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3D bioprinting technology for regenerative medicine applications

(PEGDMA) was successfully used to print cartilage short peptides based hydrogels was demonstrated by
construct containing human articular chondrocytes [95] . maintaining the organotypic culture of intestinal epi-
In this study, PEG has been utilized as 3D biopaper to thelial cells (Caco2) and 3D culture of stem cells. It
make constructs that repair osteochondral plugs [95] . was shown that embryonic stem cells encapsulated
(3) Poly(L-lactic acid) (PLA) within these ultrashort peptide hydrogels can retain
PLA is an aliphatic polymer with glass transition their pluripotency, using Tra-I-60, Tra-I-81, Oct4 and
temperature of 60°C and an excellent mechanical Nanog as pluripotency markers [72] . Furthermore, hu-
strength. It is a biodegradable, biocompatible and se- man mesenchymal stem cells encapsulated in these
micrystalline polymer used for various tissue engi- peptide based hydrogels differentiated into adipogenic
neering applications. As a bioink, PLA is less viscous lineage under defined culture conditions. It was pro-
in nature and can be easily ejected through the needle. posed that these peptide hydrogels can offer a suitable
After printing, PLA exhibits faster evaporation and can nanotopography and 3D microenvironment to support
provide structural integrity to the construct. Recently, organotypic culture of primary cells (gastrointestinal
an acrylonitrile butadiene styrene-PLA blend was used and skin cells) as well as 3D culture of stem cells [72,98] .
as a bioink to produce a cartilage graft [96] . Nucleus Bioinks made from these ultrashort peptides exhibit
pulposus and primary articular chondrocytes cultured interesting properties that could be useful for the de-
on this scaffold maintained their native phenotypes velopment of 3D organotypic cultures for drug scree-
over three weeks [96] . ning and biological constructs for tissue engineering
(4) Poly(ε-caprolactone) (PCL) applications in the future [100] .
PCL is a synthetic polyester which is semicrystal-
line, biocompatible and biodegradable. It is an easily 6. Applications of Bioprinting
processable bioink due to its excellent properties such Bioprinting makes use of novel bioinks and 3D print-
as low melting point, thermoplastic behavior, hydro- ing techniques to fabricate closely resembling organs/
lytic degradation and excellent mechanical proper- tissues for regenerative medicine applications. Bio-
ties [97] . Initially, PCL being a viscous solution had dif- printing techniques make it possible to print cells in
ficulties in printing because of the requirement of the constructs in specific locations which is important
large diameter nozzle and high pressure. To overcome for mimicking native tissue architecture [19] . As dis-
this problem, an electrohydrodynamic jet technique cussed in section 2, there are several structural and
was used to print PCL bioinks. Applying electrohy- functional features that are considered ideal for de-
drodynamic forces created a temperature gradient in veloping 3D constructs. Among the structural features,
the ink and high resolution (10 μm) 3D constructs were vasculature is one of the important factors that deter-
formed [97] . However, PCL cannot be used as cell-laden mine the success of bioprinted constructs by improv-
bioink due to its high melting point (60°C). Instead ing cell viability [48] . The vasculature of 3D constructs
PCL can be used to provide supporting structure in 3D is essential to improve nutrient delivery, tissue ingro-
constructs and also to reinforce stability to the fabri- wth, and regeneration [53] . Cells in tissues are mostly
cated scaffolds [9,97] . Though synthetic polymers offer found within 100-200 μm away from adjacent blood
many advantages in bioprinting, further developments vessels. Cells that are present within this limit of 100-
are required to improve the biocompatibility and de- 200 μm receive nutrition and oxygen through diffusion
gradation behavior of this class of polymers. from the nearby capillaries. Hence bioprinted 3D con-

5.3 Ultrashort Peptides structs need to be prevascularized to overcome this
diffusion limit and also to mimic the native tissue [69] .
Hauser and co-workers have recently reported that Several bioprinting approaches have been shown to
distinct peptides selected from the earlier discovered stimulate vascularization of scaffolds for tissue engi-
class of self-assembling ultrashort peptides can be neering applications [19,41,53] . For example, a 3D micro-
used as bioinks for bioprinting applications [98–100] . vascular construct was printed using human micro-
These ultrashort peptides have an innate tendency to vascular endothelial cells and fibrin as bioinks [53] . In
self-assemble into hydrogels with a nanofibrous topo- the case of cell viability, numerous studies have dem-
graphy that closely resemble collagen and thus mi- onstrated that there was no difference in cell viability
micking the native architecture of tissue ECM [72,98] . between non-printed and printed cells [48,101] . Cell via-
As an example, the biocompatibility of these ultra- bility and vasculature are some of the important para-

18 International Journal of Bioprinting (2016)–Volume 2, Issue 2