Page 459 - IJB-9-6

International Journal of Bioprinting 3D bioprinting of in vitro cartilage tissue model

cartilage injuries still have no cure or 100% effective to be shear-thinning . Jetting-based 3D bioprinting
[11]
treatment. These diseases are extremely prevalent, enables contactless patterning and deposition of cell-laden
with rheumatoid arthritis and osteoarthritis affecting biomaterials . Although it is a manufacturing technique
[12]
0.5%–1% of the world population and 36.8% of the that highly facilitates cell–cell and cell–matrix interactions,
[1]
U.S. adult population, respectively . Due to the lack of it presents a limited choice of printable bioinks . Vat
[2]
[12]
nerve signaling and vasculature in cartilage, the latter photopolymerization-based bioprinting relies on a
is difficult to diagnose at initial stages and has a limited scanning laser that cures the photocurable bioresin in a
endogenous repair potential. Additionally, cartilage has an predefined pattern . This technique has a high fabrication
[13]
extraordinarily complex structure, presenting up to four accuracy; however, it relies on photoinitiators, which can
distinct articular cartilage zones , making it extremely be toxic when mixed with cells .
[13]
[3]
difficult to replicate in vitro. A recent systematic review concluded that of
[9]
The superficial zone comprises collagen fibers aligned the three most common cartilage 3D bioprinting
parallel to the surface and chondrocytes with an elongated techniques (extrusion-based, jetting-based, and vat
shape. Beneath this is a middle zone where collagen photopolymerization-based), extrusion-based 3D
fibers are randomized, and chondrocytes present their bioprinting was the most popular . According to most
[14]
characteristic rounded shape. Further down, the deep papers, animal-based gelatine methacrylate (GelMA) [15-23] ,
zone contains collagen fibers that are perpendicular to hyaluronic acid-based [17,22,24] , or chondroitin sulfate-based
the tide mark and rounded chondrocytes positioned materials [15,24] were used. Although alginate is also one of
in columns in the same perpendicular orientation. The the most commonly used materials in bioprinting, its poor
deepest calcified cartilage zone contacts with bone and cell attachment properties require that it be mixed with
contains hypertrophic chondrocytes . In addition to other GelMA, hyaluronic acid-based, and chondroitin
[3]
this complicated structure, the lack of vasculature forces sulfate-based materials to enhance these properties.
nutrients to be distributed through diffusion , making Even though these mixed materials are widely used, they
[4]
tissue healing not only challenging but also a slow process. present multiple disadvantages such as low reproducibility,
Due to these difficulties in natural regeneration, multiple scalability, and low mechanical property [25,26] . Furthermore,
studies have focused on recreating cartilage in vitro to there is a need to move toward a more sustainable and
use it as implants in vivo [5,6] or to study potential tissue ethical approach in science, encouraged by the EU
regeneration methods [7,8] . Directive 2010/63 and the Guidance Document on
Good In Vitro Method Practices , hence prompting the
[27]
Current tissue engineering techniques have been used
in attempt to develop in vitro cartilage constructs using exploration of non-animal-derived synthetic materials as
a viable alternative.
natural or synthetic polymer-based scaffolds that are
then populated using two-dimensional (2D) cell seeding Synthetic polymers can be modified to improve
approaches. Depending on the porosity of the material, their mechanical and physical properties as well as to
cells exhibit different colonization rates and viabilities. control their degradation time; these advantages also
However, this approach has a lack of control over three- result in better reproducibility and less batch-to-batch
dimensional (3D) cell colonization and a lack of structural variation. Prior studies have demonstrated the potential
control over the scaffold itself. 3D bioprinting, a technique of synthetic self-assembling peptide hydrogels for use in
that enables layer-by-layer manufacture, has been used to cartilage studies [28-30] . Such transparent peptide materials
overcome these limitations . 3D bioprinting allows for are shear thinning and do not require crosslinking,
[9]
multi-structural and controlled manufacturing as well as making them perfect off-the-shelf materials for easy and
homogeneous deposition of encapsulated cells within the accessible bioprinting. Due to their synthetic nature, there
bioprinted structure . Intricate 3D CAD (computer- is a minimal batch-to-batch variation, which ensures
[10]
aided design) designs can be made to recreate the different reproducibility in printed structures, making them an
cartilage layers and better mimic the characteristics of exceptional alternative to natural materials. Preliminary
this tissue. Multiple 3D printing techniques are currently studies have also shown the potential application of these
used, such as extrusion-based, jetting-based, and vat self-assembling peptides in 3D bioprinting . Due to the
[31]
photopolymerization-based. Extrusion-based technique differences between hydrogel performances (synthetic or
combines a fluid-dispensing system and a robotic natural), it is not currently possible to define a hydrogel-
control system . It presents advantages such as a great based “gold standard” system for cartilage manufacturing
[11]
deposition and printing speed, affordability and a wide in vitro. Therefore, when assessing the performance of a
range of potential printing materials . However, its hydrogel for cartilage in vitro manufacturing, comparing
[11]
resolution is limited, and most materials printed require it to the native tissue is preferred. Alternatively, in vitro

Volume 9 Issue 6 (2023) 451 https://doi.org/10.36922/ijb.0899