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International Journal of Bioprinting                                3D bioprinting for nanoparticle evaluation




            9. Three-dimensional bioprinted drug               significantly enhanced fibroblast viability and provided
            release model                                      protection against oxidative stress, with optimal results at
                                                               specific MH loading concentrations.
            The evaluation of drug release profiles and their impact on
            cellular environments is crucial for developing effective   Scanning electron microscopy (SEM) was employed to
            therapeutic strategies. 116–118  This section explores various   visualize the internal microstructure and distribution of the
            methodologies used to study drug release from NP-  MH-DS NPs within the GelMA matrix. The NPs formed
            based systems within 3D-bioprinted models. Advanced   clusters within the GelMA network, ranging in size from 50
            bioprinting techniques enable the creation of complex in   to 120 nm. The controlled release profile was attributed to the
            vitro environments that closely mimic in vivo conditions.   interactions between the MH-DS complexes and the charged
            Specifically, 3D bioprinting excels in replicating cell-cell   networks within the GelMA, which facilitated sustained
            and cell-matrix interactions, allowing for more accurate   release by reducing the initial burst effect observed with
            assessments of NP drug release and cellular responses. 119–121    directly mixed MH (Figure 9B). The study conducted by Fu
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            These studies highlight the importance of optimizing   et al.  showcases the versatility and efficacy of GelMA bioinks
            bioprinting parameters and materials to advance preclinical   in 3D bioprinting applications. The ability to control the release
            drug testing and therapeutic applications.         kinetics  of  MH  through  NP  encapsulation  and  optimize
                                                               printing parameters for high cell viability underscores the
            9.1. GelMA bioinks for evaluating nanoparticle-    potential of this approach for developing advanced in vitro
            based minocycline release and cellular protection  models for cancer research and NP evaluation. The findings
            Fu et al.  conducted a study utilizing bioinks to develop   indicate that GelMA-based bioprinted constructs can provide
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            a  3D-bioprinted  model  for  evaluating  the  release  and   a more accurate representation of the in vivo environment,
            protective effects of minocycline (MH)-loaded NPs under   thus  improving  the  reliability  of  preclinical  evaluations  of
            oxidative stress conditions. This research underscores the   NP-based therapies. 123
            significant potential of 3D bioprinting in creating in vitro
            models that closely mimic the in vivo environment for more   10. Three-dimensional bioprinting in tissue
            accurate NP evaluation. The study focused on leveraging   engineering and regenerative medicine
            the thermoresponsive and photocrosslinking properties of
            GelMA to create a suitable bioink for extrusion bioprinting.   The field of tissue engineering and regenerative medicine
            The primary challenge addressed was the time- and   has experienced significant advancements, particularly
            temperature-dependent flow behavior of GelMA, which   through  the  integration  of  nanotechnology  and 3D
            affects its printability and cell viability. By optimizing the   bioprinting. These innovations have paved the way for
            extrusion  printing  process,  the  researchers  successfully   the development of complex, functional tissues and
            printed GelMA constructs with high fidelity and cell survival   organs that can potentially replace damaged or diseased
            rates. They determined the optimal GelMA concentrations   ones. 124,125  Nanoparticles have become a cornerstone in this
            and printing conditions to achieve this balance.   field due to their unique properties, such as high surface
                                                               area, tunable size, and the ability to carry therapeutic
               Minocycline, known for its anti-inflammatory and   agents.  When combined with 3D bioprinting, NPs can
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            neuroprotective properties, was incorporated into dextran   be precisely incorporated into biocompatible scaffolds,
            sulfate (DS)-based NPs (MH-DS complexes) to overcome   enhancing their structural and functional capabilities.
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            the issues of burst release and lack of sustained drug   This synergy between nanotechnology and bioprinting
            delivery commonly seen with direct MH incorporation.    not only improves the efficacy of tissue regeneration but
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            The  MH-DS  complexes  were  then encapsulated  within   also allows for the creation of customized, patient-specific
            the GelMA bioink (Figure 9A). The resulting 3D-printed   implants and wound dressings. 128–130  The ongoing research
            constructs demonstrated significantly reduced initial   focuses on optimizing the synthesis and functionalization
            burst release and prolonged drug release over several   of NPs, developing novel bioinks, and refining bioprinting
            days, as compared to directly mixed MH in GelMA. The   techniques to achieve better integration and performance
            researchers utilized a dual-nozzle extrusion bioprinter   of engineered tissues.
            to create a two-layered in vitro model. The bottom layer
            consisted of fibroblasts printed with 5% GelMA, while   10.1. Bioprinted hydrogel scaffolds for evaluating
            the top layer was printed with 10% GelMA containing the   the efficacy of catechol-functionalized nanoparticles
            MH-DS complexes. This model was subjected to oxidative   in wound healing
            stress using hydrogen peroxide to simulate cellular damage.   Puertas-Bartolomé  et  al. 131  developed  catechol-
            The study found that the released MH from the NPs   functionalized NPs and applied them in 3D bioprinting



            Volume 10 Issue 5 (2024)                        21                                doi: 10.36922/ijb.4273
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