Medical Materials As early as 1988, Robert J. Klebe from University of Texas
Health Sciences Center presented a vision of the bioprinting process in his publication, Cytoscribing: A Method for Mi- cropositioning Cells and the Construction of Two- and Tree- Dimensional Synthetic Tissues. Since then, hundreds of studies have been conducted including successful printing of bones, menisci, vasculature, heart valves, and ears as well as biore- sorbable tracheal splints. Many experimental 3D bioprinters have been developed, and some have become commercialized, including the high-end Envisiontec Bioplotter as well as the lower-cost Seraph Robotics’ Bioprinter, which was developed at Cornell University. Most of these machines allow automat- ed, rapid, scalable, and personalized printing as they utilize living cells. Tey also achieve uniformity while reducing print- ing time, costs, and expertise needed for tissue engineering. Te Envisiontec Bioplotter is able to print with a wide range of materials, including hydroxypapatite, titanium, and tricalcium phosphate (TCP) for bone regeneration; polycaprolactone (PCL), polylactic-co-glycolic acid (PLGA), and poly-l-lactide (PLLA) for drug delivery; agar, alginate, collagen, chitosan, fibrin, and gelatin for soſt tissue biofabrication and organ printing; and polyurethane and silicone for concept modeling. Te bioprinting process is currently realized through two
different techniques: biological laser printing—the technol- ogy used in the Envisiontec bioplotter—and biological ink-jet printing—the basis of the Seraph Robotics Bioprinter.
Biological Laser Printing Biological laser printing (BioLP) is an automated CAD
based transfer process where a laser beam moves cells covered by a medium, usually within microbeads or microcapsules, onto the receiving substrate. It is capable of rapidly depositing living cells onto a variety of surfaces. Unlike other techniques such as ink-jetting printing, the process delivers a small vol-
ume of a variety of biomaterials without using an orifice, and eliminates potential clogging issues and damage to the cells. Today’s laser-assisted bioprinting technology applications include laser-based micro patterning of cells in gelatin, cell assembly, bioprinting of skin, and laser-engineered microenvi- ronments for cell culture. Aſter intensive efforts in late 1990s for using biological
media in sensor development and coupling it with lasers in fabrication, BioLP was developed in 2004 by a group of researchers from the Naval Research Laboratory and the He- brew University of Jerusalem. Tey used a laser-based printing method to deposit bacteria, with the ability to respond to various chemical stressors, onto agar-coated surfaces and into microtiter plates. Initial work yielded smaller printing spots, increased resolution, and better repeatability compared to other related techniques. Deposition rates up to 100 pixels of biological material per second were achieved. Te original cell printing experiments not only demonstrated close to 100% vi- ability, they also were the first steps toward using BioLP to cre- ate heterogeneous 3D tissue constructs. More recently, in 2012 Vienna University of Technology (VUT) researchers devel- oped a new variant, called 3D Photograſting, to grow biologi- cal tissue or to fabricate microsensors by using two-photon lithography. Te VUT scientists start with a hydrogel scaffold which is made from macromolecules arranged in a loose meshwork. Te 3D Photograſting method is then used to introduce selected biomolecules into the hydrogel meshwork where the laser beam is focused by breaking photochemically labile bonding. Te laser produces intermediates which are very reactive and consequently attached to the hydrogel very quickly. Based on the laser’s lens system, resolutions as fine as 4 µm can be obtained. Laser-assisted bioprinting process has proven to be suitable for depositing multiple cell-types adjacently, producing larger-
Two views of a Cornell University bioprinter printing cartilage cells encapsulated in collagen hydrogel to help develop a new earlobe.
52 Medical Manufacturing 2014
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