AccScience Publishing / OR / Online First / DOI: 10.36922/OR026200025
Submit to OR
Cite this article
68
Views
Related Info Links
Google Scholar
More by Authors Links
Bin Shu
Suiqing Huang
Junyou Zhu
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ARTICLE

Construction strategies of skin organoids: A review

Miao Zhen1† ,  Tianjiao Li2† ,  Tongxin Chu1† ,  Shiyu Li3 ,  Zhenning Dai4 ,  Jian Hou5 ,  Peng Lei6 ,  Julin Xie1 ,  Bin Shu1* ,  Suiqing Huang7* ,  Junyou Zhu1*
Show Less
1 Department of Burns and Wound Repair, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
2 Experimental Center for Preventive Medicine, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
3 Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, Guangdong, China
4 Department of Stomatology, Guangdong Provincial Key Laboratory of Research and Development in Traditional Medicine, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou, Guangdong, China
5 Department of Cardiology, Cardiovascular Research Institute, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
6 Department of Surgery, Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, Massachusetts, United States of America
7 Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
†These authors contributed equally to this work.
OR, 026200025 https://doi.org/10.36922/OR026200025
Received: 13 May 2026 | Revised: 11 June 2026 | Accepted: 24 June 2026 | Published online: 14 July 2026
© 2026 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/ )
Download PDF
XML
Cite
Abstract

Skin organoids have evolved into versatile models, including reconstructed epidermis, skin equivalents, and composite organoids with appendages. Despite this progress, a unified framework linking construction approaches with developmental outcomes and experimental value remains needed. This review summarizes key determinants of organoid construction: cell source, assembly methods, extracellular matrix, precise signaling control, and quality assessment. It addresses how these factors shape developmental complexity, reproducibility, and scalability, guiding model selection. Advances in engineering, such as air– liquid interface culture and three-dimensional bioprinting, are highlighted for their potential to improve tissue structure and function. By outlining stage-specific evaluation and practical optimization strategies, this review provides a foundation for standardized protocols and the future development of physiologically relevant skin organoid systems for research and clinical applications.

Keywords
Skin organoid
Skin equivalent
Skin appendage organoid
Organoid construction
Pluripotent stem cell
Adult stem cell
Extracellular vesicle
Bioengineering
Funding
This work is supported by the National Natural Science Foundation of China (Grant No. 82572913, by Junyou Zhu).
Conflict of interest
The authors declare no conflict of interest.
References
  1. Guttman-Yassky E, Zhou L, Krueger JG. The skin as an immune organ: Tolerance versus effector responses and applications to food allergy and hypersensitivity reactions. J Allergy Clin Immunol. 2019;144(2):362-374. doi: 10.1016/j.jaci.2019.03.021
  2. Zhang C, Merana GR, Harris-Tryon T, Scharschmidt TC. Skin immunity: dissecting the complex biology of our body’s outer barrier. Mucosal Immunol. 2022;15(4):551-561. doi: 10.1038/s41385-022-00505-y
  3. Rheinwald JG, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975;6(3):331-343. doi: 10.1016/s0092-8674(75)80001-8
  4. Lee J, Rabbani CC, Gao H, et al. Hair-bearing human skin generated entirely from pluripotent stem cells. Nature. 2020;582(7812):399-404. doi: 10.1038/s41586-020-2352-3
  5. Wang X, Wang S, Guo B, et al. Human primary epidermal organoids enable modeling of dermatophyte infections. Cell Death Dis. 2021;12(1):35. doi: 10.1038/s41419-020-03330-y
  6. Boonekamp KE, Kretzschmar K, Wiener DJ, et al. Long-term expansion and differentiation of adult murine epidermal stem cells in 3D organoid cultures. Proc Natl Acad Sci USA. 2019;116(29):14630-14638. doi: 10.1073/pnas.1715272116
  7. Ahmed I, Sun J, Brown J, Khosrotehrani K, Shafiee A. An optimized protocol for generating appendage-bearing skin organoids from human-induced pluripotent stem cells. Biol Methods Protoc. 2024;9(1):bpae019. doi: 10.1093/biomethods/bpae019
  8. Huang Y, Ye Q, Wang J, et al. Recent progress in the identification and in vitro culture of skin organoids. Regen Ther. 2025;29:341-351. doi: 10.1016/j.reth.2025.01.001
  9. 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
  10. Kidwai FK, Liu H, Toh WS, et al. Differentiation of human embryonic stem cells into clinically amenable keratinocytes in an autogenic environment. J Invest Dermatol. 2013;133(3):618-628. doi: 10.1038/jid.2012.384
  11. Petrova A, Celli A, Jacquet L, et al. 3D In vitro model of a functional epidermal permeability barrier from human embryonic stem cells and induced pluripotent stem cells. Stem Cell Rep. 2014;2(5):675-689. doi: 10.1016/j.stemcr.2014.03.009
  12. Shamis Y, Hewitt KJ, Carlson MW, et al. Fibroblasts derived from human embryonic stem cells direct development and repair of 3D human skin equivalents. Stem Cell Res Ther. 2011;2(1):10. doi: 10.1186/scrt51
  13. Itoh M, Umegaki-Arao N, Guo Z, Liu L, Higgins CA, Christiano AM. Generation of 3D skin equivalents fully reconstituted from human induced pluripotent stem cells (iPSCs). PLoS ONE. 2013;8(10):e77673. doi: 10.1371/journal.pone.0077673
