Skip to main content

Advertisement

Log in

Decision matrix for integrating 3D printing technologies for biomanufacturing of alternative testing model

  • ORIGINAL ARTICLE
  • Published:
The International Journal of Advanced Manufacturing Technology Aims and scope Submit manuscript

Abstract

The ethical concerns surrounding the use of animals in cosmetics testing have spurred the demand for alternative test models. Digital manufacturing, often denoted as 3D printing, presents a compelling and cost-effective avenue for fabricating such testing models. The current manuscript proposes a digitally manufactured alternative testing platform that comprises three main components: bioprinted skin model, platform fabrication and electronic printing. For the first time, we assessed bioprinted skin models for the intention for use in cosmetic testing. We employed OECD guidelines to test on the skin model’s responsiveness to anti-ageing products and irritant compounds. Our studies showed the efficacy of our bioprinted skin model capable of evaluating cosmetic compounds. An evaluation matrix was used to select the appropriate digital manufacturing technology to fabricate the setup for alternative testing model. Multi-material jetting was selected as the most appropriate additive manufacturing technology to introduce modularity and water-tight designs for the test platform. We have also introduced an electronic component in the test platform fabricated using electronic printing to provide localised heating on the skin model. Overall, this study highlights the potential of digital manufacturing and biomanufacturing to promote ethical and sustainable practices in cosmetic testing. Moreover, the decision matrix showcase in this study will be beneficial for scientists and researchers in application-driven selection on 3D printing technology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Ferreira M, Matos A, Couras A, Marto J, Ribeiro H (2022) Overview of cosmetic regulatory frameworks around the world. Cosmetics 9(4):72. https://doi.org/10.3390/cosmetics9040072

    Article  Google Scholar 

  2. Gagosian V et al (2022) The potential use of kraft lignins as natural ingredients for cosmetics: evaluating their photoprotective activity and skin irritation potential. Int J Biol Macromol 222:2535–2544. https://doi.org/10.1016/j.ijbiomac.2022.10.037

    Article  Google Scholar 

  3. Silva R, Tamburic S (2022) A state-of-the-art review on the alternatives to animal testing for the safety assessment of cosmetics. Cosmetics 9(5). https://doi.org/10.3390/cosmetics9050090

  4. Fox S, Polak J, Schmid Daners M, Meboldt M (2019) Fabrication of bioengineered skin by injection molding: a feasibility study on automation. SLAS Technol 24(5):506–514. https://doi.org/10.1177/2472630319857966

    Article  Google Scholar 

  5. Derr K et al (2019) Fully three-dimensional bioprinted skin equivalent constructs with validated morphology and barrier function. Tissue Eng Part C Methods 25(6):334–343. https://doi.org/10.1089/ten.tec.2018.0318

    Article  Google Scholar 

  6. Madiedo-Podvrsan S et al (2021) Utilization of patterned bioprinting for heterogeneous and physiologically representative reconstructed epidermal skin models. Sci Rep 11(1):6217. https://doi.org/10.1038/s41598-021-85553-3

    Article  Google Scholar 

  7. Lee H-R, Park JA, Kim S, Jo Y, Kang D, Jung S (2021) 3D microextrusion-inkjet hybrid printing of structured human skin equivalents. Bioprinting 22:e00143. https://doi.org/10.1016/j.bprint.2021.e00143

    Article  Google Scholar 

  8. Kim BS, Gao G, Kim JY, Cho D (2019) 3D cell printing of perfusable vascularized human skin equivalent composed of epidermis, dermis, and hypodermis for better structural recapitulation of native skin. Adv Healthc Mater 8(7):1801019. https://doi.org/10.1002/adhm.201801019

    Article  Google Scholar 

  9. Ng WL, Qi JTZ, Yeong WY, Naing MW (2018) Proof-of-concept: 3D bioprinting of pigmented human skin constructs. Biofabrication 10(2):025005. https://doi.org/10.1088/1758-5090/aa9e1e

    Article  Google Scholar 

  10. Liu X, Michael S, Bharti K, Ferrer M, Song M (2020) A biofabricated vascularized skin model of atopic dermatitis for preclinical studies. Biofabrication 12(3). https://doi.org/10.1088/1758-5090/ab76a1

  11. Mehta P et al (2019) Engineering optimisation of commercial facemask formulations capable of improving skin moisturisation. Int J Cosmet Sci 41(5):462–471. https://doi.org/10.1111/ics.12560

