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International Journal of Bioprinting Bioprinting cell-laden protein-based hydrogel
specific tissue (cartilage or bone), and different signaling of encapsulated cells into a desired structure. Although
pathways which occur within the cells (autocrine, many PBHs, such as collagen and fibrin, exhibit the above-
intracrine, endocrine, paracrine, and juxtacrine signaling) mentioned qualities, they cannot be readily tailored, and
or those received from other cells. In the fields of cartilage there are several challenges in their printing [163] . Bioprinting
and bone TE, several research projects have been conducted strategies and bioink properties are directly influenced by
so far to assess the impacts of mentioned environmental chemical, physical, and biological characteristics; in this
cues on the cellular features and tissue development ability regard, Figure 4 presents key considerations required for
of the PBHs. The original experiments mentioned above, bioprinting cell-laden PBHs.
alongside the achieved outcomes, will hopefully provide a
comprehensive roadmap to move these fields forward. 4.1. Mechano-rheological considerations
To be an optimal bioink for various bioprinting modalities,
4. Process compatibility considerations of a material must possess several essential characteristics; for
PBHs instance, a major factor affecting biomaterial printability
is its mechanical properties. In multiple cases, scholars
Bioprinting requires the proper design of a bioink to perform long-term incubation of cell-laden constructs for
support tissue growth, cellular viability, and printability [160] , tissue development, and an integral part of this procedure
and an efficient transfer of nutrients and oxygen within the is guaranteeing structural integrity. Notably, a printed
bioink must be ensured by the PBH’s structure [161] . construct should provide oxygen and nutrient transport
into the cells, a critical subject to consider when designing
Biocompatibility and mechano-rheological features [164]
are primarily responsible for bioink printability. its architecture .
Biocompatibility is essential in developing bioinks to Inkjet and extrusion-based bioprinting techniques are
prevent adverse effects on the viability, proliferation, based on viscoelasticity and rheological characterization.
or differentiation of cells encapsulated within [162] . PBHs and the amino acid sequences of fibrous proteins,
Moreover, a bioink with appropriate mechano-rheological including collagen, elastin, silk fibroin, keratin, resilin,
characteristics can be extruded easily, maintain its shape and fibrin, play both mechanical and architectural roles
after printing, and support the deposition and organization in nature, which make them attractive choices for these
Tables 3. Recapitulation of biochemical parameters affecting PBHs’ bioprinting in the cartilage and bone TE
Considered Bioink composition Cell type (cell density)/ Printing method/ Results Reference
factors animal model/target crosslinking
tissue approach
Gelatin (1.5% w/v)/ Primary chondrocytes Extrusion/physical • Enhanced cellular viability, [136]
silk fibroin (7% (10 cells/mL)/-/ crosslinking improved cell adhesion, and
6
w/v) cartilage increased ECM formation com-
pared to controlled group
• Improved printability due to the
shear-thinning behavior of silk
and the high viscosity of gelatin
Sodium alginate Mouse MC3T3-E1 Extrusion/physi- • Promoted cellular proliferation [137]
dialdehyde (7.5% preosteoblasts (5 × 10 cal and chemical during 28 days of cultivation
6
w/v)/ gelatin (15% cells/mL)/-/bone crosslinking (ionic
w/v) with FS and enzymatic
particles crosslinking,
respectively)
GelMA (10% w/v) hBMSCs (1 × 10 Extrusion/chem- • Observed sparse distribution of [138]
7
Chemical structure gelatin (80 mg of (photo-crosslink- • in GelMA structures
cells with spherical morphology
ical crosslinking
cells/mL)/-/cartilage
and silk fibroin/
gelatin powder
ing and enzymatic
Homogenous distribution of cells
with some of them exhibiting a
crosslinking)
in 800 µL of silk
spread morphology on day 21 in
fibroin solution)
silk fibroin/gelatin constructs
Volume 9 Issue 6 (2023) 480 https://doi.org/10.36922/ijb.1089