  14. Kim Y, Park N, Rim YA, et al. Establishment of a complex skin structure via layered co-culture of keratinocytes and fibroblasts derived from induced pluripotent stem cells. Stem Cell Res Ther. 2018;9(1):217. doi: 10.1186/s13287-018-0958-2
  15. Lee J, van der Valk WH, Serdy SA, et al. Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells. Nat Protoc. 2022;17(5):1266-1305. doi: 10.1038/s41596-022-00681-y
  16. Ahmed IA, Sun J, Kong MJ, Khosrotehrani K, Shafiee A. Generating Skin-Derived Precursor-Like Cells From Human-Induced Pluripotent Stem Cell-Derived Skin Organoids. Exp Dermatol. 2024;33(11):e70017. doi: 10.1111/exd.70017
  17. Diao J, Liu J, Wang S, et al. Sweat gland organoids contribute to cutaneous wound healing and sweat gland regeneration. Cell Death Dis. 2019;10(3):238. doi: 10.1038/s41419-019-1485-5
  18. Sun X, Xiang J, Chen R, et al. Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin. Adv Sci. 2021;8(22):e2103079. doi: 10.1002/advs.202103079
  19. Feldman A, Mukha D, Maor II, et al. Blimp1(+) cells generate functional mouse sebaceous gland organoids in vitro. Nat Commun. 2019;10(1):2348. doi: 10.1038/s41467-019-10261-6
  20. Gupta AC, Chawla S, Hegde A, et al. Establishment of an in vitro organoid model of dermal papilla of human hair follicle. J Cell Physiol. 2018;233(11):9015-9030. doi: 10.1002/jcp.26853
  21. Weber EL, Woolley TE, Yeh CY, Ou KL, Maini PK, Chuong CM. Self-organizing hair peg-like structures from dissociated skin progenitor cells: New insights for human hair follicle organoid engineering and Turing patterning in an asymmetric morphogenetic field. Exp Dermatol. 2019;28(4):355-366. doi: 10.1111/exd.13891
  22. Takagi R, Ishimaru J, Sugawara A, et al. Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model. Sci Adv. 2016;2(4):e1500887. doi: 10.1126/sciadv.1500887
  23. Gorkun-Roeder A, Mahajan N, Nomdedeu-Sancho G, et al. A Bioengineered Skin Organoid Platform for Modeling Human Skin Physiology and Cytotoxicity. Res Sq. 2025. doi: 10.21203/rs.3.rs-7989400/v1
  24. Zeng D, Li S, Du F, et al. Advances in engineered organoid models of skin for biomedical research. Burns Trauma. 2025;13:tkaf016. doi: 10.1093/burnst/tkaf016
  25. Ma J, Liu J, Gao D, et al. Establishment of Human Pluripotent Stem Cell-Derived Skin Organoids Enabled Pathophysiological Model of SARS-CoV-2 Infection. Adv Sci. 2022;9(7):e2104192. doi: 10.1002/advs.202104192
  26. Mostina M, Sun J, Sim SL, et al. Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells. Adv Healthc Mater. 2025;14(31):e02108. doi: 10.1002/adhm.202502108
  27. Sun J, Ahmed I, Brown J, Khosrotehrani K, Shafiee A. The empowering influence of air-liquid interface culture on skin organoid hair follicle development. Burns Trauma. 2025;13:tkae070. doi: 10.1093/burnst/tkae070
  28. Kwak S, Song CL, Lee J, et al. Development of pluripotent stem cell-derived epidermal organoids that generate effective extracellular vesicles in skin regeneration. Biomaterials. 2024;307:122522. doi: 10.1016/j.biomaterials.2024.122522
  29. Lee J, Koehler KR. Skin organoids: A new human model for developmental and translational research. Exp Dermatol. 2021;30(4):613-620. doi: 10.1111/exd.14292
  30. Sun H, Zhang YX, Li YM. Generation of Skin Organoids: Potential Opportunities and Challenges. Front Cell Dev Biol. 2021;9:709824. doi: 10.3389/fcell.2021.709824
  31. Li HY, Ren K, Wang C, Bu WB. Skin Organoid Research Progress and Potential Applications. Int J Dermatol Venereol. 2022;5(2):101-106. doi: 10.1097/JD9.0000000000000201
  32. Wang D, Majid M, Chen J, Wu C, Chen Y, Ni F. Skin Organoids for Disease Modelling, Drug Screening and Regenerative Medicine: Recent Advances and Future Perspectives. Wound Repair Regen. 2026;34(1):e70117. doi: 10.1111/wrr.70117
  33. Sandoval AGW, Gim KY, Huang JT, Koehler KR. Applications of Human Pluripotent Stem Cell-Derived Skin Organoids in Dermatology. J Invest Dermatol. 2023;143(10):1872-1876. doi: 10.1016/j.jid.2023.07.017
  34. Zhang YX, Zhou Y, Xiong YY, Li YM. Beyond skin deep: Revealing the essence of iPS cell-generated skin organoids in regeneration. Burns. 2024;50(9):107194. doi: 10.1016/j.burns.2024.06.011
  35. Hosseini M, Koehler KR, Shafiee A. Biofabrication of Human Skin with Its Appendages. Adv Healthc Mater. 2022;11(22):e2201626. doi: 10.1002/adhm.202201626
  36. Rimal R, Muduli S, Desai P, et al. Vascularized 3D Human Skin Models in the Forefront of Dermatological Research. Adv Healthc Mater. 2024;13(9):e2303351. doi: 10.1002/adhm.202303351
  37. Lakeh B, Shafiee A. Advancing dermatology with skin equivalents and organoids in pathophysiology and drug testing. Acta Biomater. 2025;207:120-130. doi: 10.1016/j.actbio.2025.10.008
  38. de Groot SC, Ulrich MMW, Gho CG, Huisman MA. Back to the Future: From Appendage Development Toward Future Human Hair Follicle Neogenesis. Front Cell Dev Biol. 2021;9:661787. doi: 10.3389/fcell.2021.661787
  39. Ji S, Zhu Z, Sun X, Fu X. Functional hair follicle regeneration: an updated review. Signal Transduct Target Ther. 2021;6(1):66. doi: 10.1038/s41392-020-00441-y
  40. Liu Y, Gao H, Chen H, et al. Sebaceous gland organoid engineering. Burns Trauma. 2024;12:tkae003. doi: 10.1093/burnst/tkae003
  41. Yao X, Ding R, Chuanjian Y, et al. Hair follicle organoids: advances in construction, applications, and translational challenges. Front Cell Dev Biol. 2026;14. doi: 10.3389/fcell.2026.1836905
  42. Zoio P, Oliva A. Skin-on-a-Chip Technology: Microengineering Physiologically Relevant In Vitro Skin Models. Pharmaceutics. 2022;14(3). doi: 10.3390/pharmaceutics14030682
