AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.4692
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RESEARCH ARTICLE

Evaluation of 3D-bioprinted skin scaffolds in mice along with gold nanoparticle exposure

Yi Wang1,2 ,  Xin Ma1,3 ,  Xu Wu4 ,  Shuaideng Wang1 ,  Peng Peng1,2 ,  Guozhang Tang1,3 ,  Xinya Qin5,6 ,  Xinmeng Wang7* ,  Chenwei Wang1* ,  Jiangning Zhou5
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1 School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
2 First School of Clinical Medicine, Anhui Medical University, Hefei, Anhui, China
3 Second School of Clinical Medicine, Anhui Medical University, Hefei, Anhui, China
4 Chinese Academy of Sciences Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China
5 Institute of Brain Science, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
6 Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, Anhui, China
7 Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
IJB 2024, 10(6), 4692 https://doi.org/10.36922/ijb.4692
Submitted: 29 August 2024 | Accepted: 2 October 2024 | Published: 2 October 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The progress in nanomedicine has sparked increasing concerns regarding its applications with biocompatible materials. Here, we assessed and optimized a three-dimensional (3D) bioprinting technique by testing various printing parameters with multiple cell types. Cell-laden scaffolds were designed, cultivated, imaged, and transplanted onto the dorsal skin of nude mice. The structure of bioprinted scaffolds retained its shape and dimensions with no cell migration between layers. Moreover, gold nanoparticles (GNPs) were intravenously administered to transplanted nude mice and aggregately deposited in the cell-laden scaffolds. Importantly, GNPs exhibited extensive accumulation in bioprinted scaffolds compared to natural skin and other organs in vivo. GNPs accumulated in the dermis of the transplanted scaffolds, while they stayed in the subcutaneous tissue of the natural skin with no permeation to the dermis, indicating a high absorption tendency of GNPs for artificial scaffolds. The results revealed a lack of similarity between the artificial skin scaffolds and natural skin, which may diminish their potential as artificial skin substitutes. Furthermore, the absorption property of 3D-bioprinted scaffolds suggests their potential as (i) a therapeutic method to absorb and excrete GNPs; and (ii) a strategy for targeted drug delivery of GNPs.  

Graphical abstract
Keywords
3D bioprinting
Skin scaffolds
Gold nanoparticles
Biodistribution
In vivo transplant
Funding
This work was supported by the STI2030-Major Projects (2022ZD0205202), the Anhui Province University Scientific Research Project (KJ2021A0212, 2022AH051169), the Anhui Medical University Research Funding (2021xkj008), the University Synergy Innovation Program of Anhui Province (GXXT-2022-030), and the College Students’ Innovation and Entrepreneurship Training Program of Anhui Province (S202210366019).
Conflict of interest
The authors declare no conflict of interest.
References
  1. Matai I, Kaur G, Seyedsalehi A, McClinton A, Laurencin CT. Progress in 3D bioprinting technology for tissue/ organ regenerative engineering. Biomaterials. 2020; 226:119536. doi: 10.1016/j.biomaterials.2019.119536
  2. Cubo N, Garcia M, Del Canizo JF, Velasco D, Jorcano JL. 3D bioprinting of functional human skin: production and in vivo analysis. Biofabrication. 2016;9(1):015006. doi: 10.1088/1758-5090/9/1/015006
