Biocompatible Inkjet Printing Technique for Designed Seeding of Individual Living Cells
http://www.liebertonline.com/doi/pdfplus/10.1089/ten.2005.11.1658
MAKOTO NAKAMURA, M.D., Ph.D.,1 AKIKO KOBAYASHI, M.D.,
FUMIO TAKAGI, M.S., AKIHIKO WATANABE, Ph.D., YUKO HIRUMA, D.D.S., Ph.D.,
KATSUHIRO OHUCHI, M.S., YASUHIKO IWASAKI, Ph.D.,
MIKIO HORIE, Dr.Eng., IKUO MORITA, Ph.D., SETSUO TAKATANI, Dr.Eng.
Organ transplantation is the current solution to end-stage organ failures. However, the availability of suitable donors is severely limited and many patients cannot afford to wait too long for an organ transplant. While making tissue-engineered organs using biological materials is a promising solution to the shortage of organ donors, it is very difficult to recapitulate the precise spatial arrangements of different cell types and extracellular components of an actual organ. This paper investigated the feasibility of a novel TE technique called “bioprinting”. Inspired by inkjet printing technology in commercial printers, this technique can potentially allow for high-resolution seeding of living cells in an arrangement similar to biological tissues.
First, a cell printing system was constructed using an electrostatically driven inkjet head made of glass and silicon. This inkjet head is biocompatible and does not generate too much heat, which is important in keeping the cells alive as they are being ejected. Bovine endothelial cell suspensions were then used as the “ink” and printed onto PET culture disks as one-dot-thick lines. After printing, the culture disks were incubated and checked later for cell viability.
Comparing with floating and adhered endothelial cells, the authors found that the dots were printed at nearly the same size and resolution. Phase-contrast microscopy indicated that the 0-4 cells were situated inside the printing dots, depending on the concentration of the original cell suspension. Time-lapse recordings showed some of the cells could adhere onto the culture disks for proliferation, a strong indication that the cells were still alive. Finally, SEM images showed no changes in cell morphology before and after printing, indicating that no significant mechanical damages were inflicted on the cells during ink ejection.
The results led the authors to believe that inkjet printing of living cells is a feasible method for making TE organs. Besides the ability to precisely arrange cells in high resolution, there are also other potential advantages in this inkjet system. For example, the concept of color printing can easily be applied. By using growth factors, polymers, ECMs etc as “color ink”, we can simultaneously position these essential components along with the living cells. Also, inkjet printing can be operated at high speed, thus reducing the time to make an organ. The printer can also transmit digital data to a computer, allowing bioengineers to design organs virtually to fit clinical and individual needs.
There are a few issues to consider in future developments of this technique. Since living cells and other biological molecules are used, the inkjet system must be biocompatible. Heat generation during the printing process must also be minimized because most biological materials are heat-sensitive. The authors believe an electrostatically driven system used in their experiments is the most suitable for this purpose. In conclusion, biocompatible inkjet printing seems to be a great alternative to organ transplantation, even though many essential improvements such as “color printing” discussed above still need to be developed.
11 comments:
Did the authors try designing 3D tissue constructs, or did they only test out adherent 2D tissue cultures for this experiment? If they were able to print three dimensional constructs with more than one cell type, then this definitely would be a way to get around the problems with organ transplants. It might even be possible to use the patient's own cells in the printing and thus limit any potential immunorejection problems.
I believe the authors only printed single lines of cells to test if this method would actually work; so yes they were 2D.
You are definitely right that a 3D tissue construct is what scientists ultimately want to achieve. Theoretically, one can print various types of cell onto a gel or other solid materials, and print layers of them to form a three dimensional structure. If this can be done, it would be much better than pouring cell suspensions in bulk onto a scaffold because the precise locations of cells can be controlled.
Are there particular types of cells that you can print? Or does this apply to all kinds of cells?
This technique sounds really cool! I agree that this would definitely be a great solution to the unavailability of organs for transplantations. Seems like the technique is very precise - but what if, hypothetically speaking, an extracellular component was incorrectly arranged during the process? Is there a way to fix the error while printing, or would researchers have to just start over on a new culture disk?
David,
I would think this method can be applied to many if not all cell types, as long as they can withstand some amount of heat and mechanical stresses during the printing process (which are the main concerns for many people).
Actually there's quite a number of papers out there that have tested this method. I looked up on Google Scholar, and apparently people have successfully printed stem cells, embryonic motoneurons, Chinese Hamster Ovary (?!), among others. So I think this is a good indication that inkjet printing is widely applicable.
Elena,
That's an interesting question...but the author didn't mention any error-fixing mechanism. Just an imagination....maybe and hopefully there're some enzyme or reagents that can degrade & solubilize the unwanted stuff, then wash it out and do a reprint. And reprint should be possible because this method is supposedly very precise.
To be honest, when I read about this, I just thought: "WHAT THE..." So, I was impressed. This is really cool stuff. Cell specifically located by a printer...factors added with color printing feature...really nice. However, you mentioned the "biocompatible" word a few times. What standards are this guys using to meadure biocompatibility on a printer? What do you undesrtand by biocompatible? Is it anything cell-like, anythig that does not kill the cell (e.g. temperature), or is it anythig that doesn't starts an immune response?
This idea is so smart. But how come we can't just seed the cells ourself? Do they use this technique because it's more convenient?
V,
Biocompatibility is discussed qualitatively in this paper. Temperature is part of the consideration, and so as the materials that are used to build the printhead. So for instance a thermally driven ink ejection mechanism would be bad as the temp can go up to 300C. Silicon and glass are preferred materials for the printer as they are stable with heat and chemicals, which is good for keeping things sterile.
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manyeung,
yeah, definitely for convenience and much better precision. I can't imagine making a liver with my P10 pipette (not to mention changing the pipette tips, which tend get STUCK in those racks, or at least mine is...) Anyway, I should also mention that the printer can print cell "dots" within a 20 micron interval, not bad for a commercial printer.
I think that it’s quite neat that people are using current technologies and applying it to new things! yay for engineering. You stated that this printing method is good for use of tissue construction for those that need them. It would seem to me that given that vast number of cell in an organ, I'm wondering if there has been any data compared to the time lengths needed to generate these transplants and how big of a transplant the technique can manage. While you suggest that tissues be assembled, is it really feasible to create tissue mimics that can be functional in a limited time scale set by the patient? What kind of tissues can be made, (ie. are there any special and specific ones? :D)
This method is great: there is a greater need to analyze single cells than a bulk of cells together to examine the behaviors of a single cell. This method would be able to address this.
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