  43. Cho SW, Malick H, Kim SJ, Grattoni A. Advances in Skin-on-a-Chip Technologies for Dermatological Disease Modeling. J Invest Dermatol. 2024;144(8):1707-1715. doi: 10.1016/j.jid.2024.01.031
  44. Ismayilzada N, Tarar C, Dabbagh SR, et al. Skin-on-a-chip technologies towards clinical translation and commercialization. Biofabrication. 2024;16(4). doi: 10.1088/1758-5090/ad5f55
  45. Teertam SK, Setaluri V, Ayuso JM. Advances in Microengineered Platforms for Skin Research. JID Innov. 2025;5(1):100315. doi: 10.1016/j.xjidi.2024.100315
  46. Huang Y, Wu X, Xu Y, et al. Organoids/organs-on-chips towards biomimetic human artificial skin. Burns Trauma. 2025;13:tkaf029. doi: 10.1093/burnst/tkaf029
  47. Lee T, Kyung SY, Kwon M, Park B, Ko J. Innovations in skin microphysiological systems for nonclinical testing and FDA modernization. Microsyst Nanoeng. 2026;12(1):44. doi: 10.1038/s41378-025-01149-1
  48. Test No. 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method. Paris, France: OECD Publishing; 2025. doi: 10.1787/9789264242845-en
  49. Sanches PL, Vieira Carias RB, Alves GG, et al. Pre-validation of a novel reconstructed skin equivalent model for skin irritation and nanoparticle risk assessment. Nanoscale Adv. 2025;7(5):1353-1367. doi: 10.1039/d4na00804a
  50. Portugal-Cohen M, Cohen D, Kohen R, Oron M. Exploitation of alternative skin models from academia to industry: proposed functional categories to answer needs and regulation demands. Front Physiol. 2023;14:1215266. doi: 10.3389/fphys.2023.1215266
  51. Rhee S, Xia C, Chandra A, et al. Full-Thickness Perfused Skin-on-a-Chip with In Vivo-Like Drug Response for Drug and Cosmetics Testing. Bioengineering. 2024;11(11). doi: 10.3390/bioengineering11111055
  52. Sun S, Jin L, Zheng Y, Zhu J. Modeling human HSV infection via a vascularized immune-competent skin-on-chip platform. Nat Commun. 2022;13(1):5481. doi: 10.1038/s41467-022-33114-1
  53. Gledhill K, Guo Z, Umegaki-Arao N, Higgins CA, Itoh M, Christiano AM. Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells. PLoS ONE. 2015;10(8):e0136713. doi: 10.1371/journal.pone.0136713
  54. Domingues S, Darle A, Masson Y, et al. Clinical Grade Human Pluripotent Stem Cell-Derived Engineered Skin Substitutes Promote Keratinocytes Wound Closure In Vitro. Cells. 2022;11(7). doi: 10.3390/cells11071151
  55. Lee J, Bӧscke R, Tang PC, Hartman BH, Heller S, Koehler KR. Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids. Cell Rep. 2018;22(1):242-254. doi: 10.1016/j.celrep.2017.12.007
  56. Shafiee A, Sun J, Ahmed IA, et al. Development of Physiologically Relevant Skin Organoids from Human Induced Pluripotent Stem Cells. Small. 2024;20(16):e2304879. doi: 10.1002/smll.202304879
  57. Liu X, Ye Y, Chen J, et al. Advances in sweat gland organoids: construction, molecular mechanisms, and challenges. Stem Cell Res Ther. 2025;16(1):586. doi: 10.1186/s13287-025-04689-5
  58. Abaci HE, Coffman A, Doucet Y, et al. Tissue engineering of human hair follicles using a biomimetic developmental approach. Nat Commun. 2018;9(1):5301. doi: 10.1038/s41467-018-07579-y
  59. Ebner-Peking P, Krisch L, Wolf M, et al. Self-assembly of differentiated progenitor cells facilitates spheroid human skin organoid formation and planar skin regeneration. Theranostics. 2021;11(17):8430-8447. doi: 10.7150/thno.59661
  60. Sugiyama E, Nanmo A, Nie X, et al. Large-Scale Preparation of Hair Follicle Germs Using a Microfluidic Device. ACS Biomater Sci Eng. 2024;10(2):998-1005. doi: 10.1021/acsbiomaterials.3c01346
  61. Kageyama T, Yoshimura C, Myasnikova D, et al. Spontaneous hair follicle germ (HFG) formation in vitro, enabling the large-scale production of HFGs for regenerative medicine. Biomaterials. 2018;154:291-300. doi: 10.1016/j.biomaterials.2017.10.056
  62. Catarino MC, Schuck CD, Dechiario L, Karande P. Incorporation of hair follicles in 3D bioprinted models of human skin. Sci Adv. 2023;9(41):eadg0297. doi: 10.1126/sciadv.adg0297
  63. Yin X, Mead BE, Safaee H, Langer R, Karp JM, Levy O. Engineering Stem Cell Organoids. Cell Stem Cell. 2016;18(1):25-38. doi: 10.1016/j.stem.2015.12.005
  64. Nasiri R, Zhu Y, de Barros NR. Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening. Biosensors. 2024;14(2). doi: 10.3390/bios14020086
  65. Itoh M, Kiuru M, Cairo MS, Christiano AM. Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells. Proc Natl Acad Sci USA. 2011;108(21):8797-8802. doi: 10.1073/pnas.1100332108
  66. Neumayer G, Torkelson JL, Li S, et al. A scalable and cGMP-compatible autologous organotypic cell therapy for Dystrophic Epidermolysis Bullosa. Nat Commun. 2024;15(1):5834. doi: 10.1038/s41467-024-49400-z
  67. Kogut I, Roop DR, Bilousova G. Differentiation of human induced pluripotent stem cells into a keratinocyte lineage. Methods Mol Biol. 2014;1195:1-12. doi: 10.1007/7651_2013_64
  68. Ali G, Abdelalim EM. Directed differentiation of human pluripotent stem cells into epidermal keratinocyte-like cells. STAR Protoc. 2022;3(3):101613. doi: 10.1016/j.xpro.2022.101613
  69. Koch PJ, Webb S, Gugger JA, Salois MN, Koster MI. Differentiation of Human Induced Pluripotent Stem Cells into Keratinocytes. Curr Protoc. 2022;2(4):e408. doi: 10.1002/cpz1.408
  70. Garriga-Cerda L, Pappalardo A, Lee CY, Kysar J, Myers K, Abaci HE. IPSC-derived organoid-sourced skin cells enable functional 3D skin modeling of recessive dystrophic epidermolysis bullosa. J Tissue Eng. 2025;16:20417314251397594. doi: 10.1177/20417314251397594
