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The trend towards in vivo bioprinting

tions of natural tissues such as sweat glands in the 3. Challenges in Translating in vitro Bioprinting
skin. This reflects the fact that quite a few challenges to in vivo
facing current bioprinting techniques remain unsolved.
For in vivo bioprinting, even more challenges arise Some of the aforementioned in situ hydrogel therapies
when adapting knowledge gained through in vitro only rely on the microstructures of hydrogels to faci-
systems and the repair of superficial tissues/organs to litate vascularization within the fills, which was un-
the in vivo repair of internal organs. Firstly, the size of fortunately not effective enough for large-sized con-
the printing units must be minimized to comply with structs. The capability to create precise structures,
the increasingly-popular minimally invasive surgical particularly to establish micro-vascular and interstitial
techniques. This can be extremely challenging for networks within the printed tissues/organs, is crucial
some biofabrication techniques whose setups require to the promotion of effective self-assembly and self-
large amounts of external instruments. Secondly, the organization of cells, and to the success of bioprin-
demands of in vivo environments of internal tissues/ ting [14] . Therefore, biofabrication plays an important
organs are complex and may not be conducive to role in bioprinting not only as cell delivery tools, but
formation of existing biomaterial constructs due to also as an effective constructer of optimal micro- and
high moisture, high oxygen level, and dramatic macro-scale architectures. With biofabrication tech-
differences in mechanical and chemical properties of niques, micro-circulation along with macro-circulation
adjacent native tissues, which together pose new can be potentially created to allow transportation of
challenges to materials science. In addition to satis- oxygen, nutrients, and metabolic waste products. It is
fying strict requirements on biocompatibility and encouraging to witness the rapid advances in biofabri-
biodegradability for biomaterials, materials which are cation, which offer extraordinary opportunities for
suitable for in vivo bioprinting should have a rapid biotechnology to potentially realize some fascinating
polymerization and crosslinking rate (ideally a few advances, e.g. the printing of living tissues/organs.
seconds to minutes), and a capability for polymeriza- Two excellent review articles on the current states of
tion and crosslinking under a moist, oxygen-rich bioprinting technology have been published by Ozb-
condition. Last but not least, transferring bioprinting olat and his colleagues [15,16] . In brief, there are three
from laboratory to operating room requires the syn- categories of biofabrication techniques: (i) laser-based;
chronous advancement of surgical technologies, parti- (ii) inkjet-based; and (iii) nozzle-based. These have
cularly robot-assisted operation systems which allow been concurrently adapted to build in vitro bioprinting
precise micro-manipulation inside the body, to provide systems, with the potential to be fused into hybridized
reliable control over in vivo biofabrication. systems in the future. It is interesting to reassess each
The development of in vivo bioprinting therefore of these technologies with regards to their future in
involves cell biology, materials science, biofabrication, vivo applications, particularly their readiness and po-
and surgical technologies. In brief, a deep under- tential to be handled by surgeons in the operating
standing of cell behaviors forms the foundation for rooms. Here, the implementation of current bioprint-
guiding in vivo cell proliferation and functional extra- ing techniques is briefly reviewed, with comments on
cellular matrix (ECM) formation. Development of some of the techniques to envisage their possible ap-
sophisticated biomaterials, which support cells with plication for in vivo bioprinting.
physiochemically and biologically satisfying envi- 3.1 Bioprinting Techniques
ronments while facilitating fast bioprinting, will play
pivotal roles. Advanced biofabrication technologies (1) Laser-based bioprinting. Laser-based bioprinters
provide effective tools to realize the controllable con- use laser light to polymerize or solidify biomaterials
struction of new tissues/organs at the desired site. into fine structures. Laser direct writing (LDW) of
Novel surgical technologies, which allow precise con- cells is a widely used bioprinting approach, in which
trol of bioprinting devices in the operating room, are laser pulses are utilized to selectively transfer cells
final steps towards clinical application. In the next few from a donor container to the building substrate to
sections, we will review the state-of-the-art and tech- spatially pattern or construct a cell-jammed structure.
nical trends in biofabrication, biomaterials, surgical A representative of LDW is the laser induced forward
technologies and their future applications to in vivo transfer (LIFT) bioprinter. The setup of a LIFT-based
bioprinting. bioprinter typically comprises of three working units:

18 International Journal of Bioprinting (2015)–Volume 1, Issue 1