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Choudhury D, et al.

constructs inside body (c) mismatch between the shape
of the prefabricated construct and the actual defect and
(d) maturation of the construct in a bioreactor before
implantation. A possible solution is in vivo bioprinting
(used interchangeably with in situ bioprinting), which
will involve the de novo tissues/organs to be directly
printed and positioned at the wound/defect site. This
method would be highly effective in the treatment
of tissues/organs that can be easily arrested and
immobilized during bioprinting, e.g., the musculoskeletal
system, craniofacial skeletal defects etc. For this to come
true, portable bioprinters need to be designed and tested.
There have already been some efforts in this direction,
including the development of a hand-held bioprinting
Figure 9. Various print heads in current commercial bioprinters device called BioPen [113,114] and the concept of Robotic
arm based printer [115] .
newly lab-developed 3D bioprinting technique called 3. conclusion
freeform reversible embedding of suspended hydrogels
(FRESH) can ensure printing of hydrogels in complex The advent of commercial bioprinting has revolutionized
3D structures [111] . the field of tissue engineering. Within a short span
●Incorporation of co-axial extrusion system: Co-axial we have at least 26 companies who are working in
extrusion system will facilitate simultaneous chemical bioprinting business and out of which at least 23 are
crosslinking while 3D printing. selling their bioprinters in the market. The industry now
●Scaffold-free tissues: In recent years, the notion of has a worldwide reach with companies based in almost
scaffold-free tissue engineering has gained traction [112] , all the major markets. Some of the companies also offer
utilizing the self-organization and self-assembly their bioprinters as services and others offer avenues
based approaches. Spheroid printing technologies (for for collaborations/partnerships. Hence a researcher has
example, Kenzan) are expected to be the future of a multitude of choices, either to purchase bioprinting
tissue engineering. Kenzan method does not use any system (based on his/her applications requirements and
gel (ECM) however in case of some tissues, external budgetary constraints) or to enter into collaborations
biochemical and mechanical cues may be crucial for with the company of choice or to contract out the
their development and maturation. printing process. The fact that a simple and reasonably
●Tissue maturation: Cell-material constructs need reliable extrusion-based bioprinting system is available
optimal culturing conditions in terms of the physio- for under five thousand US dollars makes it an attractive
chemical environment in order to become functional option for most of the small academic labs or individual
tissue. Currently, none of the bioprinters has any researchers.
bioreactors associated with them which can support While this is a young industry with most ground-
the printed tissue construct for further maturation. breaking developments happening only in the last 10
For successful tissue maturation and large-scale years, there has been tremendous growth. Extrusion
implantations, this needs to be given serious thought. bioprinting has emerged as the most popular choice
●Integration of inline sensors/modules: Sensors owing to its simplicity and relatively lesser costs as
could be integrated with the bioprinters for enhanced compared to other modes. There is much potential in
data gathering and analysis: During the actual printing SLA bioprinting for manufacturing of tissues, but no
process, it would be of real value to gauge real-time commercial bioprinter can do it yet; although many
measurements of parameters such as temperature of of the printers do have UV light-source for curing of
printing chamber, humidity in printing chamber, pressure hydrogels. Currently, many labs around the world are
in extruder, speed and fidelity of the printing process trying to develop non-toxic cocktails of photoinitiators
etc. Since printing process usually takes hours, dynamic and novel biomaterials/composites which could be cured
readouts using sensors can ensure remote observation around visible light wavelengths for SLA bioprinting.
and control too. The cost barrier for laser-assisted bioprinting is very
●In situ/in vivo bioprinting modules: An in vitro high, and hence so far only one company is offering
bioprinting approach may pose many inherent it. The development of first 6-axis robotic bioprinter,
limitations regarding its clinical applicability in some as well as the desktop polar coordinate-based system,
cases like (a) ethical issues (b) fixation of fragile living has only demonstrated how much flexibility and

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