  71. Smith L, Bunton D, Finch M, Przyborski S. Bioengineering a Human Dermal Equivalent Using Induced Pluripotent Stem Cell-Derived Fibroblasts to Support the Formation of a Full- Thickness Skin Construct. Cells. 2025;14(14):1044. doi: 10.3390/cells14141044
  72. Coutier J, Bonnette M, Martineau S, et al. Human-Induced Pluripotent Stem Cell‒Derived Keratinocytes, a Useful Model to Identify and Explore the Pathological Phenotype of Epidermolysis Bullosa Simplex. J Invest Dermatol. 2022;142(10):2695-2705.e11. doi: 10.1016/j.jid.2022.04.009
  73. Ma J, Li W, Cao R, et al. Application of an iPSC-Derived Organoid Model for Localized Scleroderma Therapy. Adv Sci. 2022;9(16):e2106075. doi: 10.1002/advs.202106075
  74. Shin H, Kim SE, Kim CY, et al. Skin irritation testing using human iPSCs derived 3D skin equivalent model. PLoS ONE. 2025;20(8):e0330306. doi: 10.1371/journal.pone.0330306
  75. Yang R, Zheng Y, Burrows M, et al. Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells. Nat Commun. 2014;5(1):3071. doi: 10.1038/ncomms4071
  76. Moradi S, Mahdizadeh H, Šarić T, et al. Research and therapy with induced pluripotent stem cells (iPSCs): social, legal, and ethical considerations. Stem Cell Res Ther. 2019;10(1):341. doi: 10.1186/s13287-019-1455-y
  77. Liang G, Zhang Y. Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective. Cell Res. 2013;23(1):49-69. doi: 10.1038/cr.2012.175
  78. Scesa G, Adami R, Bottai D. iPSC Preparation and Epigenetic Memory: Does the Tissue Origin Matter? Cells. 2021;10(6):1470. doi: 10.3390/cells10061470
  79. Jensen KB, Little MH. Organoids are not organs: Sources of variation and misinformation in organoid biology. Stem Cell Rep. 2023;18(6):1255-1270. doi: 10.1016/j.stemcr.2023.05.009
  80. Jiang J, Liu W, Wang M, et al. Metabolic adaptation drives self-organization during skin organoid morphogenesis. Nat Commun. 2026;17(1). doi: 10.1038/s41467-026-71709-0
  81. Xie X, Tong X, Li Z, et al. Use of mouse primary epidermal organoids for USA300 infection modeling and drug screening. Cell Death Dis. 2023;14(1):15. doi: 10.1038/s41419-022-05525-x
  82. Zhang T, Sheng S, Cai W, et al. 3-D bioprinted human-derived skin organoids accelerate full-thickness skin defects repair. Bioact Mater. 2024;42:257-269. doi: 10.1016/j.bioactmat.2024.08.036
  83. Fu J, Hsu W. Epidermal Wnt controls hair follicle induction by orchestrating dynamic signaling crosstalk between the epidermis and dermis. J Invest Dermatol. 2013;133(4):890- 898. doi: 10.1038/jid.2012.407
  84. Kageyama T, Chun YS, Fukuda J. Hair follicle germs containing vascular endothelial cells for hair regenerative medicine. Sci Rep. 2021;11(1):624. doi: 10.1038/s41598-020-79722-z
  85. Kageyama T, Anakama R, Hamano S, et al. Hair Follicle Organoids Using Human iPSC-Derived Ectodermal Precursor Cells for Hair Regenerative Medicine. ACS Biomater Sci Eng. 2026;12(3):1704-1714. doi: 10.1021/acsbiomaterials.5c01780
  86. Veraitch O, Kobayashi T, Imaizumi Y, et al. Human induced pluripotent stem cell-derived ectodermal precursor cells contribute to hair follicle morphogenesis in vivo. J Invest Dermatol. 2013;133(6):1479-1488. doi: 10.1038/jid.2013.7
  87. Veraitch O, Mabuchi Y, Matsuzaki Y, et al. Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY- 1(+) mesenchymal cells. Sci Rep. 2017;7(1):42777. doi: 10.1038/srep42777
  88. Lei M, Schumacher LJ, Lai YC, et al. Self-organization process in newborn skin organoid formation inspires strategy to restore hair regeneration of adult cells. Proc Natl Acad Sci USA. 2017;114(34):E7101-E7110. doi: 10.1073/pnas.1700475114
  89. Higgins CA, Chen JC, Cerise JE, Jahoda CAB, Christiano AM. Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth. Proc Natl Acad Sci USA. 2013;110(49):19679-19688. doi: 10.1073/pnas.1309970110
  90. Zhao Q, Li N, Zhang H, et al. Chemically induced transformation of human dermal fibroblasts to hair-inducing dermal papilla-like cells. Cell Prolif. 2019;52(5):e12652. doi: 10.1111/cpr.12652
  91. Su Y, Wen J, Zhu J, et al. Pre-aggregation of scalp progenitor dermal and epidermal stem cells activates the WNT pathway and promotes hair follicle formation in in vitro and in vivo systems. Stem Cell Res Ther. 2019;10(1):403. doi: 10.1186/s13287-019-1504-6
  92. Ryu JO, Seong YJ, Lee E, Lee SY, Lee DW. Applications and research trends in organoid based infectious disease models. Sci Rep. 2025;15(1):25185. doi: 10.1038/s41598-025-07816-7
  93. Schmidt M, Hansmann F, Loeffler-Wirth H, Zouboulis CC, Binder H, Schneider MR. A spatial portrait of the human sebaceous gland transcriptional program. J Biol Chem. 2024;300(7):107442. doi: 10.1016/j.jbc.2024.107442
  94. Klaka P, Grüdl S, Banowski B, et al. A novel organotypic 3D sweat gland model with physiological functionality. PLoS ONE. 2017;12(8):e0182752. doi: 10.1371/journal.pone.0182752
  95. Huang S, Yao B, Xie J, Fu X. 3D bioprinted extracellular matrix mimics facilitate directed differentiation of epithelial progenitors for sweat gland regeneration. Acta Biomater. 2016;32:170-177. doi: 10.1016/j.actbio.2015.12.039
  96. Xiang J, Chen H, Zhang H, et al. Restoring sweat gland function in mice using regenerative sweat gland cells derived from chemically reprogrammed human epidermal keratinocytes. Sci Bull. 2024;69(24):3908-3924. doi: 10.1016/j.scib.2024.11.003
  97. Biedermann T, Pontiggia L, Böttcher-Haberzeth S, et al. Human eccrine sweat gland cells can reconstitute a stratified epidermis. J Invest Dermatol. 2010;130(8):1996-2009. doi: 10.1038/jid.2010.83