    Article  Google Scholar 

  12. Gore E, Picard C, Savary G (2020) Complementary approaches to understand the spreading behavior on skin of O/W emulsions containing different emollientss. Colloids Surf B Biointerfaces 193. https://doi.org/10.1016/j.colsurfb.2020.111132

  13. Yusof NZ, Abd Gani SS, Azizul Hasan ZA, Idris Z (2018) Skin and eye irritation assessment of oil palm (Elaeis guineensis) leaf extract for topical application. Int J Toxicol 37(4):335–343. https://doi.org/10.1177/1091581818773979

    Article  Google Scholar 

  14. Kose O, Erkekoglu P, Sabuncuoglu S, Kocer-Gumusel B (2018) Evaluation of skin irritation potentials of different cosmetic products in Turkish market by reconstructed human epidermis model. Regul Toxicol Pharmacol 98:268–273. https://doi.org/10.1016/j.yrtph.2018.08.010

    Article  Google Scholar 

  15. Han J et al (2020) Me-too validation study for in vitro skin irritation test with a reconstructed human epidermis model, KeraSkinTM for OECD test guideline 439. Regul Toxicol Pharmacol 117:104725. https://doi.org/10.1016/j.yrtph.2020.104725

    Article  Google Scholar 

  16. Salas T, Bordes C, Arquier D, Caillier L, Mandica F, Bolzinger M-A (2023) Effect of massage on retinol skin penetration. Int J Pharm 642:123106. https://doi.org/10.1016/j.ijpharm.2023.123106

    Article  Google Scholar 

  17. Szczepańska E et al (2020) Synthesis of silver nanoparticles in context of their cytotoxicity, antibacterial activities, skin penetration and application in skincare products. Supramol Chem 32(3):207–221. https://doi.org/10.1080/10610278.2020.1726917

    Article  Google Scholar 

  18. Naderi A, Bhattacharjee N, Folch A (2019) Digital manufacturing for microfluidics. Annu Rev Biomed Eng 21(1):325–364. https://doi.org/10.1146/annurev-bioeng-092618-020341

    Article  Google Scholar 

  19. Au AK, Lee W, Folch A (2014) Mail-order microfluidics: evaluation of stereolithography for the production of microfluidic devices. Lab Chip 14(7):1294–1301. https://doi.org/10.1039/C3LC51360B

    Article  Google Scholar 

  20. Shallan AI, Smejkal P, Corban M, Guijt RM, Breadmore MC (2014) Cost-effective three-dimensional printing of visibly transparent microchips within minutes. Anal Chem 86(6):3124–3130. https://doi.org/10.1021/ac4041857

    Article  Google Scholar 

  21. Zhao S, Cong H, Pan T (2009) Direct projection on dry-film photoresist (DP 2): do-it-yourself three-dimensional polymer microfluidics. Lab Chip 9(8):1128–1132

    Article  Google Scholar 

  22. Anderson JR et al (2000) Fabrication of topologically complex three-dimensional microfluidic systems in PDMS by rapid prototyping. Anal Chem 72(14):3158–3164

    Article  Google Scholar 

  23. Liao Y et al (2012) Rapid prototyping of three-dimensional microfluidic mixers in glass by femtosecond laser direct writing. Lab Chip 12(4):746–749

    Article  Google Scholar 

  24. Lee JM, Zhang M, Yeong WY (2016) Characterization and evaluation of 3D printed microfluidic chip for cell processing. Microfluid Nanofluidics 20(1):5

    Article  Google Scholar 

  25. Cui H, Zhu W, Holmes B, Zhang LG (2016) Biologically inspired smart release system based on 3D bioprinted perfused scaffold for vascularized tissue regeneration. Adv Sci 3(8):1600058. https://doi.org/10.1002/advs.201600058

    Article  Google Scholar 

  26. Yen HJ, Tseng CS, Hsu SH, Tsai CL (2009) Evaluation of chondrocyte growth in the highly porous scaffolds made by fused deposition manufacturing (FDM) filled with type II collagen. Biomed Microdevices 11(3):615–624. https://doi.org/10.1007/s10544-008-9271-7

    Article  Google Scholar 

  27. Ramanath HS, Chua CK, Leong KF, Shah KD (2008) Melt flow behaviour of poly-epsilon-caprolactone in fused deposition modelling. J Mater Sci Mater Med 19(7):2541–2550. https://doi.org/10.1007/s10856-007-3203-6

    Article  Google Scholar 

  28. Jaidev LR, Chatterjee K (2019) Surface functionalization of 3D printed polymer scaffolds to augment stem cell response. Mater Des 161:44–54. https://doi.org/10.1016/j.matdes.2018.11.018

