How do we ensure safety and quality control for living parts?

As far as ownership of these organs and the idea of ‘upgrading’ our bodies goes, it is very similar and directly links into the existing ethical concerns of prosthetics and how they may be surpassing our natural abilities. Although valid questions, I personally feel like in the future we will have different committees who oversee and regulate these concerns as well as push to maintain the quality of these lab-grown tissues. Although these are very new and complex techniques, people shouldn’t be scared of them as they will have to go through rigorous testing and many clinical trials before they are able to be mass-produced and implemented in modern medicine.

Despite many setbacks and challenges that need to be overcome, this industry is constantly expanding and finding new ways to push the limits. The future of this industry likely combines elements from AI, stem cell biology and collaborations with engineers and medical professionals to ultimately create viable organs which can meet current demand. Although printing full organs is likely still decades away, the printing of tissues is already undergoing medical trials, where if successful, may soon be widely implemented. Overall, 3D bioprinting in itself shows that the future of medicine will require the collaboration and joint efforts between many different fields and professions to fully capture and replicate the complicated essence of human anatomy.

Sources:

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