  98. Li H, Chen L, Zeng S, et al. Matrigel basement membrane matrix induces eccrine sweat gland cells to reconstitute sweat gland-like structures in nude mice. Exp Cell Res. 2015;332(1):67-77. doi: 10.1016/j.yexcr.2015.01.014
  99. Huang Z, Zhen Y, Yin W, Ma Z, Zhang L. Shh promotes sweat gland cell maturation in three-dimensional culture. Cell Tissue Bank. 2016;17(2):317-325. doi: 10.1007/s10561-016-9548-7
  100. Andl T, Reddy ST, Gaddapara T, Millar SE. WNT signals are required for the initiation of hair follicle development. Dev Cell. 2002;2(5):643-653. doi: 10.1016/s1534-5807(02)00167-3
  101. Zhang Y, Tomann P, Andl T, et al. Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction. Dev Cell. 2009;17(1):49- 61. doi: 10.1016/j.devcel.2009.05.011
  102. Zhu XJ, Liu Y, Dai ZM, et al. BMP-FGF signaling axis mediates Wnt-induced epidermal stratification in developing mammalian skin. PLoS Genet. 2014;10(10):e1004687. doi: 10.1371/journal.pgen.1004687
  103. Myung PS, Takeo M, Ito M, Atit RP. Epithelial Wnt ligand secretion is required for adult hair follicle growth and regeneration. J Invest Dermatol. 2013;133(1):31-41. doi: 10.1038/jid.2012.230
  104. Tchieu J, Zimmer B, Fattahi F, et al. A Modular Platform for Differentiation of Human PSCs into All Major Ectodermal Lineages. Cell Stem Cell. 2017;21(3):399-410.e7. doi: 10.1016/j.stem.2017.08.015
  105. Cui CY, Yin M, Sima J, et al. Involvement of Wnt, Eda and Shh at defined stages of sweat gland development. Development. 2014;141(19):3752-3760. doi: 10.1242/dev.109231
  106. Lu CP, Polak L, Keyes BE, Fuchs E. Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision. Science. 2016;354(6319). doi: 10.1126/science.aah6102
  107. Sick S, Reinker S, Timmer J, Schlake T. WNT and DKK determine hair follicle spacing through a reaction-diffusion mechanism. Science. 2006;314(5804):1447-1450. doi: 10.1126/science.1130088
  108. Pummila M, Fliniaux I, Jaatinen R, et al. Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression. Development. 2007;134(1):117-125. doi: 10.1242/dev.02708
  109. Huh SH, Närhi K, Lindfors PH, et al. Fgf20 governs formation of primary and secondary dermal condensations in developing hair follicles. Genes Dev. 2013;27(4):450-458. doi: 10.1101/gad.198945.112
  110. Biggs LC, Mäkelä OJ, Myllymäki SM, et al. Hair follicle dermal condensation forms via Fgf20 primed cell cycle exit, cell motility, and aggregation. eLife. 2018;7. doi: 10.7554/eLife.36468
  111. Tokuyama E, Nagai Y, Takahashi K, Kimata Y, Naruse K. Mechanical Stretch on Human Skin Equivalents Increases the Epidermal Thickness and Develops the Basement Membrane. PLoS ONE. 2015;10(11):e0141989. doi: 10.1371/journal.pone.0141989
  112. Zoio P, Lopes-Ventura S, Marto J, Oliva A. Open-source human skin model with an in vivo-like barrier for drug testing. ALTEX. 2022;39(3):405-418. doi: 10.14573/altex.2111182
  113. Rosdy M, Clauss LC. Terminal epidermal differentiation of human keratinocytes grown in chemically defined medium on inert filter substrates at the air-liquid interface. J Invest Dermatol. 1990;95(4):409-414. doi: 10.1111/1523-1747.ep12555510
  114. De Henau CMS, Lorrain V, Flesseman MP, Ramovs V, Raymond K. Generation of Human Induced Pluripotent Stem Cell-derived Planar Hair-bearing Skin Organoids Using an Air-Liquid Interface Culture System. JoVE. 2025;(224). doi: 10.3791/69088
  115. Chen Z, Kalhori D, Rakhshani F, et al. Hydrodynamically generated multilayer skin spheroids enable in vitro screening of biologically active ingredients and toxicity tests. Sci Adv. 2025;11(19):eadu1251. doi: 10.1126/sciadv.adu1251
  116. Fernandez-Carro E, Angenent M, Gracia-Cazaña T, Gilaberte Y, Alcaine C, Ciriza J. Modeling an Optimal 3D Skin-on- Chip within Microfluidic Devices for Pharmacological Studies. Pharmaceutics. 2022;14(7):1417. doi: 10.3390/pharmaceutics14071417
  117. Cruz-Acuña R, Quirós M, Huang S, et al. PEG-4MAL hydrogels for human organoid generation, culture, and in vivo delivery. Nat Protoc. 2018;13(9):2102-2119. doi: 10.1038/s41596-018-0036-3
  118. Wolf MT, Daly KA, Brennan-Pierce EP, et al. A hydrogel derived from decellularized dermal extracellular matrix. Biomaterials. 2012;33(29):7028-7038. doi: 10.1016/j.biomaterials.2012.06.051
  119. Di Francesco D, Marcello E, Casarella S, et al. Characterization of a decellularized pericardium extracellular matrix hydrogel for regenerative medicine: insights on animal-to-animal variability. Front Bioeng Biotechnol. 2024;12:1452965. doi: 10.3389/fbioe.2024.1452965
  120. Sarmin AM, Connelly JT. Fabrication of Human Skin Equivalents Using Decellularized Extracellular Matrix. Curr Protoc. 2022;2(3):e393. doi: 10.1002/cpz1.393
  121. Gjorevski N, Sachs N, Manfrin A, et al. Designer matrices for intestinal stem cell and organoid culture. Nature. 2016;539(7630):560-564. doi: 10.1038/nature20168
  122. Chaudhuri O, Gu L, Klumpers D, et al. Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat Mater. 2016;15(3):326-334. doi: 10.1038/nmat4489
  123. Aisenbrey EA, Murphy WL. Synthetic alternatives to Matrigel. Nat Rev Mater. 2020;5(7):539-551. doi: 10.1038/s41578-020-0199-8
  124. Kozlowski MT, Crook CJ, Ku HT. Towards organoid culture without Matrigel. Commun Biol. 2021;4(1):1387. doi: 10.1038/s42003-021-02910-8
  125. Fernandez-Carro E, Remacha AR, Orera I, et al. Human Dermal Decellularized ECM Hydrogels as Scaffolds for 3D In Vitro Skin Aging Models. Int J Mol Sci. 2024;25(7):4020. doi: 10.3390/ijms25074020
