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International Journal of Bioprinting 3D bioprinting for nanoparticle evaluation

in advancing therapeutic strategies, including cancer treatment, vascular repair, and drug delivery systems. Overall, by
providing selected examples to illustrate the concepts, this comprehensive review underscores the importance of 3D
bioprinting as an innovative platform for nanoparticle research, bridging the gap between traditional 2D cell cultures
and in vivo studies, and contributing to the development of nanomedicines and personalized medical treatments.

Keywords: 3D bioprinting; Nanoparticles; Disease models; Antitumor effects; Drug delivery

1. Introduction growth patterns, and signaling pathways. Conversely, 3D
environments allow for more natural and complex cell
In recent years, particularly since the early 2000s, three- signaling interactions. 14,15 Additionally, in 2D cell cultures,
dimensional (3D) bioprinting technology has achieved drug or NP penetration is straightforward and typically
significant advancements in the fields of life sciences and contacts only one side of the cells, limiting the depth
medicine. This technology, which can precisely mimic the and distribution of penetration. In 3D cultures, however,
complex structures and functions of biological tissues, is drugs or NPs can be distributed throughout the entire cell
garnering considerable attention. Unlike traditional 2D structure, reflecting the drug distribution patterns in actual
cell culture methods, 3D bioprinting creates constructs human tissues. This enables more accurate assessments of
that more accurately recapitulate the actual human body drug efficacy and toxicity. 16,17
environment. 2D cell culture methods are known for
1,2
their simplicity and reproducibility, but they fall short Recent studies indicate that 3D bioprinting can be
in replicating the complex cell-to-cell interactions and used to develop various disease models, including tumor
tissue structures that occur in vivo. This limitation often models, vascular models, and multifunctional models, to
undermines the reliability of experimental results in evaluate the effectiveness and safety of NPs. For example, in
drug development and nanoparticle (NP) evaluation. In tumor models, the efficacy of NPs can be assessed through
contrast, 3D bioprinting addresses these issues by stacking the evaluation of anti-tumor effects, gene expression
cells and biomaterials layer by layer to form 3D structures analysis, and cytotoxicity comparisons between 2D and
that closely resemble actual tissues. For instance, a 3D models. 18–20 In vascular models, the technology can be
3–6
research team at Utrecht University has developed a used to evaluate vascular regeneration through targeted
novel volumetric 3D bioprinting technique to rapidly drug delivery, the prevention of restenosis, and the repair
produce high-resolution liver tissues. This method, which of ischemic injuries. 21–23 Furthermore, 3D bioprinting
projects 2D light patterns onto photoresponsive hydrogels can enhance the relevance of in vitro studies by utilizing
containing cells, allows for the quick formation of tissues. various types of bioinks and cells to mimic specific tissues
24
This research has made significant strides in enhancing and diseases. The integration of NPs with 3D-bioprinted
the detoxification function of liver tissues, contributing models shows significant potential for advancements in
substantially to the development of patient-specific models therapeutic strategies, such as cancer treatment, vascular
and new drug research. 7 repair, and drug delivery systems. 1–3,5,6,25
Three-dimensional bioprinting technology can In summary, 3D bioprinting technology has
precisely replicate the form and function of tissues using established itself as a crucial tool in NP research, providing
bioinks with various biological and physical properties. new directions and applications for future studies. The
This capability holds significant potential, particularly in continued development and application of 3D bioprinting
NP research. NPs play a crucial role in diverse biomedical are poised to significantly advance the development of safe
applications, including drug delivery, diagnosis, and and effective NP-based therapies.
therapy, and yet more accurate models are needed to In this review, we focus on the recent advancements in
evaluate their efficacy and safety. 8–10 Compared to 2D 3D bioprinting technology for NP evaluation. Specifically,
systems, 3D culture systems offer several important we cover progress achieved in the last decade, providing
advantages for NP research. In 2D cultures, cells grow selected references to highlight the main concepts and
attached to a flat surface, limiting cell-cell interactions. In significant developments. The review is structured into
contrast, 3D cultures provide an environment where cells several sections: first, an overview of the current state of
can grow and interact in all directions, better replicating 3D bioprinting technology; second, detailed applications
the complex, physiologically relevant microenvironments in disease models such as cancer, skin, vessel, and bone;
found in vivo. 11–13 The spatial arrangement in 2D cultures and third, an exploration of the integration of NPs with
restricts cell interactions, affecting cell morphology, these bioprinted models (Tables 1–3). Each section aims

Volume 10 Issue 5 (2024) 2 doi: 10.36922/ijb.4273