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3D bioprinting technology for regenerative medicine applications

for various biomedical applications [107,108] . These stem taining a soft part (hydrogels for loading growth fac-
cells can differentiate into specific lineages and can tors/cells) and a hard part (rigid and porous for me-
offer potential cell sources for in vitro tissue models. chanical integrity). In this study, poly-ethylene glycol
Bioprinting tissues containing stem cells could be a diacrylate (PEGDA) and poly-(ε-caprolactone) (PCL)
potential strategy to develop patient-specific tissue were used as model materials for soft hydrogel and
constructs for regenerative medicine applications. Ta- rigid scaffold, respectively. This bioprinting method
soglu et al. have described in detail the applications of involves digital light processing-based stereolithogra-
bioprinting in stem cells research [108] . Human induced phy (DLP-SLA) and molten material extrusion based
pluripotent stem cells (IPSCs) printed with alginate techniques for soft and rigid materials, respectively. It
hydrogels were allowed to differentiate into hepato- was demonstrated that the properties of this hybrid
cyte-like cells using differentiation factors. These hydrogel can be easily tailored using DLP-SLA me-
IPSCs showed better cell viability and also differen- thod and the resultant bioprint had a compressive
tiated into hepatocyte-like cells [107] . These differen- modulus (6 MPa) greater than many hydrogels. This
tiated cells were positive for hepatocyte phenotypes hybrid bioprint was reported to exhibit good cell via-
such as albumin secretion and morphology. This ap- bility and vasculature [110] .
proach may be helpful to generate patient-specific 3D Bioprinted constructs containing native ECM com-
liver constructs using IPSCs for drug screening and ponents may help to improve the cellular functions
organ transplantation [107] . such as proliferation, maturation and differentiation.
In another study, 3D bioprinting technology was To achieve this, the bioink materials can be modified/

used to create ES cells into 3D hydrogel spheroids to functionalized with ECM components. In a recent study,
maintain the stem cell pluripotency [109] . These sphe- collagen films were first grinded using a crushing-
roids were made from gelatin and alginate. In this particle desk crusher and passed through a 38μm mesh
[111]
method, ES cells laden hydrogel spheroids with con- to get collagen microfibers of length 22 ± 13μm .
trolled size and uniform pluripotency were bioprinted These collagen microfibers were linked with bone
using an extrusion-based 3D bioprinter. The cell morphogenetic protein-2 (BMP2) that contained col-
spheroids were shown to retain pluripotent stem cell lagen-binding domain (CBD-BMP2). The CBD-BMP2
markers such as Oct 4, SSEA-1 and Nanog [109] . In was printed onto bone marrow mesenchymal stem
another study, a novel bioink made from ultrashort cells-laden methacrylamide gels. It was reported that
peptide hydrogels were used to bioprint 3D structures these bone marrow mesenchymal stem cells differen-
encapsulated with human embryonic stem cells. It was tiated into osteocyte cells due to the presence of ECM
shown that embryonic stem cells encapsulated within components such as collagen and BMP-2 in CBD-
[111]
these ultrashort peptide hydrogels can retain their plu- BMP2 .
Cells are subjected to a mild stress (thermal or me-
ripotency, using Tra-I-60, Tra-I-81, Oct4 and Nanog as chanical) during bioprinting that may affect the cell
pluripotency markers [72] . This bioink was shown to viability in the printed constructs. New strategies that
have very good applications in 3D bioprinting of tis- can minimize cell stress during printing are needed to
sue constructs and organoids for applications such as further improve cell viability in bioprinted constructs.
drug screening and tissue engineering. As an example, Blaeser et al. [112] have developed a

7. Emerging Strategies in Bioprinting fluid-dynamic model to control the shear stress while
printing by optimizing nozzle diameter, bioink viscos-
Recent advancements in 3D printing methods and ity, and extrusion pressure. In another study, micro-
bioink materials will enable further improvements in fluidics-based platform and bioprinting technology
the 3D bioprinting technology. Modified and new were combined to print constructs using low-viscosity
printing methods are being employed to design better bioink (a blend of alginate and gelatin methacroyl
quality bioprints with improved properties suitable for (GelMA)), which resulted in visible cell viability via
organ engineering. Novel bioink materials such as minimizing the shear stress during bioprinting [112] .
ultrashort peptides and hybrid polymeric materials are Extra-hepatic transplantation of islets cells using
promising candidates for 3D bioprinting of tis- biomaterials may be useful in glycemic correction of
sues/organs. For instance, Shanjani et al. [110] devel- insulin dependent diabetic patients [114] . Marchioli et
oped a hybrid bioprinting method using polymer con- al. [114] bioprinted 3D structures using a bioink solution

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