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International Journal of Bioprinting                              Bioprinted skin scaffolds with GNP exposure




            media. This further prevents opsonization, making   the accumulation and retention of the GNPs. Furthermore,
            nanoconjugates more biocompatible and increasing   there were some other additional structures in the natural
            their circulation time in vivo.  GNPs are widely used in   skin, such as elastic fibers and appendages, which may
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            the wound healing process for the delivery of drugs and   block the absorption of GNPs. Further studies could also
            antimicrobial agents. 18,38  Current studies mainly focus on   focus on the dynamic behavior of different functional
            GNP penetration and percutaneous delivery on natural   nanomaterials and the investigation of the long-term
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            skin. 39–42  Thus, GNP-conjugated drug delivery through   health effects.  Besides, adopting GNPs of certain sizes
            3D-bioprinted  scaffolds is  crucial  in wound  healing   and observing GNP deposits at specific post-injection time
            and warrants further  exploration.  Several studies  have   points may be crucial for GNP accumulation. However, the
            elucidated how GNPs, commonly used in molecular    exact binding position of the GNPs to the scaffold, as well
            diagnostics and drug delivery applications,  interact with   as the aggregation and deposition mechanism of GNPs, is
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            collagen. 43,44  In recent studies, the mechanical stability   still unknown. Further studies may extend to evaluate the
            and diffusion characteristics of gel interconnection and   binding mechanism of GNPs to the scaffold at a subcellular
            hindrance of GNPs  in vitro were investigated.  Further,   level.  Additionally,  clinical  applications of  the cell-laden
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            the  incorporation of GNPs into crosslinked scaffolds   scaffold could be advanced by: (i) serving as a potential
            enhanced their stability against enzymatic degradation   material to absorb and excrete toxic GNPs, and (ii) a
            and increased the tensile strength, promoting the wound   targeted site to accumulate GNP-delivered drugs.
            healing process.  In another study, increased concentration
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            of GNPs enhanced the free radical inhibition effect of the   5. Conclusion
            skin substitutes.  However, these studies only focused   In the present study, 3D bioprinting was applied to fabricate
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            on the inherent percutaneous penetration of GNPs from   cell-laden scaffold composites as skin substitutes. After
            the scaffold. In our study, after systematic administration   intravenous administration, the accumulation of GNPs on
            of GNPs, we noted GNP accumulation tendency in our   the skin scaffolds exceeded that in natural skin and other
            scaffold in vivo, exceeding natural skin and other organs.   organs, indicating the strong tendency of the skin scaffolds
            As chronic wounds require a long recovery process,   to absorb GNPs. Thus, 3D-bioprinted skin scaffolds could
            drugs with a short half-life may not adequately meet the   be utilized to enhance the understanding of nanoparticle
            treatment needs for single-use applications. However,   biodistribution  in vivo, reducing the need for animal
            frequent changes in the transplanted drug-incorporated   skins. Furthermore, they can be employed as a potential
            scaffolds may cause further damage to the wounds. Thus,   method to absorb and excrete nanoparticles after systemic
            intermittent systematic administration of drugs with a   exposure and as a targeted site for the accumulation of
            short half-life may be a promising strategy. Future studies   GNP-delivered drugs.
            could focus on how GNP-delivered drugs can enhance the
            recovery process and ameliorate inflammatory response   Acknowledgments
            following cell-laden scaffold transplantation.     None.
               As the use of GNPs expands, concerns about toxicity
            and biosafety have gained significant attention.  Notably,   Funding
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            the skin is an important site of nanoparticle accumulation   This work was supported by the STI2030-Major Projects
            following systemic administration.  Besides, in vivo skin   (2022ZD0205202), the Anhui Province University Scientific
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            penetration of quantum dot nanoparticles was reported.    Research Project (KJ2021A0212, 2022AH051169), the
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            However, the  in vivo biodistribution of GNPs within   Anhui Medical University Research Funding (2021xkj008),
            collagen remains unclear. In this study, 3D-bioprinted skin   the University Synergy Innovation Program of Anhui
            scaffolds,  despite  being  thick  and  abundant  with  seeded   Province (GXXT-2022-030), and the College Students’
            cells, exhibited higher GNP accumulation than natural   Innovation and Entrepreneurship Training Program of
            skin and other organs after intravenous administration,   Anhui Province (S202210366019).
            indicating a strong tendency for cell-laden scaffolds to
            absorb GNPs. The differences in GNP accumulation and   Conflict of interest
            absorption  may  be  due  to  the  microstructure  between
            natural skin and skin scaffolds. The dermis of natural   The authors declare no conflict of interest.
            skin  appeared densely arranged  and  overlapping under
            scanning electron microscopy (SEM).  However, the   Author contributions
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            microstructure of the collagen-based scaffold was porous   Conceptualization: Chenwei Wang, Xinmeng Wang,
            under SEM.  The porous structure of collagen may induce   Xinya Qin
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            Volume 10 Issue 6 (2024)                       440                                doi: 10.36922/ijb.4692
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