    Article  Google Scholar 

  29. Kjar A, Huang Y (2019) Application of micro-scale 3D printing in pharmaceutics. Pharmaceutics 11(8):390

    Article  Google Scholar 

  30. Jiao C et al (2020) Preparation of Al2O3-ZrO2 scaffolds with controllable multi-level pores via digital light processing. J Eur Ceram Soc 40(15):6087–6094

    Article  Google Scholar 

  31. Samson KD, Hidalgo-Alvarez V, Dargaville TR, Melchels FP (2023) Tough, resorbable polycaprolactone-based bimodal networks for vat polymerization 3D printing. Adv Funct Mater 33(25):2213797. https://doi.org/10.1002/adfm.202213797

    Article  Google Scholar 

  32. Taylor AP, Velásquez–García LF (2019) Low-cost, monolithically 3D-printed, miniature high-flow rate liquid pump. J Phys Conf Ser 1407(1):012040. https://doi.org/10.1088/1742-6596/1407/1/012040

    Article  Google Scholar 

  33. Beckwith AL, Borenstein JT, Velásquez-García LF (2018) Monolithic, 3D-printed microfluidic platform for recapitulation of dynamic tumor microenvironments. J Microelectromech Syst 27(6):1009–1022. https://doi.org/10.1109/JMEMS.2018.2869327

    Article  Google Scholar 

  34. Su R et al (2020) 3D printed self-supporting elastomeric structures for multifunctional microfluidics. Sci Adv 6(41):eabc9846. https://doi.org/10.1126/sciadv.abc9846

    Article  Google Scholar 

  35. Waheed S et al (2016) 3D printed microfluidic devices: enablers and barriers. Lab Chip 16(11):1993–2013. https://doi.org/10.1039/C6LC00284F

    Article  Google Scholar 

  36. Lee JM, Yeong WY (2020) Engineering macroscale cell alignment through coordinated toolpath design using support-assisted 3D bioprinting. J R Soc Interface 17(168). https://doi.org/10.1098/rsif.2020.0294

  37. Lee A et al (2019) 3D bioprinting of collagen to rebuild components of the human heart. Science 365(6452):482–487. https://doi.org/10.1126/science.aav9051

    Article  Google Scholar 

  38. Lee JM, Yeong WY (2016) Design and printing strategies in 3D bioprinting of cell-hydrogels: a review. Adv Healthc Mater 5(22):2856–2865

    Article  Google Scholar 

  39. Zhang YS et al (2021) 3D extrusion bioprinting. Nat Rev Methods Primers 1(1):75. https://doi.org/10.1038/s43586-021-00073-8

    Article  Google Scholar 

  40. Campbell A et al (2021) Novel Combinatorial strategy using thermal inkjet bioprinting, chemotherapy, and radiation on human breast cancer cells; an in-vitro cell viability assessment. Materials 14(24):7864. https://doi.org/10.3390/ma14247864

    Article  Google Scholar 

  41. Wang Q et al (2023) A study on cell viability based on thermal inkjet three-dimensional bioprinting. Phys Fluids 35(8):082007. https://doi.org/10.1063/5.0159135

    Article  Google Scholar 

  42. Lee HJ et al (2015) A new approach for fabricating collagen/ECM-based bioinks using preosteoblasts and human adipose stem cells. Adv Healthc Mater 4(9):1359–1368. https://doi.org/10.1002/adhm.201500193

    Article  Google Scholar 

  43. Diamantides N et al (2017) Correlating rheological properties and printability of collagen bioinks: the effects of riboflavin photocrosslinking and pH. Biofabrication 9(3):034102. https://doi.org/10.1088/1758-5090/aa780f

    Article  Google Scholar 

  44. Cavallo A et al (2023) Marine collagen-based bioink for 3D bioprinting of a bilayered skin model. Pharmaceutics 15(5):1331. https://doi.org/10.3390/pharmaceutics15051331

    Article  Google Scholar 

  45. Ghosh S, Blankschtein D (2008) The role of sodium dodecyl sulfate (SDS) micelles in inducing skin barrier perturbation in the presence of glycerol. Int J Cosmet Sci 30(1):73–73. https://doi.org/10.1111/j.1468-2494.2007.00401_1.x

    Article  Google Scholar 

  46. Wei Z et al (2020) Two-dimensional cellular and three-dimensional bio-printed skin models to screen topical-use compounds for irritation potential. Front Bioeng Biotechnol 8:109. https://doi.org/10.3389/fbioe.2020.00109

