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Liang, et al.

B C

A

Figure 2. (A-C) A basic summary of 3D-bioprinting repair of cartilage tissue.

speed ratios from 0.07 to 2.24 mm by the Integrated Tissue- functional groups in the bioink polymers . Compared
[17]
2
Organ Printer system. In addition, both storage modulus with the natural sources which are usually crosslinked
and loss modulus increase as the cell density increase, with physically, the methacrylate functionalized polymers
no change in the shear viscosity observed . Nevertheless, are photocrosslinked covalently, thereby improving
[12]
encapsulated human glioblastoma cells have been the mechanical strength of the hydrogel. Moreover,
demonstrated to impair the printing resolution of gelatin nanomaterials, including graphene, nanoclay, and
bioinks using extrusion 3D bioprinting . Furthermore, ceramics nanoparticles, are also applied to reinforce
[14]
higher cell densities may enhance the steady shear viscosity hydrogel-based bioinks . In addition, additives to
[18]
while reducing the threshold of extrusion pressure, which improve the printing resolution of printouts are also used.
contributes to the bioink compressibility and the friction For example, the click reaction between thiols and alkene
between cells and the hydrogel during the printing process. groups added to the bioink polymers can solidify the
Common bioinks additives include (i) additives material immediately during 3D printing, thereby enabling
that improve biocompatibility and repair efficacy; the fabrication of complex yet high-quality constructs .
[19]
(ii) additives that enhance hydrogel crosslinking and Furthermore, photoabsorbers, such as tartrazine, are also
mechanical properties; and (iii) additives that refine popular additives for the crosslinking and resolution
printing resolutions. Growth factors are important improvement of photocrosslinkable hydrogels .
[20]
additives of bioinks. They are important for inducing Different bioinks correspond to different 3D printing
cellular response, thereby stimulating cell differentiation techniques. One of the most commonly used technology is
and tissue regeneration. In addition, they are essential in extrusion-based printing (EBP) (Table 4), which requires
enhancing chondrogenesis and inhibiting chondrocyte the bioink to be loaded into plastic or stainless steel
hypertrophy . Basically, the most widely applied cartridges and then extruded through a printing nozzle
[15]
growth factors include transforming growth factor-β onto a platform (Figure 3A). It supports 3D printing
(TGF-β) (Table 4) which promotes cell proliferation with cell-laden bioink and its printouts are of moderate
and chondrogenesis; bone morphogenetic proteins resolution [7,21] . Moreover, as mechanical extrusion printing
that improve the production of ECM; insulin-like allows both bioink deposition and withdrawal, it enables
growth factors which promote the differentiation of a clean cut of the bioink strand and the correction of
mesenchymal stem cells, fibroblast growth factors that printing errors, thereby achieving an improved shape
maintain ECM homeostasis, and platelet-derived growth fidelity of the printouts . Nevertheless, the viscosity of
[22]
factors which enhance the formation of heterotopic the bioinks applied must be high enough to avoid shape
cartilage . In addition to the growth factors, additives collapse . As for cell-encapsulated bioinks, shear-
[16]
[23]
are also used for the crosslinking of hydrogels and thinning characteristics are required for the hydrogels to
the enhancement of mechanical properties in bioink prevent cells from damage caused by shear stress when
development. Methacrylate anhydride is one of the existing the nozzle . Gelation methods, including
[21]
most popular chemicals for generating methacrylate temperature/pH change and photocrosslinking, can be
International Journal of Bioprinting (2022)–Volume 8, Issue 3 17