Page 245 - IJB-9-1

International Journal of Bioprinting 3D printing of smart constructs for precise medicine

gelation properties. The inkjet-based printing method Gong et al. reported that post-printing stimuli could reduce
has the advantage of producing ultra-tiny droplets that can the scaffold dimensions and generate higher-resolution
achieve single-cell deposition. However, a fine resolution is constructs . The previous studies demonstrated that
[64]
achieved using a small diameter nozzle (<100 μm), which fiber orientation in hydrogels can guide the corresponding
can easily be blocked. Therefore, to facilitate the ejection of alignment of cells through biomechanical signaling .
[65]
droplets from the nozzles, bioinks must have low viscosity Therefore, as cells form anisotropic functional tissues
(~0.1 Pa·s). Moreover, the successful fabrication of shaped (e.g., neurons and muscles), constructs can be moved by
structures using droplets of fluidic materials relies on the supplying bioelectric and biochemical stimuli.
rapid sol-gel transition of the printed inks (e.g., through In general, 3D bioprinting has a key merit that
ionic gelation and photopolymerization [57,58] ). Because of differentiates it from 3D printing, that is, living cells can
these prerequisites, inkjet-based 3D bioprinting is limited be used as building bricks. Printing flow innovations and
to depositing materials that are viscous or undergo a long- parameters are made to protect cells. However, because
term crosslinking process. However, its advantages of being of similar working principles, 3D bioprinting techniques
low cost, having high resolution, controllable droplet size, inherit the advantages of their progenitor 3D printing
uniform cell density, and a rapid deposition rate allow for the methods in building smart constructs. Undoubtedly,
fabrication of layers with patterned cellularized structures.
the recruitment of vulnerable cells shrinks the pool of
2.3.3. Microextrusion-based 3D bioprinting adaptable smart biomaterials and requires a carefully
designed fabrication process. However, the involved cells
Microextrusion-based 3D bioprinting inherits the working and generated tissues impart lives to the 3D-bioprinted
principle of FDM, which squeezes bioinks from a sharp structures, enabling accurate sensing and reacting toward
nozzle in the form of filaments (Figure 4C). In contrast stimuli comparable with the response of the human body.
to roller-driven methods for the continuous material Thus, it provides a basis for engineering smart constructs.
delivery of FDM, microextrusion-based 3D bioprinting
applies either pneumatic pressure [59,60] or mechanical Table 1 summarizes and compares the main advantages
pressure, which uses pistons and screws, to force the and limitations of each 3D bioprinting technique in terms
bioink out of the needles [61,62] . A strong extrusion force of the bioink properties, printing capacity, and cell-friendly
(up to MPa) permits this technique to print a wide range performance.
of biomaterials, including hydrogels, polymers, and cell
aggregates. Therefore, in terms of material adaptation, 3. Stimuli-responsive biomaterials toward
microextrusion-based 3D bioprinting is the most versatile precision medicine
of the available 3D bioprinting techniques. 3D bioprinting enables the precise deposition of various
The printing resolution of this technique is governed cells and biomaterials for engineering living artificial tissues
by several printing parameters: Moving speed, extrusion and organs with structural complexities. However, as the
rate, and nozzle gauge. Changing the moving speed and interest in personalized medicine increases, merely locating
extrusion rate can change the dimensions of the filaments cells and biomaterials are not sufficient in constructing
by defining the volume of bioink deposited in a certain an ideal tissue or organ. Therefore, many endeavors have
printing period. However, rapid motion or slow extrusion been implemented to develop novel biomaterials for tissue
[66]
can lead to intermittent or non-uniform filaments and engineering . Several biomaterials capable of responding
affect the printing quality. Although using a small nozzle to certain stimuli (e.g., temperature, pH, light, ultrasound,
helps refine the resolution, it may adversely affect the and magnetic fields) have been briefly introduced before
cellular activity due to the higher shear stress generated their application to 3D bioprinting (Figure 5 and Table 2).
during the extrusion process. Therefore, during the process
of cell-laden constructs, the bioink should exhibit shear- 3.1. Temperature-responsive biomaterials
thinning properties to alleviate the shear stress-induced Thermoresponsive materials respond to exogenous
damage to cells. However, strong shear stress can be applied temperature changes and undergo shape transformations .
[67]
to orient fibrous materials residing in the bioink along the The transformation principle of thermoresponsive
[63]
printing direction . The generated anisotropic alignment biomaterials is based on how their solubility and wettability
of fibers can trigger the programmed dynamic changes in change with temperature. Temperature responsiveness
hydrogels (swollen and shrunk) when printed structures enables a user-defined functionality. For example, double-
are exposed to stimuli (e.g., temperature, humidity, pH, network hydrogels were fabricated by combining two
and irradiation); consequently, smart functions, such as compositions with substantially different thermal properties
shape-morphing and locomotion, can be achieved . through crystallization [68-70] . The novel hydrogel was
[13]

Volume 9 Issue 1 (2023) 237 https://doi.org/10.18063/ijb.v9i1.638