3-D Bioprinting By: Kareem Boura

What is 3-D Bioprinting Process in which cell patterns are created using 3D printing technology. These layers of living cell create tissue resembling structures used in medical and engineering fields. Bioprinting has shown to have precision on the spatial placement of cells, proteins, DNA, drug particles, growth factors and biologically active particles to guide tissue generation and formation better. Most Bioprinters during printing a produce a dissolvable gel output onto the tissue to protect cells during printing Cell function and viability are preserved within the printed construct

What is Bioink Bioinks are cell suspensions in hydrogels housed in printing cartridges. There basic function is tissue regeneration, generally on superficial surfaces

Applications of 3-D Bioprinting Bioprinting applications include but are not limited to: Printing tissue for transplants Using printed tissue to research effects of drugs and pills (drug screening) Printed scaffolding to be used for the regeneration of joints and ligaments Bioprinting for cancer research

History January 1998: A team of Canadian researchers create artificial blood vessels by wrapping sheets of cultured human cells into tubes. No printing involved but was a large step for this innovation. October 1999: Researchers at the university of Minnesota and Michigan technological university demonstrate that lasers can direct the deposition of cells in two dimensions. April 2003: Thomas Boland modifies an ink-jet printer to use biological materials such as proteins and bacteria. March 2004: Gabor Forgacs and his team develop multicellular spheroids for 3-D bioprinting. These orbs fuse to resemble tissue. 2006 First patent for an ink-jet printing of biomaterials. September 2009: Organovo and Invetech create the first commercial bioprinter the NovoGen MMX September 2010: Skin is bioprinted directly onto mice to help heal burns May 2013: Princeton university researchers bioprint a working ear December 2013: Cornell University researchers bioprint an artificial heart valve November 2014: Organovo 3-D prints liver tissue for drug screening

Multicellular Spheroids

Inkjet Bioprinting Replace Ink with Bioink (Bioink: cells and biomaterials) Two different types of inkjet printers, thermal or piezoelectric Thermal Inkjet printers use an ink chamber with a small number of nozzles and heating element, to generate the ink droplet a short current pulse is applied to the heat element. As the heat increases a bubble is formed that forces the ink out of the nozzle. The use of heat in this printer affects cell viability. Piezoelectric inkjet printers use piezocrystals which are located at the back of the ink chamber, after an electrical charge is applied to the crystals, they vibrate. Inward vibration forces ink out of the nozzle. Specific vibration frequencies may disrupt cell membranes and cause cell death.

Limitations Of Inkjet Bioprinting Low upper limit for viscosity of bioink Material Throughput Reproducibility of droplets Cell aggregation and sedimentation in the cartridge reservoir Clogging of the Nozzle

Laser Powered Bioprinting Laser energy is used to excite cells and give patterns to control the cellular environment spatially. A laser pulse guides each individual cell from a source to a substrate. This pulse is used to transfer the cells in a solution from a donor slide to a collector slide. The pulse creates a bubble which consequently creates a shockwave eventually forcing cells to transfer to the collector substrate.

Laser powered Bioink The absorbing layer helps keep laser pulses from killing cells

Limitations of Laser Bioprinting Heat generated from laser energy/light may cause damage to cells or affect the cells ability to communicate and aggregate in the final tissue construct. Cell viability in laser bioprinting is lower of that in inkjet based bioprinting. Printing with precision in third dimension after the gravitational and random setting of cells

Extrusion-Based Bioprinting Combination of mechanical fluid dispensing system and an automated robotic system for extrusion and writing. Mechanical fluid dispensing systems include piston-driven and screw-driven Piston-Driven: allows for more direct control over the flow of bioink through the nozzle. Screw-Driven: allow for more spatial control and are beneficial for dispensing bioinks with higher viscosities Mechanical systems are advantageous due to the various types and viscosities of bioinks that can be used by adjusting the pressure and valve gating time. During bioprinting, bioink is dispensed by the deposited system and then crosslinked by light, chemical or thermal transitions resulting in the precise deposit of cells encapsulated in cylindrical filaments of the desired shape. Most convenient technique for producing 3-D porous cell structures.

Limitations of Extrusion Based Bioprinting Screw-driven extrusion can generate large pressure drops along the nozzle which can potentially harm loaded cells. Stress and limited material selection due to the need for rapid encapsulation of cells Using a higher pressure inks with high viscosity could be used but the increase in pressure may reduce cell viability. Changes in pressure, nozzle geometry and bioink concentration can kill cells.

Future 3-D Bioprinting is hoped to be used for replacement organs when the science matures to that stage. Eliminate animal drug screening through the use of printed cell tissue. Through the use of nanotechnology and genetic engineering bioprinting may also prove to be an important tool for life extension. Printing cells directly onto the human body in order to rapidly heal the affected surface.

References Dababneh, Amer B., and Ibrahim T. Ozbolat. "Bioprinting Technology: A Current State-of-the-Art Review." Journal of Manufacturing Science and Engineering. ASME, 24 Oct. 2014. Web. 16 Oct. 2016. <http://manufacturingscience.asmedigitalcollection.asme.org/article.aspx?a rticleid=1903284 > Davenport, Matt. "Print Your Heart Out." CEN RSS. N.p., 9 Mar. 2015. Web. 16 Oct. 2016. <http://cen.acs.org/articles/93/i10/Print-Heart.html> "ExplainingTheFuture.com : Bioprinting." ExplainingTheFuture.com : Bioprinting. N.p., n.d. Web. 16 Oct. 2016. <http://www.explainingthefuture.com/bioprinting.html>