  3. Zhu W, Ma X, Gou M, Mei D, Zhang K, Chen S. 3D printing of functional biomaterials for tissue engineering. Curr Opin Biotechnol. 2016;40:103-112. doi: 10.1016/j.copbio.2016.03.014
  4. Li X, Liu B, Pei B, et al. Inkjet bioprinting of biomaterials. Chem Rev. 2020;120(19):10793-10833. doi: 10.1021/acs.chemrev.0c00008
  5. Douillet C, Nicodeme M, Hermant L, et al. From local to global matrix organization by fibroblasts: a 4D laser-assisted bioprinting approach. Biofabrication. 2022;14(2):025006. doi: 10.1088/1758-5090/ac40ed
  6. Rossi A, Pescara T, Gambelli AM, et al. Biomaterials for extrusion-based bioprinting and biomedical applications. Front Bioeng Biotechnol. 2024;12:1393641. doi: 10.3389/fbioe.2024.1393641
  7. Li W, Wang M, Ma H, Chapa-Villarreal FA, Lobo AO, Zhang YS. Stereolithography apparatus and digital light processing-based 3D bioprinting for tissue fabrication. iScience. 2023;26(2):106039. doi: 10.1016/j.isci.2023.106039
  8. Weng T, Zhang W, Xia Y, et al. 3D bioprinting for skin tissue engineering: Current status and perspectives. J Tissue Eng. 2021;12:20417314211028574. doi: 10.1177/20417314211028574
  9. Rossi G, Manfrin A, Lutolf MP. Progress and potential in organoid research. Nat Rev Genet. 2018;19(11):671-687. doi: 10.1038/s41576-018-0051-9
  10. Hong ZX, Zhu ST, Li H, et al. Bioengineered skin organoids: from development to applications. Mil Med Res. 2023;10(1):40. doi: 10.1186/s40779-023-00475-7
  11. Zhao H, Chen Y, Shao L, et al. Airflow-assisted 3D bioprinting of human heterogeneous microspheroidal organoids with microfluidic nozzle. Small. 2018;14(39):e1802630. doi: 10.1002/smll.201802630
  12. Michael S, Sorg H, Peck CT, et al. Tissue engineered skin substitutes created by laser-assisted bioprinting form skin-like structures in the dorsal skin fold chamber in mice. PloS One. 2013;8(3):e57741. doi: 10.1371/journal.pone.0057741
  13. Chen Y, Feng X. Gold nanoparticles for skin drug delivery. Int J Pharm. 2022;625:122122. doi: 10.1016/j.ijpharm.2022.122122
  14. Revia RA, Stephen ZR, Zhang M. Theranostic nanoparticles for RNA-based cancer treatment. Acc Chem Res. 2019;52(6):1496-1506. doi: 10.1021/acs.accounts.9b00101
  15. de Puig H, Bosch I, Salcedo N, Collins JJ, Hamad-Schifferli K, Gehrke L. Multiplexed rapid antigen tests developed using multicolored nanoparticles and cross-reactive antibody pairs: implications for pandemic preparedness. Nano Today. 2022;47:101669. doi: 10.1016/j.nantod.2022.101669
  16. Surendran SP, Moon MJ, Park R, Jeong YY. Bioactive nanoparticles for cancer immunotherapy. Int J Mol Sci. 2018;19(12):3877. doi: 10.3390/ijms19123877
  17. Yang X, Yang J, Wang L, et al. Pharmaceutical intermediate-modified gold nanoparticles: against multidrug-resistant bacteria and wound-healing application via an electrospun scaffold. ACS Nano. 2017;11(6): 5737-5745. doi: 10.1021/acsnano.7b01240
  18. Randeria PS, Seeger MA, Wang XQ, et al. siRNA-based spherical nucleic acids reverse impaired wound healing in diabetic mice by ganglioside GM3 synthase knockdown. Proc Natl Acad Sci U S A. 2015;112(18):5573-5578. doi: 10.1073/pnas.1505951112
  19. Koushki K, Varasteh AR, Shahbaz SK, et al. Dc-specific aptamer decorated gold nanoparticles: a new attractive insight into the nanocarriers for allergy epicutaneous immunotherapy. Int J Pharm. 2020;584:119403. doi: 10.1016/j.ijpharm.2020.119403
