3D BIOPRINTING TECHNIQUES - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 56

CHAPTER

3

3D BIOPRINTING
TECHNIQUES

Binil Starly and Rohan Shirwaiker
Department of Industrial and Systems Engineering, North Carolina State University, Raleigh, NC, USA

3.1 INTRODUCTION
Critical to the success of tissue engineering and regenerative medicine (TERM) approaches, which require
the use of a structural matrix, is the design of the scaffold and ensuing tissue construct. Cells involved in
the regeneration process are influenced by the macro- and microarchitecture of the constructs. Two pri-
mary approaches have been developed to produce scaffolds and tissue constructs: (1) chemically driven
processes, such as gas foaming, solvent casting, salt leaching, and freeze casting; and (2) computer-
aided layered manufacturing- based approaches. Scaffolds produced through either of these approaches
create structural matrices with defined pore architecture in terms of size, shape, and orientation. The
three-dimensional (3D) surface area offered by these scaffolds serves as anchoring surfaces for cell
adhesion, proliferation, and differentiation to the desired tissue type and function. In these approaches,
scaffolds are produced first and the cells of interest are added in a subsequent processing step. The
main drawbacks of this approach are the lack of cellular penetration and highly variable cell distribu-
tion within the scaffold matrix, primarily seen in scaffold sizes larger than 5 mm in thickness. These
limitations arise from two reasons: (1) low cell seeding efficiency at the initial stages to fully inoculate
the scaffold itself; and (2) lack of cellular proliferation deep into the scaffold architecture primarily
due to rapid drop-off of nutrient concentration within the scaffold core. Several approaches have been
developed by the research community over the last decade to mitigate these disadvantages. One popular
approach has been the adoption of perfusion-based bioreactor systems to help improve cell seeding ef-
ficiency and the transport of nutrients within the scaffold to promote more uniform cellular adhesion
and proliferation. An added benefit is that these bioreactors can be customized to provide mechanical
and chemical stimulation to accelerate tissue formation. While generally successful, these methods are
often limited to small- size defects and thus cannot be translated to thicker tissue constructs.
A more exciting approach is to directly involve cells within the construct design and fabrication
process. This offers the advantage of combining multiple processing steps together through which a
cellular construct is directly achieved. This approach helps to overcome the seeding efficiency and
cell distribution problem. It opens up newer opportunities to customize and regulate the cellular mi-
croenvironment by the controlled placement of cells and other biological molecules in defined spatial
orientation. In recent years, this approach has rapidly taken off, with several fabrication processes being
developed to build in situ cellular constructs. These processes include photopolymerization-based pro-
cesses, laser-based patterning, contact stamping, and cellular microencapsulation to form multicellular