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International Journal of Bioprinting 3D bioprinting for nanoparticle evaluation

various experiments to assess the impact of SLNs on prepared both 2D cell models and 3D tumor spheroids to
glioblastoma treatment. The SLNs were loaded with the evaluate how the modifications to the LNPs affected their
model anticancer drugs paclitaxel and sorafenib, and their in vitro cytocompatibility.
cellular uptake and penetration were confirmed through The bioprinted tumor spheroids were generated using
fluorescence microscopy analysis. Notably, the SLNs were magnetized cancer cells (PC3-MM2, MDA-MB-231, and
effectively delivered to tumor cells, significantly reducing A549) that aggregate under a magnetic drive. During
cell viability and demonstrating superior results compared this process, cells were magnetized using NanoShuttle-
to free drugs. PL and cultured in ultra-low attachment 96-well plates to
A key aspect of the study was the use of 3D bioprinting form spheroids via the magnetic drive. For cytotoxicity
technology to create glioblastoma models. The researchers evaluation, various human cancer cell lines (PC3-MM2,
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used a human glioblastoma cell line (U87-MG) to produce MDA-MB-231, and A549) were used as the 2D cell models,
3D tumor spheroids. This was achieved by magnetizing the being exposed to LNPs at concentrations up to 500 µg
−1
cells, then placing them in ultra-low attachment 96-well mL for 24 hours. In the 3D spheroid model, the cells were
−1
plates, and using a magnetic drive to aggregate the cells exposed to LNPs at concentrations up to 100 µg mL for
into spheroids. To evaluate the penetration of SLNs into the 48 hours to assess cytotoxicity. The results showed that
tumors, the NPs were labeled with a fluorescent dye (DiA) LNP-DSS significantly increased cellular uptake compared
and observed using confocal fluorescence microscopy. The to non-functionalized LNPs and LNPs functionalized with
researchers incubated the DiA-labeled SLNs with the 3D 9-amino acid cyclic peptide (iRGD). The cellular uptake
spheroids for 6 and 24 hours, capturing images at each time rates differed between the 2D and 3D models. In the 2D cell
point to visualize the extent and depth of SLN penetration model, sedimentation and diffusion effects led to higher
into the tumor spheroids. Cytotoxicity assays showed that cellular uptake rates, whereas, in the 3D spheroid model,
SLNs loaded with paclitaxel and sorafenib reduced cell stronger and more realistic cell-cell interactions resulted
viability more effectively than the free drugs. This indicates in lower uptake rates. This difference is attributed to the
that SLNs are more efficiently delivered to tumor cells, 3D model’s ability to better replicate the realistic tumor
maximizing the therapeutic efficacy of the drugs. The microenvironment, thereby providing a more accurate
effectiveness of SLNs in drug delivery was particularly representation of NP-cell interactions. 46
evident in the 3D spheroid models, where the penetration
and therapeutic impact of the SLNs were significantly 3. Three-dimensional bioprinted skin
greater compared to free drugs, demonstrating the ability tissue models
of SLNs to deliver drugs deep into the tumor tissue. The Skin tissue models are essential tools in dermatological
study by Arduino et al. demonstrates that SLNs produced research and pharmaceutical development, providing
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via microfluidics, evaluated in sophisticated 3D-bioprinted a means to study skin physiology, disease mechanisms,
tumor models, hold great promise for the effective delivery and the efficacy of topical treatments. 47,48 These models
of anticancer drugs. range from simple 2D cell cultures to more complex 3D
constructs that better replicate the structural and functional
2.7. Evaluating nanoparticle uptake in properties of human skin. 12,49,50 Advanced models can
bioprinted tumor spheroids using functionalized
lignin nanoparticles include multiple cell types and layers, mimicking the
Figueiredo et al. explored the application of bioprinting epidermis and dermis to offer more accurate predictions of
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47,51,52
techniques to develop a 3D tumor spheroid model skin responses. Such models are crucial for evaluating
transdermal drug delivery systems, cosmetic products, and
for evaluating the cellular uptake and efficacy of therapeutic NPs, helping to reduce the reliance on animal
functionalized lignin NPs (LNPs). These LNPs are testing and accelerate the development of new treatments.
functionalized with a dentin phosphophoryn-derived
peptide (DSS) to enhance cellular uptake, particularly 3.1. Utilization of 3D bioprinting for evaluating
for cancer treatment applications. The study begins transdermal nanoparticle penetration
with the synthesis of carboxylated lignin to prepare the Xu et al. presented a groundbreaking study on the use
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LNPs using a solvent exchange method. The LNPs are of 3D bioprinting technology to construct an artificial
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characterized by their size, polydispersity index, and zeta skin model for assessing the transdermal penetration
potential, demonstrating stable spherical NPs suitable for capabilities of NPs. This innovative approach aims to
biological applications. EDC/NHS coupling chemistry was overcome the limitations of traditional methods, which
then used to functionalize the LNPs with DSS, resulting often rely on scarce human skin tissues or costly and
in DSS-functionalized LNPs (LNP-DSS). The researchers time-consuming animal models, particularly porcine

Volume 10 Issue 5 (2024) 9 doi: 10.36922/ijb.4273