Page 87 - IJB-9-1

International Journal of Bioprinting Progress in bioprinting of bone

the final construct, this process is repeated several times in
a layer-by-layer manner [16,17] .
Aspiration-assisted bioprinting (AAB), which has
recently been developed to manipulate cell spheroids, is
a new bioprinting technique that capitalizes on the fact
that spheroids can be formed from diverse cell types at
high densities, lifted by employing negative air pressure,
and bioprinted on a hydrogel (Figure 2D). The above-
[18]
mentioned bioprinting processes are sometimes integrated
to obtain optimal mechanical and biological properties.
2.2. Selection of bioink
Different cellular responses have been observed when
Figure 1. Design flow for bioprinting a bone construct. natural hydrogels are used for bone bioprinting. For bone
bioprinting, alginate has always proven to be a popular
(iv) Besides the well-acknowledged growth factors, are biomaterial due to its biocompatibility, low cost, and ease
there other biologicsor supplements that can be of cross-linking by contact with calcium (Ca ) ions .
[19]
2+
incorporated in bioprinting and are they conducive to The low bioactivity of alginate poses a limitation to its
osteogenesis? use. As compared, the similarities between collagen and
(v) What can be carried out to compensate for the weak native bone make it an ideal material for bone bioprinting.
mechanical properties of bioprinted bone resulting It is, however, difficult to generate collagen hydrogels
from the nature of cell-laden bioinks? with high viscosity that have rapid gelation capabilities.
(vi) As bone cells are highly metabolically active, how Therefore, collagen was only used in a handful of bone
does the hypoxic culture environment impact the bioprinting studies, usually in combination with other
maturation of bioprinted bone? biomaterials. Since gelatin is derived from collagen, it
(vii) How do bone cells respond to mechanical stresses in is a more economical option and is used in conjunction
the bioprinted constructs in terms of cell morphology, with other biomaterials to form bioinks. The biological
osteogenesis, and mineralization? functions of bioprinted bone can also be regulated by

2.1. Bioprinting apparatus other popular biomaterials, such as agarose, chitosan,
and hyaluronic acid (HA) [20,21] . Aside from mixing several
The common bioprinting processes, including extrusion- natural polymers with varying concentrations to tailor
based bioprinting (EBB), droplet-based bioprinting (DBB), bioink properties, polymers can also be modified to
and laser-based bioprinting (LBB), have been utilized have customized properties. For example, methacrylate
for bone bioprinting, depending on the selective bioink hydrogels, which are natural components of the ECM
formula. In EBB, the bioink is deposited from a syringe or modified by methacrylation, are widely used in the field
nozzle onto a build platform based on a computer-aided of bioprinting . As one of those hydrogels, gelatin
[22]
design of the structure to be printed (Figure 2A). This is methacrylate (GelMA) is becoming a popular biomaterial
accomplished by laying down small cylindrical deposits for 3D bioprinting [23,24] , due to its biocompatibility as well
of the material, either pneumatically, mechanically, or as its ability to cross-link chemically with UV light under
by solenoid-driven deposition. In general, bioprinted physiological conditions . Another example of hydrogel
[25]
bone constructs are primarily fabricated by EBB due to is methacrylated HA (MeHA) , which has been combined
[26]
its efficiency in printing large-scale constructs in 3D, and with GelMA hydrogel for bone bioprinting .
[27]
its flexibility to handle a variety of biomaterials to obtain
sufficient mechanical strength. Meanwhile, in DBB, bioink These above-mentioned polymers can directly
with modulated fluid properties (e.g., surface tension bioprint with cells; however, the application of cell-laden
and viscosity) is manipulated to form droplets and then hydrogels in hard tissue regeneration has been restricted
constructed using gravity, atmospheric pressure, and fluid by their low mechanical properties [28,29] . Consequently,
mechanics (Figure 2B). The LBB process involves the use biomaterials such as ceramics, thermoplastics, or alloys
[15]
of a laser pulse directed through a mirror onto a layer of that were traditionally used for the manufacture of bone
bioink. In LBB processes based on photopolymerization, scaffolds could be incorporated with hydrogels to boost
an ultraviolet (UV) laser is used to cure hydrogels in a vat the mechanical strength of the bioprinted bone [28,30-32] .
that is capable of photocrosslinking (Figure 2C). To build There are multiple options for biomaterials that imitate the

Volume 9 Issue 1 (2023) 79 https://doi.org/10.18063/ijb.v9i1.628