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REVIEW ARTICLE

Of balls, inks and cages: Hybrid biofabrication of 3D

tissue analogs

Nicanor I. Moldovan *, Leni Moldovan , Michael Raghunath 3,4
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1 Departments of Biomedical Engineering, Indiana University - Purdue University at Indianapolis, Surgery, IU School of
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Medicine, Indianapolis, IN, 46202, USA, Center for Cell Biology and Tissue Engineering, Institute for Chemistry and
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Biotechnology, Competence Center TEDD, Zurich University of Applied Sciences, CH - 8820 Wädenswil, Switzerland
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Abstract: The overarching principle of three-dimensional (3D) bioprinting is the placing of cells or cell clusters in the 3D
space to generate a cohesive tissue microarchitecture that comes close to in vivo characteristics. To achieve this goal, several
technical solutions are available, generating considerable combinatorial bandwidth: (i) Support structures are generated first,
and cells are seeded subsequently; (ii) alternatively, cells are delivered in a printing medium, so-called “bioink,” that contains
them during the printing process and ensures shape fidelity of the generated structure; and (iii) a “scaffold-free” version of
bioprinting, where only cells are used and the extracellular matrix is produced by the cells themselves, also recently entered
a phase of accelerated development and successful applications. However, the scaffold-free approaches may still benefit from
secondary incorporation of scaffolding materials, thus expanding their versatility. Reversibly, the bioink-based bioprinting
could also be improved by adopting some of the principles and practices of scaffold-free biofabrication. Collectively, we
anticipate that combinations of these complementary methods in a “hybrid” approach, rather than their development in
separate technological niches, will largely increase their efficiency and applicability in tissue engineering.
Keywords: Tissue engineering, scaffolds, scaffold-free, bioprinting

*Correspondence to: Nicanor I. Moldovan, “Richard L. Roudebush” VA Medical Center, Indiana University - Purdue University at Indianapolis,
1481 W. 10 St. Room C6128, Indianapolis, IN 46202. Tel.: 317-988-2337; nimoldov@iupui.edu
th
Received: October 31, 2018; Accepted: November 28, 2018; Published online: December 26, 2018

Citation: Moldovan NI, Moldovan L, Raghunath M, 2019, Of balls, inks and cages: Hybrid biofabrication of three-dimensional
tissue analogs. International Journal of Bioprinting, vol.5(1): 167. http://dx/doi.org/10.18063/ijb.v5i1.167

1. Biofabrication of Tissue Analogs - The shared to create synergies with an eclectic mix of techniques
Main Approaches for reaching specific goals. In future, the combined use
of the main approaches in biofabrication will likely lead
Biofabrication, the three-dimensional (3D) assembly of to more “hybrid” systems and subsequent expectations
living cells in structured systems , has evolved in the past on appropriate instrumentation . For this reason, in our
[1]
[8]
decades as the biological facet of additive manufacturing . overview, we will discuss the strengths and weaknesses of
[2]
Technically, biofabrication can be roughly divided into
“bioprinting,” a technology akin to the classical use of these approaches, according to their main features. [9]
[1,4]
[3]
[4]
ink and paper , and “tissue assembly” , where other Moroni et al., Groll et al. and Moldovan have
techniques such as “tissue strands” [5] , lamination of noticed some confusion regarding the terminology in this
“cell sheets” or cell spheroid piercing-and-stringing , field. Therefore, here we need to specify again what - in our
[7]
[6]
have recently evolved. The purpose is to assemble cells opinion - 3D Bioprinting is not: namely, it is not the mere
into a living, functional system that serves for in vitro additive manufacturing (a.k.a. 3D printing) of implantable
drug development and substance testing, or as an in vivo materials which, by all intents and purposes, would be
implantable tissue . However, the boundaries between “biomaterials” [10] . The implantation of such a material
[1]
approaches are blurring, because they will be increasingly aims either at total immunological inertia (sometimes
Of balls, inks and cages: Hybrid biofabrication of 3D tissue analogs © 2019 N I. Moldovan , et al. This is an Open Access article distributed under the
terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), permitting all non-
commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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