  20. Niu J, Chu Y, Huang YF, et al. Transdermal gene delivery by functional peptide-conjugated cationic gold nanoparticle reverses the progression and metastasis of cutaneous melanoma. ACS Appl Mater Interfaces. 2017;9(11):9388-9401. doi: 10.1021/acsami.6b16378
  21. Kim HS, Sun X, Lee JH, Kim HW, Fu X, Leong KW. Advanced drug delivery systems and artificial skin grafts for skin wound healing. Adv Drug Deliv Rev. 2019;146:209-239. doi: 10.1016/j.addr.2018.12.014
  22. Wang XM, Wu XW, Zhao XY, Wang CW, Zhou JN. Exposure-time-dependent subcellular staging of gold nanoparticles deposition and vesicle destruction in mice livers. Nanomedicine. 2021;34:102393. doi: 10.1016/j.nano.2021.102393
  23. Lee V, Singh G, Trasatti JP, et al. Design and fabrication of human skin by three-dimensional bioprinting. Tissue Eng Part C Methods. 2014;20(6):473-484. doi: 10.1089/ten.TEC.2013.0335
  24. Lee W, Debasitis JC, Lee VK, et al. Multi-layered culture of human skin fibroblasts and keratinocytes through three-dimensional freeform fabrication. Biomaterials. 2009;30(8):1587-1595. doi: 10.1016/j.biomaterials.2008.12.009
  25. Tiwari R, Pathak K. Local drug delivery strategies towards wound healing. Pharmaceutics. 2023;15(2):634. doi: 10.3390/pharmaceutics15020634
  26. Osouli-Bostanabad K, Masalehdan T, Kapsa RMI, et al. Traction of 3D and 4D printing in the Healthcare Industry: from drug delivery and analysis to regenerative medicine. ACS Biomater Sci Eng. 2022;8(7):2764-2797. doi: 10.1021/acsbiomaterials.2c00094
  27. Sufiyan M, Kushwaha P, Ahmad M, Mandal P, Vishwakarma KK. Scaffold-mediated drug delivery for enhanced wound healing: a review. AAPS PharmSciTech. 2024;25(5):137. doi: 10.1208/s12249-024-02855-1
  28. Mbese Z, Alven S, Aderibigbe BA. Collagen-based nanofibers for skin regeneration and wound dressing applications. Polymers (Basel). 2021;13(24):4368. doi: 10.3390/polym13244368
  29. Liang Y, He J, Guo B. Functional hydrogels as wound dressing to enhance wound healing. ACS Nano. 2021;15(8):12687-12722. doi: 10.1021/acsnano.1c04206
  30. An B, Lin YS, Brodsky B. Collagen interactions: drug design and delivery. Adv Drug Deliv Rev. 2016;97:69-84. doi: 10.1016/j.addr.2015.11.013
  31. Yanez M, Rincon J, Dones A, De Maria C, Gonzales R, Boland T. In vivo assessment of printed microvasculature in a bilayer skin graft to treat full-thickness wounds. Tissue Eng Part A. 2015;21(1-2):224-233. doi: 10.1089/ten.TEA.2013.0561
  32. Eweida AM, Marei MK. Naturally occurring extracellular matrix scaffolds for dermal regeneration: do they really need cells? Biomed Res Int. 2015;2015:839694. doi: 10.1155/2015/839694
  33. Lee CH, Singla A, Lee Y. Biomedical applications of collagen. Int J Pharm. 2001;221(1-2):1-22. doi: 10.1016/s0378-5173(01)00691-3
  34. Kang MS, Lee SY, Kim KS, Han DW. State of the art biocompatible gold nanoparticles for cancer theragnosis. Pharmaceutics. 2020;12(8):701. doi: 10.3390/pharmaceutics12080701
  35. Akshaya K, Arthi C, Pavithra AJ, et al. Bioconjugated gold nanoparticles as an efficient colorimetric sensor for cancer diagnostics. Photodiagnosis Photodyn Ther. 2020;30:101699. doi: 10.1016/j.pdpdt.2020.101699
  36. Hahn MA, Singh AK, Sharma P, Brown SC, Moudgil BM. Nanoparticles as contrast agents for in-vivo bioimaging: current status and future perspectives. Anal Bioanal Chem. 2011;399(1):3-27. doi: 10.1007/s00216-010-4207-5
