scale cell arrays and multilayer cell constructs. Recent work in the field includes biofabrication using laser in patterning stem cells, microbeads, and cell-loaded microcapsules at Rensselaer Polytechnic Institute (Troy, NY); in-situ and in-vivo bioprinting
Tissue scaffolds are used in tissue engineering to provide a temporary 3D structure on which cells can be manually or automatically attached (through 3D printing) and then grow and create new tissue. Tissue scaffolds are not easily con-
Bioprinting is at the intersection of tissue engineering, regenerative medicine,and 3D printing.
of cells and biomaterials at the University of Bordeaux (Bor- deaux, France); and skin tissue generation by laser cell printing at the Laser Zentrum Hannover E.V. (Hannover, Germany).
Biological Ink-jet Printing For many years, ink-jet technology has been used as a help-
ful tool in providing a noncontact technique to print inks in a rapid manner. Recently, this technology has been applied in the medical field by using encapsulated cells as the ink (bio-ink) in order to print tissues and organs, including heterogeneous tissue and microvascular cell assembly as well as biomaterials. With help from a pressurized air-supply controlled by solenoid valves, these bioprinters deposit encapsulated cells onto the substrate to generate 3D constructs such as an earlobe. According to Tomas Boland of the University of Texas at
El Paso, bio ink-jet printing can produce 100 million drops per second. Tat makes this method very rapid as well as con- venient since the printer can be transported with ease and can use many different types of ink. Te drops that are produced by the printer are very small; usually in range of 20–60 µm. When using different types of ink, it is important to determine the printability of the material. Te printability can be deter- mined by using the surface tension, density, viscosity, and the critical dimension of the printing material. Tere are many types of inks that can be used with biologi-
cal ink-jet printing, including alginate, chitosan, and collagen as well as reactive inks such as cross-linkers and proteins, and polypeptides. When printing and manipulating live cells, it is important to be aware of the apoptosis—the natural death rate of the cells. According to Boland, when cells are printed the apoptosis rate is 3.5 ± 1.3% while cells that are pipetted have a rate of 3.2 ± 1.6%. Tus, the inkjet printing of cells does not have any significant effect on the death rate of the cells, opening doors to endless opportunities and advantages in the medical field. Recent work with this method included printing of cartilage-based constructs including artificial ears at Cornell University (Ithaca, NY) and Princeton (Princeton, NJ) as well as other tissue and organ constructs at Wake Forest Institute for Regenerative Medicine (Winston-Salem, NC).
Handling Scaffolds for Tissue Growth Wei Su from Drexel University (Philadelphia) recently pre- sented his findings on fabricating scaffolds for tissue growth.
structed; there are many challenges. For example, the biomate- rials being used must be carefully considered to see if they are biocompatible, biodegradable, or bioresorbable. Creating the right porosity and pore size of the scaffold is also a challenge. A large surface area gives the cell a place to attach and grow while a large pore volume adequately houses the cell. A high porosity is important because it makes it easier for the diffu- sion of nutrients and vascularization. Once these challenges are overcome, a complete set of
design constraints for the scaffold needs to be considered. Bio- physical constraints deal with the scaffold’s structural integrity, strength, stability, and degradation, as well as the cell’s specific size, shape, porosity, and inter-architecture. Biological require- ments deal with where the cell will attach, grow, and how the new tissue forms. Some other constraints include how the scaffold will perform anatomically and the manufacturability of the scaffold. Aſter all of the challenges and constraints of the tissue scaffolds are handled, these scaffolds can be used to create 3D prints of organs, blood vessels, and even to create 3D models for drug release mechanisms.
The Future Today’s successes in printing tissue for skin, heart valves,
or earlobes can be complemented by successful printing and implantation of complex tissue assemblies with multi-material presence as well as complete bioficial organs such as a heart or a kidney in the future. However, successful bioficial organ printing relies on future developments in hardware and associated processes as well as successful printing of blood vessels and, especially, tissue with embedded vasculature. Re- cent research is showing promise in getting complex printed tissue to attach itself to the vascular network of an existing environment aſter implantation. Current studies are focusing on advancing printable cellular microfluidic channels, living lithography, fabrication of cellular materials with embedded vascular networks, printable Human Umbilical Vein Endo- thelial Cells (HUVEC) networks and direct printing of blood vessels. Hydrogel biopapers and BiOLP are showing promise in fabricating tissue with embedded vasculature. Additional attempts are also being made in bone and skin repair by directly printing on the existing tissue and in-vitro diagnostics for understanding the dynamics of the biochemistry of the organs and tissues.
Medical Manufacturing 2014 53
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