No matter what era we are in, humanity’s collective imagination of what the future would look like, has one clear pattern.
“The future we all imagine, and our past counterparts too, is one with stunning medical advancements. Where people would succumb to horrible disease and where illness is nothing more than a nightmare.”
And while we cannot discredit the billions of hours and dollars, we have spent to making this dream come true — and the breakthroughs we have had along the way, here in 2022 the fact is there is still another important stronghold of medicine that humanity has not been able to conquer.
When we say that imitation is the finest form of flattery, nowhere has that been as true as in the field of science. Some of our finest inventions have come from the observation and mimicry of the nature that surrounds us. And when it comes to medicine, mimicry of nature, at least to the fullest extent is very difficult achieve.
Making artificial tissue that acts and is nondistinctive from biologically produced tissue is the bastion many have been working to solve. And given that in the medical context, the imitation of a biological force means replicating the various relationships between different (and often unknown) factors, we set the stage for why it hasn’t been done yet.
Artificial Tissue 101
When we think of bones, skin or anything else in the body, we are actually referring to a bunch of cells that create these superstructures. When these cells come together and create functional structures that have a certain purpose, we call them tissue.
Right now, tissue can only be formed naturally within a body and even the repairs done to the tissue (e.g. shedding skin) is constrained to what the body can and is able to do.
All of that is a naturally a huge constraint in medicine as if something goes wrong with the tissue our only recourse to restoring the tissue to its functional state, is to move a viable counterpart from somewhere else (such as grafting or transplants) or try to promote the tissue to naturally repair (such as some drugs).
The crux of the problem lies in the inefficiencies present in running our healthcare in this way. People who need tissue can’t find right matches, supply sometimes cannot meet the demand and there are inconsistencies in replacements. By extension it is slow and with an unclear outcome by the end.
The solution to this problem is artificial tissue because it is something that can get matching tissue to the right people, at the right time, consistently. All of this can be distilled to the fact that artificial tissue is only the means of achieving the same end result. It will still be a structure made of viable and functional cells and ideally is identical to tissue made naturally.
If we have theoretical goal of having to create artificial tissue that is identical to that of nature, the next logical question would be how to do this. Afterall, cells aren’t just Legos that you can stick together and call it a day.
In this case, because precision is key, one of the most unique but promising method to making artificial tissue, is 3D bioprinting. This comes from the same idea as normal additive 3D Printing where material is shot out of a mechanism to a set of predetermined instructions, to great some 3D and tangible product at the end.
3D Bioprinting is not dissimilar where the idea is to spray cells out of a nozzle and build up a 3D structure (presumably a tissue). However, cells are living things not just random liquid plastic, which means much more care is required to do this process correctly.
The Cell: A Bioprinter's biggest challenge
Tissue and certainly cells have been purpose built to be part of a larger system that actually allows it to thrive. This fundamentally clashes with what 3D Bioprinting is, which is isolating a group of cells to create a structure. Given that this is an unignorable component of cells, in order for bioprinting to be effective, we must also mimic an environment that meets the needs of the cell.
This is a key challenge where factors like energy resources, oxygen, fluids, electrical balance, thermal needs and ph all matter to a very tight degree.
The current precedent to facing this challenge is putting the cells in “bioink.” This is a medium that's designed to give all the nourishment that a cell requires to function correctly. However, when building more complex structures this bioink is not sufficient to keep the whole cell structure viable.
Additionally due to the nature of some of the cells and their structures, it is more effective (or only possible) to allow cells to grow on their own, instead of being mechanically placed. This means additional stipulations are required.
This is the current state of bioprinting, although theoretically possible and demonstrated in some places, structural and environmental limitations need more research for real tissue to be viable.
A Silver Bullet for 3D Bioprinting?
With a problem of such great impact to society it is a given that many solutions, ideas and possibilities are being revisited to solve the problem. However, amongst the various propositions, one solution that seems to have a lot of promise and growth, are bioprinting scaffolds.
Scaffolds when something is 3D printed makes perfect sense. You need something for your materials to be placed on and rested. But at the same time, it cannot be permanent because that interferes with whatever its purpose may be. The additional benefit in this circumstance is that scaffolds can provide the additional stability that is desperately needed for cell viability.
ECM: The Scaffold Promise
Scaffolds are so influential because they are able to simulate the extracellular matrix (ECM) of cell. This is extremally ideal because as the complexity of the tissue increases, the less bioink on its own can help the cell. The ECM specifically helps in tissue regeneration by providing the correct environment, enzymes and interactions that are necessary to promote growth. Additionally, it has the capability to promote structural change and stability.
This is a key finding because, as discussed earlier (and especially with more difficult-to-make tissue), it is simply not feasible to place every single cell. This means when it comes to tissue that require cell-based growth, an ECM increases its feasibility greatly.
Based on these factors, there is an area of research dedicated to finding materials that can act as a scaffold for printed tissue. These materials ideally need to also be biodegradable to be a suitable candidate. This is because given it is a proxy ECM, it cannot be removed until it is ready for use (likely in a natural ECM within a body).
While we only explored one challenge facing artificial tissue, in depth, there are other benefits to using a specially designed scaffold.
This is because the other major problem facing artificial tissue is standardization and consistency. The has to do with how the modelling of the tissue is done before production (similar to a CAD for 3D printers). Scaffolds can be extremally beneficial because it can provide more flexibility to designers and the cells themselves.
A Promising Future
Tissue printing is undeniably still in its infancy. Yet it has shown so much growth and prospects for a quality future to be ignored. Artificial tissue provides so much more flexibility to the medical community not only with treatment but also in areas like drug testing, biological interactions and disease research.
We are at the stage of artificial tissue where there are proofs of concepts which then require gradual changes and tweaks to become feasible. Part of that is the introduction and testing of scaffolds that have shown immense promise and growth as an option.
Organovo is an example of one of these companies that have successfully engineered aspects of kidneys, livers and skin. These companies already utilize scaffolds, but only for the “simpler” tissue described above.
Personally, I think that the future promising, not only because of the results we can see here, but because this is the result of an ages long dream of what medicine should look like.
Now it's off to making stuff!