  37. Oliveira BB, Ferreira D, Fernandes AR, Baptista PV. Engineering gold nanoparticles for molecular diagnostics and biosensing. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2023;15(1):e1836. doi: 10.1002/wnan.1836
  38. Comune M, Rai A, Chereddy KK, et al. Antimicrobial peptide-gold nanoscale therapeutic formulation with high skin regenerative potential. J Control Release. 2017;262:58-71. doi: 10.1016/j.jconrel.2017.07.007
  39. Cao M, Li B, Guo M, et al. In vivo percutaneous permeation of gold nanomaterials in consumer cosmetics: implication in dermal safety assessment of consumer nanoproducts. Nanotoxicology. 2021;15(1):131-144. doi: 10.1080/17435390.2020.1860264
  40. Huang Y, Yu F, Park YS, et al. Co-administration of protein drugs with gold nanoparticles to enable percutaneous delivery. Biomaterials. 2010;31(34):9086-9091. doi: 10.1016/j.biomaterials.2010.08.046
  41. Mascarenhas-Melo F, Mathur A, Murugappan S, et al. Inorganic nanoparticles in dermopharmaceutical and cosmetic products: properties, formulation development, toxicity, and regulatory issues. Eur J Pharm Biopharm. 2023;192:25-40. doi: 10.1016/j.ejpb.2023.09.011
  42. Labouta HI, Liu DC, Lin LL, et al. Gold nanoparticle penetration and reduced metabolism in human skin by toluene. Pharm Res. 2011;28(11):2931-2944. doi: 10.1007/s11095-011-0561-z
  43. Wilson CG, Sisco PN, Gadala-Maria FA, Murphy CJ, Goldsmith EC. Polyelectrolyte-coated gold nanorods and their interactions with type I collagen. Biomaterials. 2009;30(29):5639-5648. doi: 10.1016/j.biomaterials.2009.07.011
  44. Slowinska K. Cross-linked collagen gels using gold nanoparticles. Methods Mol Biol. 2018;1798:203-212. doi: 10.1007/978-1-4939-7893-9_16
  45. Schuetz T, Richmond N, Harmon ME, Schuetz J, Castaneda L, Slowinska K. The microstructure of collagen type I gel cross-linked with gold nanoparticles. Colloids Surf B Biointerfaces. 2013;101:118-125. doi: 10.1016/j.colsurfb.2012.06.006
  46. Akturk O, Kismet K, Yasti AC, et al. Collagen/gold nanoparticle nanocomposites: a potential skin wound healing biomaterial. J Biomater Appl. 2016;31(2):283-301. doi: 10.1177/0885328216644536
  47. Sasidharan S, Pottail L. Biodegradable polymers and gold nanoparticle-decorated skin substitutes: synthesis, characterization, and in vitro biological activities. Appl Biochem Biotechnol. 2021;193(10):3232-3252. doi: 10.1007/s12010-021-03600-1
  48. Khlebtsov N, Dykman L. Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. Chem Soc Rev. 2011;40(3):1647-1671. doi: 10.1039/c0cs00018c
  49. Sykes EA, Dai Q, Tsoi KM, Hwang DM, Chan WC. Nanoparticle exposure in animals can be visualized in the skin and analysed via skin biopsy. Nat Commun. 2014;5:3796. doi: 10.1038/ncomms4796
  50. Mortensen LJ, Oberdörster G, Pentland AP, DeLouise LA. In vivo skin penetration of quantum dot nanoparticles in the murine model: the effect of UVR. Nano Lett. 2008;8(9):2779-2787. doi: 10.1021/nl801323y
  51. Smith LT, Holbrook KA, Byers PH. Structure of the dermal matrix during development and in the adult. J Invest Dermatol. 1982;79(Suppl 1):93s-104s. doi: 10.1111/1523-1747.ep12545877
  52. Zidek J, Vojtova L, Abdel-Mohsen AM, et al. Accurate micro-computed tomography imaging of pore spaces in collagen-based scaffold. J Mater Sci Mater Med. 2016;27(6):110. doi: 10.1007/s10856-016-5717-2
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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