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Discovering new 3D bioprinting applications: Analyzing the case of optical tissue phantoms
“3D fabrication technology used to precisely dispense minimum variation over time in their properties , as
[27]
cell-laden biomaterials for the construction of complex any change in the phantom could be interpreted as an
3D functional living tissues or artificial organs,” using an alteration in the performance .
[25]
additive manufacturing strategy by depositing substrates Most phantoms that have been used in laboratories are
such as living cells, nucleic acids, drug particles, proteins, based on materials that do not entirely reflect the optical
and other biological components . properties, heterogeneities, or complex, multilayered
[8]
Recently, 3D bioprinting has gained significant structures of biological tissues [27,28] . In addition, the
attention , having wide utility in various areas of methodologies that have been proposed for their
[9]
medicine, it enables the fabrication of living tissue development generally consume a great amount of time,
with precise digital control . In addition, the and the optical properties of the produced phantoms present
[10]
interest of academia and industry in 3D bioprinting significant variations . In general terms, phantoms have
[28]
is growing . The applications of 3D bioprinting been developed in a single-layer way, with homogeneous
[11]
have spread from the development of tissue models optical properties that do not entirely reflect the complex
for research, drug discovery, and toxicology to the behavior of biological tissue. Researchers’ goal is to build
[12]
possibility of developing functional tissues and organs multilayered phantoms with heterogeneities that better
for transplantation . Specifically, bioprinted models mimic the structure of biological tissues . The most
[22]
[4]
give a better understanding of physiological processes, commonly used methods of producing multilayer and
including the mechanisms that can produce diseases, as heterogeneous phantoms are mold multilayer curing ,
[30]
well as those that are part of the prevention, detection, and integration after mold casting, and spin coating .
[31]
treatment of those illnesses [13-16] . Some future challenges Not only the methodologies used to create optical tissue
for 3D bioprinting are related to technical factors, such as phantoms are important but also the materials play a key
improving its resolution and printing speed, in addition to role. Phantom matrices represent >95% of the total volume
increasing the number of available materials to better of the phantom, and consequently, they have the most
[12]
mimic the biological, structural, mechanical, and even significant effect on its applications. Liquid, gelatinous,
optical characteristics of organs and biological tissues . or solid substances can be used as phantom matrices [22,32] .
[17]
Biophotonics concerns the study of the interaction of These materials are selected according to their properties,
visible light and biological systems . It is commonly including their stability over time . Gelatinous materials
[22]
[18]
used in medicine to study biological tissue to detect, have been shown to be the most viable option for the
diagnose, and treat diseases in a minimally invasive or development of phantoms because they have thermal and
non-invasive way [19,20] . Biophotonics techniques have mechanical properties that closely match those of biological
been shown to be less harmful than are other biomedical tissue [26,29] and their lifetime is longer than that of phantoms
techniques that use ionizing radiation, such as X-rays . composed with liquid substances . They also allow the
[22]
[21]
The light-biological tissue interaction is mediated integration of a wide variety of substances to simulate both
through the optical characteristics of the biological optical and biochemical properties [22,26,33] , making gelatinous
medium. These characteristics are related to how the light materials ideal for biophysical studies and generating
travels and propagates through the biological medium complex structures. Gelatins and agarose are commonly used
(refractive index and scattering coefficient) and how it is materials that have been adopted in many laboratories since
absorbed by the medium (absorption coefficient), factors the mid-1990s . Thereafter, methods for the elaboration of
[22]
that determine the biological tissues’ unique behavior in phantoms have usually been carried out by hand.
response to light. To mimic these properties, objects known Further technological advances have occurred,
as optical tissue phantoms have been used in biophotonics especially in the development of hydrogels, which began
research and development (R&D) . A typical phantom to be studied in the late 1990s for their use as phantom
[22]
consists of a base material, scattering, and absorber matrices . Hydrogels are biocompatible materials; they
[26]
materials, and sometimes contrast enhancement agents, resemble tissue extracellular matrix and replicate some
[34]
such as fluorophores [23,24] . Optical tissue phantoms have physicochemical properties of biological tissues , and
[35]
been used as calibrators aiming to establish global they can be used for drug delivery. This application is
standards for the measurement of biomedical techniques extremely attractive for enhancing phototherapies, such
like imaging . Moreover, they have been utilized for the as photodynamic therapy [36-38] . These phototherapies
[24]
development of new techniques and prototypes for the require the application of a substance known as a
diagnosis and treatment of diseases; furthermore, they are photosensitizer before irradiation with light for treating
suitable for clinical trials, as well as for the improvement, various diseases . Hydrogels can carry diverse types of
[39]
and routine quality control of prototypes [14-16,23,24,26] . Also, photosensitizers to the target cells more effectively than
it is important to implement standardized protocols for the methods that are commonly used at present can .
[36]
the development of phantoms because they must present Among the hydrogels, polyvinyl alcohol (PVA) gel
2 International Journal of Bioprinting (2019)–Volume 5, Issue 1