  126. Belviso I, Romano V, Sacco AM, et al. Decellularized Human Dermal Matrix as a Biological Scaffold for Cardiac Repair and Regeneration. Front Bioeng Biotechnol. 2020;8:229. doi: 10.3389/fbioe.2020.00229
  127. Montero A, Atienza C, Elvira C, Jorcano JL, Velasco D. Hyaluronic acid-fibrin hydrogels show improved mechanical stability in dermo-epidermal skin substitutes. Mater Sci Eng C Mater Biol Appl. 2021;128:112352. doi: 10.1016/j.msec.2021.112352
  128. Bindi B, Perioli A, Melo P, Mattu C, Ferreira AM. Bioinspired Collagen/Hyaluronic Acid/Fibrin-Based Hydrogels for Soft Tissue Engineering: Design, Synthesis, and In Vitro Characterization. J Funct Biomater. 2023;14(10):495. doi: 10.3390/jfb14100495
  129. Guo X, Liu B, Zhang Y, et al. Decellularized extracellular matrix for organoid and engineered organ culture. J Tissue Eng. 2024;15:20417314241300386. doi: 10.1177/20417314241300386
  130. Tan CT, Leo ZY, Lim CY. Generation and integration of hair follicle-primed spheroids in bioengineered skin constructs. Biomed Mater. 2022;17(6):061001. doi: 10.1088/1748-605X/ac99c6
  131. Chen H, Ma X, Gao T, Zhao W, Xu T, Liu Z. Robot-assisted in situ bioprinting of gelatin methacrylate hydrogels with stem cells induces hair follicle-inclusive skin regeneration. Biomed Pharm. 2023;158:114140. doi: 10.1016/j.biopha.2022.114140
  132. Nanmo A, Yan L, Asaba T, Wan L, Kageyama T, Fukuda J. Bioprinting of hair follicle germs for hair regenerative medicine. Acta Biomater. 2023;165:50-59. doi: 10.1016/j.actbio.2022.06.021
  133. Quintard C, Tubbs E, Jonsson G, et al. A microfluidic platform integrating functional vascularized organoids-on-chip. Nat Commun. 2024;15(1):1452. doi: 10.1038/s41467-024-45710-4
  134. Huang J, Fu D, Wu X, et al. One-step generation of core-shell biomimetic microspheres encapsulating double-layer cells using microfluidics for hair regeneration. Biofabrication. 2023;15(2):025007. doi: 10.1088/1758-5090/acb107
  135. Sriram G, Bigliardi PL, Bigliardi-Qi M. Full-Thickness Human Skin Equivalent Models of Atopic Dermatitis. In: Methods in Molecular Biology. New York: Springer; 2018:367- 383. doi: 10.1007/7651_2018_163
  136. Lee S, Rim YA, Kim J, et al. Guidelines for Manufacturing and Application of Organoids: Skin. Int J Stem Cells. 2024;17(2):182-193. doi: 10.15283/ijsc24045
  137. Choy Buentello D, Koch LS, Trujillo-de Santiago G, Alvarez MM, Broersen K. Use of standard U-bottom and V-bottom well plates to generate neuroepithelial embryoid bodies. PLoS ONE. 2022;17(5):e0262062. doi: 10.1371/journal.pone.0262062
  138. Beck LE, Lee J, Coté C, et al. Systematically quantifying morphological features reveals constraints on organoid phenotypes. Cell Syst. 2022;13(7):547-560.e3. doi: 10.1016/j.cels.2022.05.008
  139. Linares-Gonzalez L, Rodenas-Herranz T, Campos F, Ruiz- Villaverde R, Carriel V. Basic Quality Controls Used in Skin Tissue Engineering. Life. 2021;11(10):1033. doi: 10.3390/life11101033
  140. Bataillon M, Lelièvre D, Chapuis A, et al. Characterization of a New Reconstructed Full Thickness Skin Model, T-SkinTM, and its Application for Investigations of Anti-Aging Compounds. Int J Mol Sci. 2019;20(9):2240. doi: 10.3390/ijms20092240
  141. Tanuma-Takahashi A, Inoue M, Kajiwara K, et al. Restoration of keratinocytic phenotypes in autonomous trisomy-rescued cells. Stem Cell Res Ther. 2021;12(1):476. doi: 10.1186/s13287-021-02448-w
  142. Ramovs V, Janssen H, Fuentes I, et al. Characterization of the epidermal-dermal junction in hiPSC-derived skin organoids. Stem Cell Rep. 2022;17(6):1279-1288. doi: 10.1016/j.stemcr.2022.04.008
  143. Kim SW, Park KC, Kim HJ, et al. Effects of collagen IV and laminin on the reconstruction of human oral mucosa. J Biomed Mater Res. 2001;58(1):108-112. doi: 10.1002/1097-4636(2001)58:1<108::aid-jbm160>3.0.co;2-i
  144. Purba TS, Haslam IS, Shahmalak A, Bhogal RK, Paus R. Mapping the expression of epithelial hair follicle stem cell-related transcription factors LHX2 and SOX9 in the human hair follicle. Exp Dermatol. 2015;24(6):462-467. doi: 10.1111/exd.12700
  145. Chovatiya G, Ghuwalewala S, Walter LD, Cosgrove BD, Tumbar T. High-resolution single-cell transcriptomics reveals heterogeneity of self-renewing hair follicle stem cells. Exp Dermatol. 2021;30(4):457-471. doi: 10.1111/exd.14262
  146. Rhee H, Polak L, Fuchs E. Lhx2 maintains stem cell character in hair follicles. Science. 2006;312(5782):1946-1949. doi: 10.1126/science.1128004
  147. Wisdom EC, Aduba DCJ, Lewis O, et al. A Novel Approach to Pattern Dermal Papilla Spheroids in Dermal-Epidermal Composites Using Non-Adherent Microwell Arrays. Bioengineering. 2025;12(12):1281. doi: 10.3390/bioengineering12121281
  148. Abreu CM, Cerqueira MT, Pirraco RP, Gasperini L, Reis RL, Marques AP. Rescuing key native traits in cultured dermal papilla cells for human hair regeneration. J Adv Res. 2021;30:103-112. doi: 10.1016/j.jare.2020.10.006
  149. Yang J, Wang Z, Zhou H, et al. Insights into human melanocyte development and characteristics through pluripotent stem cells combined with single-cell sequencing. iScience. 2025;28(5):112373. doi: 10.1016/j.isci.2025.112373
  150. Cichorek M, Wachulska M, Stasiewicz A, Tymińska A. Skin melanocytes: biology and development. Postepy Dermatol Alergol. 2013;30(1):30-41. doi: 10.5114/pdia.2013.33376
  151. Kervarrec T, Samimi M, Hesbacher S, et al. Merkel Cell Polyomavirus T Antigens Induce Merkel Cell-Like Differentiation in GLI1-Expressing Epithelial Cells. Cancers. 2020;12(7):1989. doi: 10.3390/cancers12071989
