Exploring the Future of Hydrogels in Rapid Prototyping: A Review on Current Trends and Limitations - Biologically Responsive Biomaterials for Tissue Engineering - page 223

micro-vascular endothelial cells (HMVEC) cells was used as “bio-ink” and sprayed
by the inkjet technology onto a fibrinogen substrate. They suggest that these
constructs show potential in building complex 3D structures. Examples of the direct
use of printer-based systems together with hydrogels are rather limited. In some
cases, the use of an indirect system is mentioned.
Sachlos et al. [ 230 ] use an indirect approach to produce collagen scaffolds with
predefined and reproducible complex internal morphology and macroscopic shape
by developing a sacrificial mould, using 3D printing technology. This mould is then
filled with a collagen dispersion and frozen. The mould is subsequently removed by
chemical dissolution in ethanol and a solid collagen scaffold was produced using
critical point drying.
Yeong et al. [ 231 ] also utilized a similar indirect approach to fabricate collagen
scaffolds. In addition, they investigated different drying routes after removal of the
sacrificial mould with ethanol. The effects of a freeze drying process after immer-
sion of the scaffold in distilled water and critical point drying with CO 2 re fl ected
onto dimensional shrinkage, pore size distribution and morphology in general.
Boland et al. [ 223 ] described the use of the inkjet printing technique for the con-
struction of synthetic biodegradable scaffolds. They used a 2 % alginic acid solu-
tion, a liquid that is known to crosslink under mild conditions to form a biodegradable
hydrogel scaffold. The ink cartridge was filled with 0.25 M calcium chloride (CaCl 2 ),
which is known to promote the crosslinking of the individual negatively charged
alginic acid chains resulting in a 3D network structure. This crosslinker was printed
onto liquid alginate/gelatin solutions.
The biggest obstacles for RP technologies, thus also printer-based systems, are
the restrictions set by material selection and aspects concerning the design of the
scaffold's inner architecture. Thus, any future development in the RP field should be
based on these biomaterial requirements, and it should concentrate on the design of
new materials and optimal scaffold design [ 17 ]. The selected scaffold material must
be biocompatible, compatible with the printing process, and it must be easily manu-
factured in the form required (powder or liquid) [ 232 ]. In the case of powder mate-
rial, the particle size must be controllable. Another issue is the sterility of the
manufacturing process and products and their ability to withstand sterilization pro-
cesses [ 16 ]. Of course, this plays a pivotal role for all systems when embedding
cells during the process.
Some limitations are caused by material trapped in small internal holes. These
trapped liquid or loose powder materials may be difficult or even impossible to
remove afterwards, and in some cases, these residues may even be harmful to cells
and tissues. Experimental results show that the smoother the surface generated, the
easier the removal of trapped material [ 16, 17 ]. Smoother surfaces are on the other
hand less desirable for cell adhesion purposes.
Limitations of 3DP include the fact that the pore sizes of fabricated scaffolds are
dependent on the powder size of the stock material. As such, the pore sizes available
are limited to smaller pore values (<50 mm) widely distributed throughout the scaf-
fold. More consistent pore sizes, including larger pores, can be generated by mixing
porogens (of pre-determined sizes) into the powder prior to scaffold fabrication.