    Article  Google Scholar 

  47. Ravetti S, Clemente C, Brignone S, Hergert L, Allemandi D, Palma S (2019) Ascorbic acid in skin health. Cosmetics 6(4). https://doi.org/10.3390/cosmetics6040058

  48. Ben Hsouna A et al (2023) The chemical variability, nutraceutical value, and food-industry and cosmetic applications of citrus plants: a critical review. Antioxidants 12(2). https://doi.org/10.3390/antiox12020481

  49. Liping L, Kexin L, Huipu D, Jia L, Jie Z (2020) Study on preparation of a chitosan/vitamin c complex and its properties in cosmetics. Nat Prod Commun 15(10). https://doi.org/10.1177/1934578X20946876

  50. Jarząbek-Perz S, Dziedzic M, Rotsztejn H, Kołodziejczak A (2023) Evaluation of the effects of 10% and 30% gluconolactone chemical peel on sebum, pH, and TEWL. J Cosmet Dermatol. https://doi.org/10.1111/jocd.15864

  51. Chojkier M, Houglum K, Solis-Herruzo J, Brenner DA (1989) Stimulation of collagen gene expression by ascorbic acid in cultured human fibroblasts. J Biol Chem 264(28):16957–16962. https://doi.org/10.1016/S0021-9258(19)84800-7

    Article  Google Scholar 

  52. Kishimoto Y, Saito N, Kurita K, Shimokado K, Maruyama N, Ishigami A (2013) Ascorbic acid enhances the expression of type 1 and type 4 collagen and SVCT2 in cultured human skin fibroblasts. Biochem Biophys Res Commun 430(2):579–584. https://doi.org/10.1016/j.bbrc.2012.11.110

    Article  Google Scholar 

  53. Boo YC (2022) Ascorbic acid (vitamin C) as a cosmeceutical to increase dermal collagen for skin antiaging purposes: emerging combination therapies. Antioxidants 11(9). https://doi.org/10.3390/antiox11091663

  54. D’Aniello C, Cermola F, Patriarca EJ, Minchiotti G (2017) Vitamin C in stem cell biology: impact on extracellular matrix homeostasis and epigenetics. Stem Cells Int 2017:1–16. https://doi.org/10.1155/2017/8936156

    Article  Google Scholar 

  55. Tajima S, Pinnell SR (1996) Ascorbic acid preferentially enhances type I and III collagen gene transcription in human skin fibroblasts. J Dermatol Sci 11(3):250–253. https://doi.org/10.1016/0923-1811(95)00640-0

    Article  Google Scholar 

  56. Hachem J-P et al (2010) Acute acidification of stratum corneum membrane domains using polyhydroxyl acids improves lipid processing and inhibits degradation of corneodesmosomes. J Invest Dermatol 130(2):500–510. https://doi.org/10.1038/jid.2009.249

    Article  Google Scholar 

  57. Bernstein EF, Brown DB, Schwartz MD, Kaidbey K, Ksenzenko SM (2004) The polyhydroxy acid gluconolactone protects against ultraviolet radiation in an in vitro model of cutaneous photoaging. Dermatol Surg 30(2):189–196. https://doi.org/10.1111/j.1524-4725.2004.30060.x

    Article  Google Scholar 

  58. Zerbinati N et al (2023) Investigation on the biological safety and activity of a gluconolactone-based lotion for dermocosmetic application. Pharmaceuticals 16(5). https://doi.org/10.3390/ph16050655

  59. Salamanca CH, Barrera-Ocampo A, Lasso JC, Camacho N, Yarce CJ (2018) Franz Diffusion cell approach for pre-formulation characterisation of ketoprofen semi-solid dosage forms. Pharmaceutics 10(3). https://doi.org/10.3390/pharmaceutics10030148

  60. Pulsoni I et al (2022) Comparison between franz diffusion cell and a novel micro-physiological system for in vitro penetration assay using different skin models. SLAS Technol 27(3):161–171. https://doi.org/10.1016/j.slast.2021.12.006

    Article  Google Scholar 

  61. Pellevoisin C et al (2018) SkinEthicTM RHE for in vitro evaluation of skin irritation of medical device extracts. Toxicol In Vitro 50:418–425. https://doi.org/10.1016/j.tiv.2018.01.008

    Article  Google Scholar 

  62. Tsai P-C, Zhang Z, Florek C, Michniak-Kohn BB (2016) Constructing human skin equivalents on porcine acellular peritoneum extracellular matrix for in vitro irritation testing. Tissue Eng Part A 22(1–2):111–122. https://doi.org/10.1089/ten.tea.2015.0209

    Article  Google Scholar 

  63. Naito C et al (2021) Human induced pluripotent stem cell-based skin for assessing transdermal drug permeability and irritancy. Biol Pharm Bull 44(1):140–143. https://doi.org/10.1248/bpb.b20-00587

    Article  Google Scholar 

  64. Xiao J, Yang D, Li Q, Tian W, Guo W (2018) The establishment of a chemically defined serum-free culture system for human dental pulp stem cells. Stem Cell Res Ther 9(1):191. https://doi.org/10.1186/s13287-018-0928-8

    Article  Google Scholar 

  65. Van Der Valk J et al (2010) Optimization of chemically defined cell culture media – replacing fetal bovine serum in mammalian in vitro methods. Toxicol In Vitro 24(4):1053–1063. https://doi.org/10.1016/j.tiv.2010.03.016

    Article  Google Scholar 

  66. Suwannasom N, Kao I, Pruß A, Georgieva R, Bäumler H (2020) Riboflavin: the health benefits of a forgotten natural vitamin. IJMS 21(3):950. https://doi.org/10.3390/ijms21030950

    Article  Google Scholar 

  67. Maisch T et al (2014) Fast and effective photodynamic inactivation of multiresistant bacteria by cationic riboflavin derivatives. PloS One 9(12):e111792. https://doi.org/10.1371/journal.pone.0111792

    Article  Google Scholar 

  68. Xiao Q et al (2018) Discovery and development of natural products and their derivatives as photosensitizers for photodynamic therapy. CMC 25(7):839–860. https://doi.org/10.2174/0929867324666170823143137

    Article  Google Scholar 

  69. Wangsuwan S, Meephansan J (2019) Comparative study of photodynamic therapy with riboflavin-tryptophan gel and 13% 5-aminolevulinic acid in the treatment of mild to moderate acne vulgaris. CCID 12:805–814. https://doi.org/10.2147/CCID.S227737

    Article  Google Scholar 

  70. Agarwala S, Lee JM, Ng WL, Layani M, Yeong WY, Magdassi S (2018) A novel 3D bioprinted flexible and biocompatible hydrogel bioelectronic platform. Biosens Bioelectron 102:365–371. https://doi.org/10.1016/j.bios.2017.11.039

    Article  Google Scholar 

  71. Nair M, Best SM, Cameron RE (2020) Crosslinking collagen constructs: achieving cellular selectivity through modifications of physical and chemical properties. Appl Sci 10(19):6911

    Article  Google Scholar 

  72. Jagušić M et al (2016) Stability of minimum essential medium functionality despite L-glutamine decomposition. Cytotechnology 68(4):1171–1183. https://doi.org/10.1007/s10616-015-9875-8

    Article  Google Scholar 

  73. Yao T, Asayama Y (2017) Animal-cell culture media: history, characteristics, and current issues. Reprod Med Biol 16(2):99–117. https://doi.org/10.1002/rmb2.12024

    Article  Google Scholar 

  74. Arii K, Kobayashi H, Kai T, Kokuba Y (1999) Degradation kinetics of l-glutamine in aqueous solution. Eur J Pharm Sci 9(1):75–78. https://doi.org/10.1016/S0928-0987(99)00047-0

    Article  Google Scholar 

Download references

Funding

This research is supported by NAMIC Singapore and funded by the National Research Foundation Singapore under its Innovation Cluster Programme. This work is also supported by the Singapore Centre for 3D Printing, Nanyang Technological University, Singapore, through the use of its additive manufacturing facilities. Funding awardee: Wai Yee Yeong.

Author information

Authors and Affiliations

Authors

Contributions

J. M. Lee and W. Y. Yeong conceived the presented idea. J. M. Lee and M. J. Tan planned and conducted the in vitro bioprinted skin model experiments. M. J. Tan designed the culturing protocol for bioprinted skin model. J. M. Lee designed the CAD model, manufactured the ISD and evaluated its efficacy in the diffusion study. W. C. Ma fabricated and conducted the experiments on electronic printing of heating coils. W. Y. Yeong supervised the project.

Corresponding author

Correspondence to Jia Min Lee.

Ethics declarations

The authors declare no competing interests.

Disclaimer

Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not reflect the views of National Research Foundation, Singapore and NAMIC Singapore.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(DOCX 3923 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, J.M., Tan, M.J., Ma, W.C. et al. Decision matrix for integrating 3D printing technologies for biomanufacturing of alternative testing model. Int J Adv Manuf Technol 130, 4137–4149 (2024). https://doi.org/10.1007/s00170-024-12966-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00170-024-12966-5

Keywords

Navigation