Advancements in Human Skin Models: From Basic Constructs to Disease-Specific Platforms for Drug Discovery and Therapeutics
Keywords:
in-vitro skin modelling, diseased human skin, bio fabrication techniques, skin engineeringAbstract
Skin serves as a major barrier to protect the body from physical, chemical, and pathological risks as well as adjust the transportation of two-way ions and nutrients. To improve the structure and function of skin as well as skin diseases, animal experience is often used, but the difference between surgery and physiology can cause poor animal data in clinical situations. In vitro, models such as the rebuilt epidermis of humans or the equivalent skin are valuable alternatives for animal experiments. There is now a greater demand for alternative in vitro platforms that replicate the structural and functional characteristics of natural skin due to ethical issues and genetic variations in traditional animal investigations. In vitro skin modelling has advanced significantly in recent decades; however, to replicate the pathological characteristics of diseased human skin, distinct repeatable bio-fabrication techniques are needed in comparison to those employed for healthy-skin models, the structural and functional features of healthy human skin to explain human skin modelling with disease markers. detail on how to replicate diseased human skin models in vitro, such as models for atopic, diabetic, skin-cancer, injured, and other pathological skin types. an outlook on diseased‑skin modelling and its technical perspective for the further development of skin engineering.
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Moniz, T., Costa Lima, S. A., & Reis, S. (2020). Human skin models: From healthy to disease‐mimetic systems; characteristics and applications. British Journal of Pharmacology, 177(19), 4314–4329. https://doi.org/10.1111/bph.15184
Cai, R., Gimenez-Camino, N., Xiao, M., Bi, S., & DiVito, K. A. (2023). Technological advances in three-dimensional skin tissue engineering. Reviews on Advanced Materials Science, 62, Article 20220289. https://doi.org/10.1515/rams-2022-0289
Risueño, I., Valencia, L., Jorcano, J. L., & Velasco, D. (2021). Skin-on-a-chip models: General overview and future perspectives. APL Bioengineering, 5(3), 030901. https://doi.org/10.1063/5.0046376
Hofmann, E., Schwarz, A., Fink, J., Kamolz, L.-P., & Kotzbeck, P. (2023). Modelling the complexity of human skin in vitro . Biomedicines, 11(3), 794. https://doi.org/10.3390/biomedicines11030794
Derr, K., Zou, J., Luo, K., Song, M. J., Sittampalam, G. S., Zhou, C., Michael, S., Ferrer, M., & Derr, P. (2019). Fully three-dimensional bioprinted skin equivalent constructs with validated morphology and barrier function. Tissue Engineering Part C: Methods, 25(6), 334–343. https://doi.org/10.1089/ten.tec.2018.0318
Bajsert, J., De Glas, V., Faway, E., Lambert de Rouvroit, C., Pérez-Aso, M., Cook, P. W., & Poumay, Y. (2024). Characterization of reconstructed human epidermis in a chemically-defined, animal origin-free cell culture. JID Innovations, 4, 100298. https://doi.org/10.1016/j.xjidi.2024.100298
Ahn, M., Cho, W.-W., Park, W., Lee, J.-S., Choi, M.-J., Gao, Q., Gao, G., Cho, D.-W., & Kim, B. S. (2023). 3D biofabrication of diseased human skin models in vitro . Biomaterials Research, 27(80). https://doi.org/10.1186/s40824-023-00415-5
Lee, V., Singh, G., Trasatti, J. P., Bjornsson, C., Xu, X., Tran, T. N., Yoo, S.-S., Dai, G., & Karande, P. (2014). Design and fabrication of human skin by three-dimensional bioprinting. Tissue Engineering: Part C, 20(6), 473–484. https://doi.org/10.1089/ten.tec.2013.0335
Avci, P.; Sadasivam, M.; Gupta, A.; Melo, W.; Huang, Y.-Y.; Yin, R.; Chandran, R.; Kumar, R.; Otufowora, A.; Nyame, T.; et al. Animal models of skin disease for drug discovery. Expert Opin. Drug Discov. 2013, 8, 331–355. [CrossRef]
Jung, E.C.; Maibach, H.I. Animal models for percutaneous absorption. J. Appl. Toxicol. 2015, 35, 1–10. [CrossRef] Dellambra, E.; Odorisio, T.; D’Arcangelo, D.; Failla, C.M.; Facchiano, A. Non-animal models in dermatological research. ALTEX 2019, 36, 177–202. [CrossRef]
Santoro, M., Navarro, J., and Fisher, J.P. Micro- and macrobioprinting: current trends in tissue modeling and organ fabrication. Small Methods 1700318, 1, 2018.
Ma, X., Liu, J., Zhu, W., et al. 3D bioprinting of functional tissue models for personalized drug screening and in vitro disease modeling. Adv Drug Deliv Rev 132, 235, 2018.
Bouwstra, J.A. The skin barrier, a well-organized mem brane. Colloids Surfaces 124, 403, 1997.
Ahn M, Cho WW, Kim BS, Cho DW. Engineering densely packed adipose tissue via environmentally controlled in bath 3D sioprinting. Adv Funct Mater. 2022;32(28):2200203.
Lee MC, Lee WJ, Lee BI, Chung KY, Kim JW, Kang EH, Kim YO. Adipose tis sue formation utilizing fat flap distraction technique. Sci Rep. 2017;7:1–10.
Maniţă, P. G., I. García-Orue, E. Santos-Vizcaíno, R. M. Hernandez, and M. Igartua. 3D bioprinting of functional skin substitutes for chronic wound treatment: from current achievements to future goals. Pharmaceuticals, Vol. 14, 2021, id. 362.
Randall, M. J., Jüngel, A., Rimann, M., & Wuertz-Kozak, K. (2018). Advances in the biofabrication of 3D skin in vitro : Healthy and pathological models. Frontiers in Bioengineering and Biotechnology, 6, Article 154. https://doi.org/10.3389/fbioe.2018.001540
W. D. James, T. G. Berger, and D. M. Elston, Andrews’ Diseases of the Skin: Clinical Dermatology (Elsevier, 2015), p. 12e.
Imran, M., Moyle, P. M., Kamato, D., & Mohammed, Y. (2024). Advances in, and prospects of, 3D preclinical models for skin drug discovery. Drug Discovery Today, 29(12), 104208. https://doi.org/10.1016/j.drudis.2024.104208
Meyer, W., Schonnagel, B., & Fleischer, L. G. (2006). A note on integumental (1→3)(1→6)-β-D-glucan permeation, using the porcine ear skin model. Journal of Cosmetic Dermatology, 5(2), 130–134. https://doi.org/10.1111/j.1473-2165.2006.00240.x
Schreiber, S., Mahmoud, A., Vuia, A., Rubbelke, M. K., Schmidt, E., Schaller, M., … Schäfer-Korting, M. (2005). Reconstructed epidermis versus human and animal skin in skin absorption studies. Toxicology in vitro , 19(6), 813–822. https://doi.org/10.1016/j.tiv.2005.06.008
Ternullo, S., Basnet, P., Holsæter, A. M., Flaten, G. E., de Weerd, L., & Škalko-Basnet, N. (2018). Deformable liposomes for skin therapy with human epidermal growth factor: The effect of liposomal surface charge. European Journal of Pharmaceutical Sciences, 125, 163–171. https://doi.org/10.1016/j.ejps.2018.09.001
Zhang, Q., Sito, L., Mao, M., He, J., Zhang, Y. S., & Zhao, X. (2018). Current advances in skin-on-a-chip models for drug testing. Microphysiological Systems, 2, Article 2. https://doi.org/10.21037/mps.2018.08.02
O’Neill, A. T., Monteiro-Riviere, N. A., & Walker, G. M. (2008). Characterization of microfluidic human epidermal keratinocyte culture. Cytotechnology, 56(3), 197–207. https://doi.org/10.1007/s10616-008-9141-3
Kieninger, J., Weltin, A., Flamm, H., & Urban, G. A. (2018). Microsensor systems for cell metabolism—from 2D culture to organ-on-chip. Lab on a Chip, 18(9), 1274–1291. https://doi.org/10.1039/C8LC00010J
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