Page 21 - IJB-9-2

International Journal of Bioprinting Extrusion-based biomaterial inks

in methyl ethyl ketone and successfully printed in a grid level [165,166] . Besides, the activity of cells embedded in it
structure with a printing temperature of 20°C [118] , thereby is low and can only be maintained at about 70% due to
preventing high-temperature damage to the cells. Another the problem of mechanical force [167] . Therefore, similar
low temperature printing strategy of thermoplastic to nanoclay, nanocellulose not suitable to be used as cell
polymers is blending printable hydrogels with polymers embedding biomaterial ink.
in the form of microspheres. The mechanical strength of Hydroxyethyl cellulose and methylcellulose are both
printed constructs is greatly improved and up to more than water-soluble non-ionic cellulose derivatives. They have
100 times after adding PLGA porous microspheres into been used in extrusion-based bioprinting to adjust the
agrose–collagen hydrogel . viscoelasticity of inks for improving the printability due
[80]
3.3. Rheological additives to their shear thinning performance. For example, the
Rheological additives are rheological control agents for shape fidelity of printed filament is improved by adding
[96]
coatings in the industrial field. The main function of methylcellose into alginate . Law et al. used blends
rheological additives is to improve the viscosity of coatings, of hyaluronic acid and methylcellose with different
and then improve the anti-settlement during storage and concentrations as biomaterial ink for bioprinting
anti-sagging during construction. Rheological additives mesenchymal stem cells, and the cell viability was above
[47]
are added to biomaterial inks to improve their rheological 75% in bioprinted structures . Hydroxyethyl cellulose
properties and printability so as to ensure the fidelity of is an environmentally friendly material and the most
complex 3D structure printing. This section introduces abundant biopolymer on Earth [168] . Hydroxyethyl cellulose
three representative rheological additives currently used in has many hydroxyl groups, which determine hydrophilicity
extrusion-based bioprinting. and capacity for chemical modification. In regards to
bioprinting, hydroxyethyl cellulose seems to be more
3.3.1. Nanoclay suitable than methylcellulose whose methyl groups are
Nanoclay is a synthetic magnesium silicate clay, which is inert [169] . As a rheological additive, hydroxyethyl cellulose
an inorganic material. It is widely used in the cosmetics exhibited properties similar to those of nanoclay, and they
industry and the coating industry as a rheology aid and can improve printability for self-supporting bioprinting [170] .
film-forming additive [159] . The degradation products of
nanoclay are non-toxic and even have a positive effect on 3.3.3. Guar gum
bone metabolism and calcification [160] , and have a great Guar gum is a water-soluble natural polysaccharide
potential in tissue engineering applications. Nanoclay, produced from endosperms of leguminous plants, which
which is sensitive to viscosity shearing, is able to be comprise mannose and galactose [171] . Owing to extensive
quickly sheared and thinned and to restore the structure hydrogen bonding between galactose units and water,
after shearing. This good thixotropy endows it with guar gum solution has high viscosity in cold water even
good performance as an extrusion-based printing ink, with low concentrations. Compared to other natural
and encourages extensive application of nanoclay in 3D gums, guar gum is cheaper. It is mainly used as thickener
bioprinting, even 4D printing [161,162] . However, nanoclay and stabilizer in industry. Guar gum forms a viscous
is a dispersion system in aqueous solution, not a solution colloidal dispersion in water and shows pseudoplastic
system. The addition of low-concentration nanoclay and shear-thinning behavior, fulfilling the requirements
to other polymer gels can cause deposition and result of extrusion-based printing biomaterial ink. Blending
in blockage of the printing nozzle. Moreover, nanoclay guar gum with bioactive biomaterial inks can improve
existing as nanoparticles will fill the internal pores of gels, the printability. Blending of guar gum and chitosan at
and further affect their swelling properties [124] , reduce the acid pH was printed in rectangular membrane structure
permeability of active factors [163] , and ultimately affect the at 37°C and then neutralized and gelled by immersing it
[74]
nutrient delivery of embedded cells. Thus, nanoclay is not in sodium hydroxide solution . By adding guar gum into
suitable to be used as cell embedding biomaterial inks, but 10% gelatin solutions, the tanδ value, the ratio of G”/G’,
is only applicable for printing scaffolds without cells. increased over 0.151, which is an ideal requirement for
the filament formation . Meanwhile, the increased gel
[75]
3.3.2. Cellulose derivatives strength is able to control the structural integrity of the
Nanocellulose is a derivative of cellulose with high zero printed constructs.
shear viscosity and strong shear thinning performance
and is widely applied in extrusion-based bioprinting and 4. Modification of biomaterial ink
4D printing [161,164] . A problem with using nanocellulose is
the nozzle blockage due to its colloidal water dispersion Although extrusion-based biomaterial ink can be used
and the fact that it is undissolved in water at the molecular to generate structurally and mechanically well-integrated

Volume 9 Issue 2 (2023) 13 https://doi.org/10.18063/ijb.v9i2.649