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International Journal of Bioprinting 3D bioprinting for nanoparticle evaluation

models. The artificial skin model is developed through a nanocapsules (QZ/NC) within a 3D-bioprinted skin
meticulous layer-by-layer bioprinting process, involving model. This study focuses on the application of these
the alternate deposition of collagen hydrogels and nanocapsules in addressing the inflammatory processes
fibroblast cells (Figure 3A). The researchers utilized a 3D in skin diseases through PDT. The research presents
Discovery Instrument that allows precise control over a comprehensive evaluation of the physicochemical
the printing parameters, such as valve on-time ratio, air properties, stability, cytotoxicity, permeation, and
pressure, and nozzle diameter. This control is critical for cytokine modulation of QZ/NC. The QZ/NCs were
creating well-defined, consistent 3D structures that closely prepared using the nanoprecipitation method, with a
mimic the natural architecture of human skin. One of the polymer coating composed of poly(L-lactic acid-co-
significant advantages of this bioprinted skin model is its glycolic acid) (PLGA) and lecithin. These nanocapsules
ability to maintain cell viability and structural integrity demonstrated excellent compatibility, as evidenced by
over an extended period. cytotoxicity tests on HaCaT cells, showing no significant
Xu et al. demonstrated that their construct, composed toxicity at lower concentrations. The permeation
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of multiple layers of collagen and fibroblasts, remained studies utilized a sophisticated 3D-bioprinted skin
stable and functional for at least 14 days in culture. The model, designed through suspended layer additive
cells within the construct exhibited high viability rates, manufacturing, which mimics the epidermal and dermal
indicating effective nutrient diffusion and a conducive layers of human skin. Fluorescence analysis confirmed
environment for cellular activities. To validate the model’s the successful permeation of QZ/NCs across all skin
efficacy for NP screening, the research team tested the layers, highlighting their enhanced bioavailability and
penetration abilities of polystyrene NPs with different permeability in the stratum corneum.
surface charges. The study focused on hydroxyl, amine, The bioprinted skin model can simulate the in vivo
and sulfate-modified polystyrene NPs, which possess environment, thereby providing a reliable platform for
varying surface chemistries and, consequently, different evaluating the therapeutic efficacy of QZ/NCs in PDT.
penetration efficiencies (Figure 3B). The bioprinted skin This model was created using a bioink composed of
model revealed that amine-modified NPs, which are pectin and collagen, which mimic the polysaccharides
positively charged, penetrated the collagen layers more and proteins, respectively, found in native ECM. The
effectively than their negatively charged counterparts. suspended layer additive manufacturing method involved
This finding is consistent with previous studies involving using computer-aided design (CAD) to accurately
living skin tissues, suggesting that the bioprinted model replicate the complex structure of human skin, layer
accurately replicates the behavior of natural skin. The by layer. This precise bioprinting technique allowed for
bioprinting technique employed not only facilitates rapid the creation of a skin model that closely resembles the
screening of NPs but also offers a scalable and ethically actual human skin, both structurally and functionally,
sound alternative to animal testing. 53,54 By enabling the enabling accurate assessment of nanocapsule permeation
precise control of cell placement and scaffold structure, and intracellular incorporation. PDT and QZ/NCs were
bioprinting allows for the creation of complex tissue tested on this model, revealing significant enhancement
models that can be tailored to specific research needs. in drug delivery efficiency and effective intracellular drug
This flexibility is particularly beneficial for exploring the accumulation. Further experiments involved inducing
mechanisms of transdermal drug delivery and optimizing an inflammatory process in HaCaT cells using bacterial
NP formulations for therapeutic applications. Overall, lipopolysaccharide (LPS) and subsequently treating
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the study by Xu et al. highlights the potential of 3D
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bioprinting technology to revolutionize the field of them with QZ/NC and PDT. The cytokine modulation
transdermal drug delivery and NP evaluation. The was analyzed through enzyme-linked immunosorbent
artificial skin model they developed serves as a powerful assay (ELISA), which showed a notable reduction in pro-
platform for rapid, cost-effective screening, and providing inflammatory cytokines (interleukin [IL]-1β, IL-8, and
valuable insights into the interactions between NPs and monocyte chemoattractant protein-1 [MCP-1]) after PDT
skin tissue. 56 treatment. This anti-inflammatory effect was significantly
more pronounced compared to treatments with QZ/NCs
3.2. Quinizarin-loaded nanocapsules and or LED light alone. The integration of 3D bioprinting
3D-bioprinted skin model for photodynamic and nanotechnology in this study underscores the
therapy evaluation potential for developing advanced therapeutic modalities
Amaral et al. developed an approach for evaluating that overcome the limitations of current treatments for
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photodynamic therapy (PDT) using quinizarin-loaded skin inflammation. 57

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