3D BIOPRINTING TECHNIQUES - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 72

We have highlighted here several issues that must be addressed by the 3D bioprinting research com-
munity for the wide-scale adoption of this base technology for several therapeutic and nontherapeutic
applications.
Lack of digital models: Data drive the bioprinting machines. Currently there is a lack of software
architecture with necessary design tools to engineer tissue and organ systems. New data structures
must be developed to capture the heterogeneous information necessary to define such living products.
Virtually defining the placement of cells, biomaterials, and biological molecules will lead to designs
that are robust. The digital definition can also translate to drive all downstream manufacturing opera-
tions. Conventional design software revolutionized methods through which automobiles, airplanes, and
consumer and medical products are designed and manufactured. Similar software design platforms
must be available if the benefits of bioprinting are to be widely adopted by the research and industrial
communities. On a similar note, designers should also be presented with tools to simulate engineered
tissue/organoids to pursue what-if analysis scenarios. Tissue systems constantly remodel and change
over time. Tools to help predict end function, stability, and efficacy will be necessary for the wide-
spread adoption of bioprinting technologies.
Biomaterials are limited, proprietary, and expensive: Another key limitation is the limited class of
biomaterials in which the cells are encapsulated. While cell-free scaffolds are printed in a variety of
biomaterials, there has not been much development into designing newer biomaterials able to accom-
modate the encapsulated cells and the printing process in general. While it is generally understood the
cells will secrete their own extracellular matrix over time, the initial biomaterial plays an important
role in producing the right microenvironment for cells to be accommodated in their new engineered
environment. Polymers such as calcium alginate, poly-lactic-glycolic acid (PLGA), and poly-ethylene
glycol-diacrylate (PEGDA) are some of the most common polymers used in the 3D bioprinting pro-
cess. Most polymers used for bioprinting are synthesized in laboratories or are available in commercial
quantities that can be cost-prohibitive. There is a need to expand the library of biomaterials to be used
for the several bioprinting machines available. Similar to established metals and polymers with their
defined properties, new classes of printable biomaterials must be developed to produce engineered tis-
sue and organs.
Lack of adequate cell loading and uniform cell distribution: Engineered constructs of the heart or
liver will require millions of cells packed in given volume of a printed construct if they are to function
in a physiological manner. Current bioprinting techniques are limited to less than 10 M cells/ml. Im-
proving cell density to reach greater than 50 to 100 M cells/ml will be necessary for proper tissue and
organ function. Long fabrication times can lead to settling down of the cells in the printhead chamber.
This will lead to nonuniform distribution of cells resulting in inconsistent results. For bioprinting tech-
nologies that specify one or two cells per droplet, improving the reliability of cells contained within a
droplet is necessary for improving the robustness of the process.
Material development and standardization: Bio-inks are an integral part of the bioprinting technol-
ogy. It is not the bioprinting process parameters alone, but the material-process interactions that govern
the viability and success of the resultant constructs. Hence, developing appropriate bioinks and com-
prehensively characterizing their rheological, mechanical, and biological characteristics is critical to
the success of bioprinting. It is accepted that this development and characterization will have to be cell/
tissue- and process-specific. Standardization of the living as well as nonliving bioink components and
their sources is also of equal importance, not only from the final production perspective, but also during
the process development stage, since any variability in the bioink characteristics ultimately affects the