  152. Lesko MH, Driskell RR, Kretzschmar K, Goldie SJ, Watt FM. Sox2 modulates the function of two distinct cell lineages in mouse skin. Dev Biol. 2013;382(1):15-26. doi: 10.1016/j.ydbio.2013.08.004
  153. Liu Y, Ji S, Gao H, et al. Sebaceous gland reprogramming with a single gene, PPARG, and small molecules. Signal Transduct Target Ther. 2023;8(1):286. doi: 10.1038/s41392-023-01531-3
  154. Dahlhoff M, Camera E, Picardo M, et al. PLIN2, the major perilipin regulated during sebocyte differentiation, controls sebaceous lipid accumulation in vitro and sebaceous gland size in vivo. Biochim Biophys Acta. 2013;1830(10):4642-4649. doi: 10.1016/j.bbagen.2013.05.016
  155. Inoue R, Sohara E, Rai T, et al. Immunolocalization and translocation of aquaporin-5 water channel in sweat glands. J Dermatol Sci. 2013;70(1):26-33. doi: 10.1016/j.jdermsci.2013.01.013
  156. Wimmer RA, Leopoldi A, Aichinger M, et al. Human blood vessel organoids as a model of diabetic vasculopathy. Nature. 2019;565(7740):505-510. doi: 10.1038/s41586-018-0858-8
  157. Gong L, Zhang Y, Zhu Y, et al. Rapid generation of functional vascular organoids via simultaneous transcription factor activation of endothelial and mural lineages. Cell Stem Cell. 2025;32(8):1200-1217.e6. doi: 10.1016/j.stem.2025.05.014
  158. Romani N, Clausen BE, Stoitzner P. Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunol Rev. 2010;234(1):120-141. doi: 10.1111/j.0105-2896.2009.00886.x
  159. Alexander FA, Eggert S, Wiest J. Skin-on-a-Chip: Transepithelial Electrical Resistance and Extracellular Acidification Measurements through an Automated Air- Liquid Interface. Genes. 2018;9(2):114. doi: 10.3390/genes9020114
  160. Mannweiler R, Bergmann S, Vidal-Y-Sy S, Brandner JM, Günzel D. Direct assessment of individual skin barrier components by electrical impedance spectroscopy. Allergy. 2021;76(10):3094-3106. doi: 10.1111/all.14851
  161. Neupane R, Boddu SHS, Renukuntla J, Babu RJ, Tiwari AK. Alternatives to Biological Skin in Permeation Studies: Current Trends and Possibilities. Pharmaceutics. 2020;12(2):152. doi: 10.3390/pharmaceutics12020152
  162. Li T, Li X, Xiang X, et al. Regenerative Hair Pigmentation via Skin Organoids: Adaptive Patterning Mediated by Collagen VI and Semaphorin 3C. Adv Sci. 2025;12(36):e02436. doi: 10.1002/advs.202502436
  163. Sun H, Shen W, Zhong HJ, Li YM. Advancing skin organoids in dermatology: Current limitations and future horizons. J Am Acad Dermatol. 2026;94(3):e211-e212. doi: 10.1016/j.jaad.2025.08.131
  164. Quan T. Molecular insights of human skin epidermal and dermal aging. J Dermatol Sci. 2023;112(2):48-53. doi: 10.1016/j.jdermsci.2023.08.006
  165. Shakel Z, Costa Lima SA, Reis S. Strategies to make human skin models based on cellular senescence for ageing research. Ageing Res Rev. 2024;100:102430. doi: 10.1016/j.arr.2024.102430
  166. Nwokoye PN, Abilez OJ. Bioengineering methods for vascularizing organoids. Cell Rep Methods. 2024;4(6):100779. doi: 10.1016/j.crmeth.2024.100779
  167. Xie J, Yang Q, Zhang Y, Zheng K, Geng H, Wu Y. The Bioengineering of Microspheric Skin Organoids and Their Application in Drug Screening. Adv Sci. 2025;12(22):e2416863. doi: 10.1002/advs.202416863
  168. Mohamed NV, Larroquette F, Beitel LK, Fon EA, Durcan TM. One Step Into the Future: New iPSC Tools to Advance Research in Parkinson’s Disease and Neurological Disorders. J Parkinsons Dis. 2019;9(2):265-281. doi: 10.3233/JPD-181515
  169. Quílez C, Jeon EY, Pappalardo A, Pathak P, Abaci HE. Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle-Shaped Microfluidic Device. Adv Healthc Mater. 2024;13(20):e2400405. doi: 10.1002/adhm.202400405
  170. Heo JH, Kang D, Seo SJ, Jin Y. Engineering the Extracellular Matrix for Organoid Culture. Int J Stem Cells. 2022;15(1):60- 69. doi: 10.15283/ijsc21190
  171. Mulero-Russe A, García AJ. Engineered Synthetic Matrices for Human Intestinal Organoid Culture and Therapeutic Delivery. Adv Mater. 2024;36(9):e2307678. doi: 10.1002/adma.202307678
  172. Fang Y, Eglen RM. Three-Dimensional Cell Cultures in Drug Discovery and Development. SLAS Discov. 2017;22(5):456- 472. doi: 10.1177/1087057117696795
  173. Mansoury M, Hamed M, Karmustaji R, Al Hannan F, Safrany ST. The edge effect: A global problem. The trouble with culturing cells in 96-well plates. Biochem Biophys Rep. 2021;26:100987. doi: 10.1016/j.bbrep.2021.100987
  174. Yip HYK, Papa A. Generation and functional characterization of murine mammary organoids. STAR Protoc. 2021;2(3):100765. doi: 10.1016/j.xpro.2021.100765
  175. Li P, Pachis ST, Xu G, et al. Mpox virus infection and drug treatment modelled in human skin organoids. Nat Microbiol. 2023;8(11):2067-2079. doi: 10.1038/s41564-023-01489-6
  176. Li J, Ma J, Cao R, et al. A skin organoid-based infection platform identifies an inhibitor specific for HFMD. Nat Commun. 2025;16(1):2513. doi: 10.1038/s41467-025-57610-2
  177. Costa Gagosian VS, Coronel R, Buss BC, et al. In Vitro Skin Models as Non-Animal Methods for Dermal Drug Development and Safety Assessment. Pharmaceutics. 2025;17(10):1342. doi: 10.3390/pharmaceutics17101342
  178. Wang Z, Zhao F, Lang H, et al. Organoids in skin wound healing. Burns Trauma. 2025;13:tkae077. doi: 10.1093/burnst/tkae077
  179. Kabashima K, Honda T, Ginhoux F, Egawa G. The immunological anatomy of the skin. Nat Rev Immunol. 2019;19(1):19-30. doi: 10.1038/s41577-018-0084-5
  180. Quaresma JAS. Organization of the Skin Immune System and Compartmentalized Immune Responses in Infectious Diseases. Clin Microbiol Rev. 2019;32(4). doi: 10.1128/CMR.00034-18
