3-D BIOPRINTING: Tissue Regeneration
Additive manufacturing or 3-D Bioprinting has come a long way, from the screens of our television to a more tangible reality. While organs may be a little farther in the future, tissue printing is within the realm of possibilities of the present. 3D bioprinting can revolutionize tissue engineering as its objective is to restore damaged tissues by imitating the natural cellular structure and creating precise geometrical models using biomaterials and cells. Additionally, since additive manufacturing uses a top-down approach, it deposits the biomaterials layer by layer, in a specific pattern to regain the normal structure and function of complex tissues. To put it in layman’s terms, it will soon be possible to “print” your tissue, making the requirement of a transplant unnecessary.
I’d like to take you through a few examples of 3D bioprinting, going through the problems and the solutions that were discovered while highlighting the applications of the same.
3D tissue constructs for skin regeneration
Many 3D bioprinting techniques have been put forward such as inkjet, extrusion or laser-induced forward transfer (LIFT) printing. All of these techniques have been shown to create complex printed structures but each of them have their own limitations. For example, with Inkjet printing there comes the risk of cell lysis in high-frequency piezoelectric actuation. Essentially, it translates to, when the bio-ink is ejected to print the object, it could destroy or disintegrate the cell. When it comes to extrusion, there is a limited range of viscosities that can be printed (approximately 1 to 300mPas).
3D printed skin tissue, a promising first step
To combat these shortcomings, research has discovered DLP (Digital Light Processing) — based 3D printing. It has the solution to all of the above limitations with better printing speeds, extremely precise microscale resolution and maintaining cell viability. Pair this printing technique with a biomimetic bio-ink composed of photopolymers (light-sensitive resins that solidify on exposure to UV radiation) like gelatin methacrylate (GelMA) and Niobium-reinforced Hydroxyapatite (HA-NB) and it ticks off all the boxes, be it biocompatibility, good printability, similarity to the extracellular matrix(ECM) or promoting cell migration and proliferation. It may seem like a lot of biochemistry to many but I’d like to highlight that this can be used to fabricate functional living skin. The study results depicted that this bioprinted skin promoted wound healing in a pig model. In time, it could be used for human trials and potentially be a breakthrough in medical sciences.
Microdrop Printing of Hydrogel Bio-inks
An optimized 3D inkjet printing process
From this, we can see that bio-inks play a pivotal role in the creation of structures. Using 2D printing analogies, it’s similar to how there are cartridges for printers, you can’t just put any kind of ink and expect an Inkjet printer to work. Also color cartridges create various colors while printing by mixing cyan, yellow and magenta in different ratios. Similarly to replicate tissues, one must use a bio-ink of suitable constituents to get a successful output.
This is how the limitation related to 3D inkjet printing can also be resolved. Research has been done to create an optimized process to restructure alginate into a tissue-like microvasculature. This enables it to carry out biological functions and abide by physiological flow rates. The process involves enhancing the reaction at the single droplet level, overcoming the natural tendency of hydrogel droplets to spread and coalesce, allowing for wet droplet stacking and live cell patterning. The best part is the process can be extended to other hydrogels, making its applications in tissue engineering and regenerative medicine enormous.
Marine Biomaterial-Based Bio-inks
Graphical demonstration of manufacture of a bio-ink
Alginate and fish gelatin (f-gelatin) are also two biomaterials that have potential uses in 3D bioprinting. Alginate is derived from brown algae while f-gelatin is derived from marine resources, quite “fishy” if you ask me. As with all of the elements we have discussed earlier, f-gelatin has an Achilles heel — its mechanical properties and stability. However, for every problem, there exists a solution. In this case, f-gelatin was chemically modified to obtain a photocrosslinkable form called f-GelMA (fish Gelatin methacryloyl). This interpenetrating polymer network (IPN) hydrogel showed superior mechanical strength compared to pure alginate hydrogel, making it suitable for various tissue sizes and shapes.
As we have seen from just these few examples, the potential of 3D bioprinting using various bio-inks is nothing short of extraordinary. Additive manufacturing could potentially create adipose tissue and fabricating complex-shaped scaffolds for bone tissue engineering. Scaffolds provide a foundation which can grow cells with the help of growth factors. There are manifold applications to 3D bioprinting and innumerable ways to execute it. Once it is applied to mainstream healthcare after human trials, this could potentially disrupt the industry as a whole. It truly is an exciting future to look forward to!
References
https://www.mdpi.com/1660-3397/16/12/484
https://www.frontiersin.org/articles/10.3389/fmech.2020.589171/full
https://wyss.harvard.edu/technology/3d-bioprinting/
https://www.sciencedirect.com/science/article/abs/pii/S0142961215004998
https://www.sciencedirect.com/science/article/abs/pii/S0142961220305330
https://onlinelibrary.wiley.com/doi/abs/10.1002/adma.201102800
https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.201800050
https://onlinelibrary.wiley.com/doi/abs/10.1002/adbi.201700075
https://www.sciencedirect.com/science/article/pii/S136970211300401X
https://onlinelibrary.wiley.com/cms/asset/7eca6679-fcf1-47ab-b6e3-8c74aebb5118/mcontent.jpg