  181. Gopee NH, Winheim E, Olabi B, et al. A prenatal skin atlas reveals immune regulation of human skin morphogenesis. Nature. 2024;635(8039):679-689. doi: 10.1038/s41586-024-08002-x
  182. Rockel AF, Wagner N, Spenger P, Ergün S, Wörsdörfer P. Neuro-mesodermal assembloids recapitulate aspects of peripheral nervous system development in vitro. Stem Cell Rep. 2023;18(5):1155-1165. doi: 10.1016/j.stemcr.2023.03.012
  183. Onesto MM, Kim JI, Pasca SP. Assembloid models of cell-cell interaction to study tissue and disease biology. Cell Stem Cell. 2024;31(11):1563-1573. doi: 10.1016/j.stem.2024.09.017
  184. Kim JI, Imaizumi K, Jurjuț O, et al. Human assembloid model of the ascending neural sensory pathway. Nature. 2025;642(8066):143-153. doi: 10.1038/s41586-025-08808-3
  185. Schutte SC, Kadakia F, Davidson S. Skin-Nerve Co-Culture Systems for Disease Modeling and Drug Discovery. Tissue Eng Part C Methods. 2021;27(2):89-99. doi: 10.1089/ten.TEC.2020.0296
  186. Auyeung KL, Kim BS. Emerging concepts in neuropathic and neurogenic itch. Ann Allergy Asthma Immunol. 2023;131(5):561-566. doi: 10.1016/j.anai.2023.08.008
  187. Yosipovitch G, Kim B, Luger T, et al. Similarities and differences in peripheral itch and pain pathways in atopic dermatitis. J Allergy Clin Immunol. 2024;153(4):904-912. doi: 10.1016/j.jaci.2023.10.034
  188. Zhang Z, Ren D, Tang J, Guo S. Research progress on the role of peripheral nerves in wound healing. J Zhejiang Univ. 2025;54(5):628-636. doi: 10.3724/zdxbyxb-2025-0032
  189. Noble A, Qubrosi R, Cariba S, Favaro K, Payne SL. Neural dependency in wound healing and regeneration. Dev Dyn. 2024;253(2):181-203. doi: 10.1002/dvdy.650
  190. Abdal Dayem A, Kwak Y, Jeun H, Cho SG. Recent Insights into Organoid-Derived Extracellular Vesicles and Their Biomedical Applications. J Pers Med. 2025;15(10):492. doi: 10.3390/jpm15100492
  191. Miao X, Kong K, Rong K, et al. Construction of biomimetic gradient-structured cartilage organoids and mechanistic study of their application for cartilage rejuvenation. Bioact Mater. 2026;59:579-594. doi: 10.1016/j.bioactmat.2025.12.052
  192. Kim D, Youn J, Kim J, Lee J, Yoon J, Kim DS. From organoid culture to manufacturing: technologies for reproducible and scalable organoid production. npj Biomed Innov. 2026;3(1):12. doi: 10.1038/s44385-025-00054-6
  193. Ahn SJ, Lee S, Kwon D, et al. Essential Guidelines for Manufacturing and Application of Organoids. Int J Stem Cells. 2024;17(2):102-112. doi: 10.15283/ijsc24047
  194. European Commission. Guidelines on Good Manufacturing Practice Specific to Advanced Therapy Medicinal Products. EudraLex Volume 4: Good Manufacturing Practice. European Commission. 2017. Accessed July 9, 2026. https:// health.ec.europa.eu/document/download/ad33d9dd- 03f0-4bef-af53-21308ce2187d_en?filename=2017_11_22_ guidelines_gmp_for_atmps.pdf
  195. US Food and Drug Administration. Considerations for the Use of Human- and Animal-Derived Materials in the Manufacture of Cellular and Gene Therapy and Tissue- Engineered Medical Products: Draft Guidance for Industry. US Food and Drug Administration. 2024. Accessed July 9, 2026. https://www.fda.gov/media/178022/download
  196. International Society for Stem Cell Research. ISSCR Guidelines for Stem Cell Research and Clinical Translation. Version 1.2. International Society for Stem Cell Research. 2025. Accessed July 9, 2026. https://www.isscr.org/guidelines
  197. European Medicines Agency. Guideline on Human Cell- Based Medicinal Products. EMEA/CHMP/410869/2006. European Medicines Agency. 2008. Accessed July 9, 2026. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-human-cell-based-medicinal-products_ en.pdf
  198. Baker M. Reproducibility crisis: Blame it on the antibodies. Nature. 2015;521(7552):274-276. doi: 10.1038/521274a
  199. US Food and Drug Administration. Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use: Guidance for Industry and Food and Drug Administration Staff. US Food and Drug Administration. 2020. Accessed July 9, 2026. https://www.fda.gov/ regulatory-information/search-fda-guidance-documents/ regulatory-considerations-human-cells-tissues-and-cellular-and-tissue-based-products-minimal
  200. Jiao C, Karakaya OF, Dadgar N, et al. Mastering Organoid Growth: A Complete Guide to Overcoming Methodological Challenges. MedComm. 2026;7(1):e70571. doi: 10.1002/mco2.70571
  201. Wang Y, Qin J. Advances in human organoids-on-chips in biomedical research. Life Med. 2023;2(1):lnad007. doi: 10.1093/lifemedi/lnad007
  202. Park SE, Georgescu A, Huh D. Organoids-on-a-chip. Science. 2019;364(6444):960-965. doi: 10.1126/science.aaw7894
  203. Zhao Z, Chen X, Dowbaj AM, et al. Organoids. Nat Rev Methods Primers. 2022;2(1):94. doi: 10.1038/s43586-022-00174-y
  204. Xue Z, Yang R, Liu Y, Luo H. Organoid Models: Revolutionizing Disease Modeling and Personalized Therapeutics. Organoids. 2026;5(1):9. doi: 10.3390/organoids5010009
  205. Li Z, Yu D, Zhou C, et al. Engineering vascularised organoid-on-a-chip: strategies, advances and future perspectives. Biomater Transl. 2024;5(1):21-32. doi: 10.12336/biomatertransl.2024.01.003
  206. Kimura H, Nishikawa M, Kutsuzawa N, et al. Advancements in Microphysiological systems: Exploring organoids and organ-on-a-chip technologies in drug development -focus on pharmacokinetics related organs-. Drug Metab Pharmacokinet. 2025;60:101046. doi: 10.1016/j.dmpk.2024.101046
Next article in this issue
Share
Back to top
Organoid Research, Electronic ISSN: 3082-8503 Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept