AccScience Publishing / OR / Online First / DOI: 10.36922/OR026060009
REVIEW ARTICLE

Progress and perspectives on hydrogel-assisted skin organoids

Yulian Zheng1 Zhiling Luo2 Yongli Li1 Xinyi Huang1 Yushan He1 Hengshu Zhang1 Yi Zhu3 Russell R. Reid3,4 Tong-Chuan He3* Lu Chen1*
Show Less
1 Department of Burn and Plastic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
2 Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
3 Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States of America
4 Laboratory of Craniofacial Biology and Development, Section of Plastic and Reconstructive Surgery, Department of Surgery, The University of Chicago Medical Center, Chicago, IL, United States of America
Received: 8 February 2026 | Revised: 10 March 2026 | Accepted: 13 March 2026 | Published online: 26 May 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/ )
Abstract

Skin organoids offer a powerful in vitro platform for modeling human skin physiology, disease mechanisms, and regenerative processes. However, faithfully recapitulating the multilayered architecture of skin, diverse appendages, and integrated vascular– neural networks remains a major challenge. As key extracellular matrix mimetics, hydrogels have emerged as central enablers in advancing skin organoid engineering by complementing passive self-organization with programmable biofabrication strategies. This review summarizes recent progress in hydrogel-assisted skin organoid engineering, highlighting how these systems enable the reconstruction of layered skin architectures, support the morphogenesis of skin appendages, and facilitate the integration of vascular and neural components, thereby progressively improving the structural and functional fidelity of skin organoids. These developments position hydrogel-based platforms as essential tools for advancing next-generation skin organoid models. By enabling more precise control over the microenvironment and tissue organization, hydrogel-assisted strategies are expected to accelerate the development of physiologically relevant skin organoids and expand their applications in regenerative medicine, drug discovery, and the study of complex skin disorders.

Graphical abstract
Keywords
Skin organoids
Hydrogels
Skin tissue engineering
3D bioprinting
Extracellular matrix
Funding
This work was supported in part by the National Natural Science Foundation of China (82202456), the Scientific and Technological Research Program of Chongqing Municipal Education Commission (KJQN202400424), the China Postdoctoral Science Foundation Special Program (2025T180555), the Young Top Talent Program of the First Affiliated Hospital of Chongqing Medical University (ZYRC2022-01), the Chongqing Municipal Special Postdoctoral Science Foundation (2023CQBSHTB3105), the Young Top Talent Program in Medicine, Chongqing Municipality (YXQN202467), and the China Postdoctoral Science Foundation General Program (2024MD754019).
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Gravitz L. Skin. Nature. 2018;563(7732):S83-S83. doi: 10.1038/d41586-018-07428-4
  2. Arda O, Göksügür N, Tüzün Y. Basic histological structure and functions of facial skin. Clin Dermatol. 2014;32(1):3-13. doi: 10.1016/j.clindermatol.2013.05.021
  3. Takeo M, Lee W, Ito M. Wound healing and skin regeneration. Cold Spring Harb Perspect Med. 2015;5(1):a023267. doi: 10.1101/cshperspect.a023267
  4. Nicolaou A, Kendall AC. Bioactive lipids in the skin barrier mediate its functionality in health and disease. Pharmacol Ther. 2024;260:108681. doi: 10.1016/j.pharmthera.2024.108681
  5. Li W, Liang Y, Tan X, et al. Self-powered microneedle patch with synergistic mild microwave thermal therapy for scarless healing of infected diabetic wound. ACS Appl Mater Interfaces. 2025;17(46):62936-62956. doi: 10.1021/acsami.5c14924
  6. Ullah S, Mansoor S, Ayub A, et al. An update on stem cells applications in burn wound healing. Tissue Cell. 2021;72:101527. doi: 10.1016/j.tice.2021.101527
  7. Jacobi U, Kaiser M, Toll R, et al. Porcine ear skin: an in vitro model for human skin. Skin Res Technol. 2007;13(1):19-24. doi: 10.1111/j.1600-0846.2006.00179.x
  8. Bartek MJ, LaBudde JA, Maibach HI. Skin permeability in vivo: comparison in rat, rabbit, pig and man. J Invest Dermatol. 1972;58(3):114-123. doi: 10.1111/1523-1747.ep12538909
  9. Schmook FP, Meingassner JG, Billich A. Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption. Int J Pharm. 2001;215(1-2):51-56. doi: 10.1016/s0378-5173(00)00665-7
  10. Yan HHN, Chan AS, Lai FP, Leung SY. Organoid cultures for cancer modeling. Cell Stem Cell. 2023;30(7):917-937. doi: 10.1016/j.stem.2023.05.012
  11. Ali M, Pr AK, Yoo JJ, Zahran F, Atala A, Lee SJ. A photo-crosslinkable kidney ECM-derived bioink accelerates renal tissue formation. Adv Healthc Mater. 2019;8(7):e1800992. doi: 10.1002/adhm.201800992
  12. Hu N, Shi JX, Chen C, et al. Constructing organoid-brain-computer interfaces for neurofunctional repair after brain injury. Nat Commun. 2024;15(1):9580. doi: 10.1038/s41467-024-53858-2
  13. Klotz BJ, Oosterhoff LA, Utomo L, et al. A versatile biosynthetic hydrogel platform for engineering of tissue analogues. Adv Healthc Mater. 2019;8(19):e1900979. doi: 10.1002/adhm.201900979
  14. Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009;459(7244):262-265. doi: 10.1038/nature07935
  15. 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
  16. 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
  17. Lee J, Sutani A, Kaneko R, et al. In vitro generation of functional murine heart organoids via FGF4 and extracellular matrix. Nat Commun. 2020;11(1):4283. doi: 10.1038/s41467-020-18031-5
  18. Lei M, Jiang J, Wang M, et al. Epidermal-dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures. NPJ Regen Med. 2023;8(1):65. doi: 10.1038/s41536-023-00340-0
  19. Weng T, Wu P, Zhang W, et al. Regeneration of skin appendages and nerves: current status and further challenges. J Transl Med. 2020;18(1):53. doi: 10.1186/s12967-020-02248-5
  20. Chen L, Xing Q, Zhai Q, et al. Pre-vascularization enhances therapeutic effects of human mesenchymal stem cell sheets in full thickness skin wound repair. Theranostics. 2017;7(1):117- 131. doi: 10.7150/thno.17031
  21. Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010;123(24):4195-4200. doi: 10.1242/jcs.023820
  22. Caliari SR, Burdick JA. A practical guide to hydrogels for cell culture. Nat Methods. 2016;13(5):405-414. doi: 10.1038/nmeth.3839
  23. Guvendiren M, Burdick JA. Engineering synthetic hydrogel microenvironments to instruct stem cells. Curr Opin Biotechnol. 2013;24(5):841-846. doi: 10.1016/j.copbio.2013.03.009
  24. Chen X, Feng Y, Zhang P, Ni Z, Xue Y, Liu J. Hydrogel fibers-based biointerfacing. Adv Mater. 2025;37(4):e2413476. doi: 10.1002/adma.202413476
  25. 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
  26. Cubo N, Garcia M, del Cañizo 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
  27. Ganguly S, Wulff D, Phan CM, Jones LW, Tang XS. Injectable and 3D extrusion printable hydrophilic silicone-based hydrogels for controlled ocular delivery of ophthalmic drugs. ACS Appl Bio Mater. 2024;7(9):6286-6296. doi: 10.1021/acsabm.4c00901
  28. Griffin DR, Weaver WM, Scumpia PO, Di Carlo D, Segura T. Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks. Nat Mater. 2015;14(7):737-744. doi: 10.1038/nmat4294
  29. 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
  30. Viswanathan P, Guvendiren M, Chua W, et al. Mimicking the topography of the epidermal–dermal interface with elastomer substrates. Integr Biol. 2016;8(1):21-29. doi: 10.1039/c5ib00238a
  31. Trappmann B, Gautrot JE, Connelly JT, et al. Extracellular-matrix tethering regulates stem-cell fate. Nat Mater. 2012;11(7):642-649. doi: 10.1038/nmat3339
  32. Wisdom EC, Aduba DC, 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
  33. Song W, Yao B, Zhu D, et al. 3D-bioprinted microenvironments for sweat gland regeneration. Burns Trauma. 2022;10:tkab044. doi: 10.1093/burnst/tkab044
  34. 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
  35. Bertassoni LE, Cecconi M, Manoharan V, et al. Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip. 2014;14(13):2202- 2211. doi: 10.1039/c4lc00030g
  36. Bellantoni D, Casale C, Mazio C, Urciuolo F, Imparato G, Netti PA. Development of an innervated human skin equivalent to model nociceptive circuitry in vitro. Biomaterials. 2026;328:123808. doi: 10.1016/j.biomaterials.2025.123808
  37. Das P, Ganguly S, Saravanan A, et al. Naturally derived carbon dots in situ confined self-healing and breathable hydrogel monolith for anomalous diffusion-driven phytomedicine release. ACS Appl Bio Mater. 2022;5(12):5617-5633. doi: 10.1021/acsabm.2c00664
  38. Morasso MI, Tomic‐Canic M. Epidermal stem cells: the cradle of epidermal determination, differentiation and wound healing. Biol Cell. 2012;97(3):173-183. doi: 10.1042/bc20040098
  39. Frankart A, Malaisse J, De Vuyst E, Minner F, de Rouvroit CL, Poumay Y. Epidermal morphogenesis during progressive in vitro 3D reconstruction at the air–liquid interface. Exp Dermatol. 2012;21(11):871-875. doi: 10.1111/exd.12020
  40. 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
  41. 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
  42. Kaur S, Kaur I, Rawal P, Tripathi DM, Vasudevan A. Non-matrigel scaffolds for organoid cultures. Cancer Lett. 2021;504:58-66. doi: 10.1016/j.canlet.2021.01.025
  43. 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
  44. 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
  45. Woodley DT. Distinct fibroblasts in the papillary and reticular dermis: implications for wound healing. Dermatol Clin. 2017;35(1):95-100. doi: 10.1016/j.det.2016.07.004
  46. Zhou M, Ulijn RV, Gough JE. Extracellular matrix formation in self-assembled minimalistic bioactive hydrogels based on aromatic peptide amphiphiles. J Tissue Eng. 2014;5:2041731414531593. doi: 10.1177/2041731414531593
  47. Guo Y, Bian Z, Xu Q, et al. Novel tissue-engineered skin equivalent from recombinant human collagen hydrogel and fibroblasts facilitated full-thickness skin defect repair in a mouse model. Mater Sci Eng C Mater Biol Appl. 2021;130:112469. doi: 10.1016/j.msec.2021.112469
  48. RI RI, do Amaral R, Reis RL, Marques AP, Murphy CM, O’Brien FJ. 3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regeneration. Polymers (Basel). 2021;13(15):2510. doi: 10.3390/polym13152510
  49. Fuchs E. Epithelial Skin Biology. In: Essays on Developmental Biology, Part A (Current Topics in Developmental Biology). Elsevier; 2016:357-374. doi: 10.1016/bs.ctdb.2015.11.033
  50. Baker P, Huang C, Radi R, Moll SB, Jules E, Arbiser JL. Skin barrier function: the interplay of physical, chemical, and immunologic properties. Cells. 2023;12(23):2745. doi: 10.3390/cells12232745
  51. 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
  52. Jorgensen AM, Varkey M, Gorkun A, et al. Bioprinted skin recapitulates normal collagen remodeling in full-thickness wounds. Tissue Eng Part A. 2020;26(9-10):512-526. doi: 10.1089/ten.TEA.2019.0319
  53. Montero A, Quílez C, Valencia L, Girón P, Jorcano JL, Velasco D. Effect of fibrin concentration on the in vitro production of dermo-epidermal equivalents. Int J Mol Sci. 2021;22(13):6746. doi: 10.3390/ijms22136746
  54. Li X, Wang C, Xiong Q, et al. A photocurable and thermocurable composite hydrogel and the application in a contraction resistant full-thickness skin model. Biofabrication. 2024;17(1):015043. doi: 10.1088/1758-5090/ad905e
  55. Bacakova M, Pajorova J, Broz A, et al. A two-layer skin construct consisting of a collagen hydrogel reinforced by a fibrin-coated polylactide nanofibrous membrane. Int J Nanomedicine. 2019;14:5033-5050. doi: 10.2147/ijn.S200782
  56. Blackstone BN, Malara MM, Baumann ME, McFarland KL, Supp DM, Powell HM. Fractional CO(2) laser micropatterning of cell-seeded electrospun collagen scaffolds enables rete ridge formation in 3D engineered skin. Acta Biomater. 2020;102:287-297. doi: 10.1016/j.actbio.2019.11.051
  57. Roig-Rosello E, Rousselle P. The human epidermal basement membrane: a shaped and cell instructive platform that aging slowly alters. Biomolecules. 2020;10(12):1607. doi: 10.3390/biom10121607
  58. Shen Z, Cao Y, Li M, et al. Construction of tissue-engineered skin with rete ridges using co-network hydrogels of gelatin methacrylated and poly(ethylene glycol) diacrylate. Mater Sci Eng C Mater Biol Appl. 2021;129:112360. doi: 10.1016/j.msec.2021.112360
  59. Shen Z, Liu Z, Sun L, et al. Constructing epidermal rete ridges using a composite hydrogel to enhance multiple signaling pathways for the maintenance of epidermal stem cell niche. Acta Biomater. 2023;169:273-288. doi: 10.1016/j.actbio.2023.07.037
  60. 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 (Weinh). 2025;12(22):e2416863. doi: 10.1002/advs.202416863
  61. 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
  62. Wang M, Luo Y, Wang T, et al. Artificial skin perception. Adv Mater. 2021;33(19):e2003014. doi: 10.1002/adma.202003014
  63. Sutterby E, Thurgood P, Baratchi S, Khoshmanesh K, Pirogova E. Microfluidic skin-on-a-chip models: toward biomimetic artificial skin. Small. 2020;16(39):e2002515. doi: 10.1002/smll.202002515
  64. Cao X, Lu M, Li N, Cai L, Wang Y, Zhao Y. Emerging biomedical engineering strategies for hair follicle regeneration. Bioact Mater. 2025;53:84-113. doi: 10.1016/j.bioactmat.2025.06.051
  65. Zhu L, Yuhan J, Yu H, Zhang B, Huang K, Zhu L. Decellularized extracellular matrix for remodeling bioengineering organoid’s microenvironment. Small. 2023;19(25):e2207752. doi: 10.1002/smll.202207752
  66. Kageyama T, Miyata H, Seo J, Nanmo A, Fukuda J. In vitro hair follicle growth model for drug testing. Sci Rep. 2023;13(1):4847. doi: 10.1038/s41598-023-31842-y
  67. Abreu CM, Gasperini L, Lago MEL, Reis RL, Marques AP. Microscopy-guided laser ablation for the creation of complex skin models with folliculoid appendages. Bioeng Transl Med. 2021;6(2):e10195. doi: 10.1002/btm2.10195
  68. 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
  69. Chen H, Ma X, Zhang M, Liu Z. Injectable and biofunctionalized fibrin hydrogels co-embedded with stem cells induce hair follicle genesis. Regen Biomater. 2023;10:rbac086. doi: 10.1093/rb/rbac086
  70. Lin BJ, Wang J, Miao Y, et al. Cytokine loaded layer-by-layer ultrathin matrices to deliver single dermal papilla cells for spot-by-spot hair follicle regeneration. J Mater Chem B. 2016;4(3):489-504. doi: 10.1039/c5tb02265g
  71. 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
  72. 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
  73. Zheng B, Yang L, Feng S, et al. Organoid-loaded cryomicroneedles for biomimic hair regeneration. Adv Funct Mater. 2024;34(3). doi: 10.1002/adfm.202304950
  74. Liu Y, Gao H, Chen H, et al. Sebaceous gland organoid engineering. Burns Trauma. 2024;12:tkae003. doi: 10.1093/burnst/tkae003
  75. Yoshida GJ, Saya H. Three-dimensional culture of sebaceous gland cells revealing the role of prostaglandin E2-induced activation of canonical Wnt signaling. Biochem Biophys Res Commun. 2013;438(4):640-646. doi: 10.1016/j.bbrc.2013.07.129
  76. Liu J, Xu D, Yan J, et al. A novel H‑tert immortalized human sebaceous gland cell line (XL-i-20) for the investigation of photodynamic therapy. Photodiagnosis Photodyn Ther. 2024;48. doi: 10.1016/j.pdpdt.2024.104238
  77. 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
  78. Cui CY, Schlessinger D. Eccrine sweat gland development and sweat secretion. Exp Dermatol. 2015;24(9):644-650. doi: 10.1111/exd.12773
  79. Lin Y, Chen L, Zhang M, et al. Eccrine sweat gland and its regeneration: current status and future directions. Front Cell Dev Biol. 2021;9:667765. doi: 10.3389/fcell.2021.667765
  80. 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
  81. 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
  82. Zhang C, Chen Y, Fu X. Sweat gland regeneration after burn injury: is stem cell therapy a new hope? Cytotherapy. 2015;17(5):526-535. doi: 10.1016/j.jcyt.2014.10.016
  83. 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
  84. Yao B, Wang R, Wang Y, et al. Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration. Sci Adv. 2020;6(10):eaaz1094. doi: 10.1126/sciadv.aaz1094
  85. Wang K, Lan X, Chen J, et al. One-step coaxial 3D printing of pre-vascularized skin organoid models with ADSC microspheres for enhanced wound healing. Adv Sci. 2025:e17409. doi: 10.1002/advs.202517409
  86. Wang Y, Kankala RK, Ou C, Chen A, Yang Z. Advances in hydrogel-based vascularized tissues for tissue repair and drug screening. Bioact Mater. 2022;9:198-220. doi: 10.1016/j.bioactmat.2021.07.005
  87. Schechner JS, Nath AK, Zheng L, et al. In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. Proc Natl Acad Sci USA. 2000;97(16):9191-9196. doi: 10.1073/pnas.150242297
  88. Strobel HA, Gerton T, Hoying JB. Vascularized adipocyte organoid model using isolated human microvessel fragments. Biofabrication. 2021;13(3):035022. doi: 10.1088/1758-5090/abe187
  89. Zhou F, Hong Y, Liang R, et al. Rapid printing of bio-inspired 3D tissue constructs for skin regeneration. Biomaterials. 2020;258:120287. doi: 10.1016/j.biomaterials.2020.120287
  90. Ma X, Zhu X, Lv S, et al. 3D bioprinting of prefabricated artificial skin with multicomponent hydrogel for skin and hair follicle regeneration. Theranostics. 2025;15(7):2933- 2950. doi: 10.7150/thno.104854
  91. 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
  92. Laverdet B, Danigo A, Girard D, Magy L, Demiot C, Desmoulière A. Skin innervation: important roles during normal and pathological cutaneous repair. Histol Histopathol. 2015;30(8):875-892. doi: 10.14670/hh-11-610
  93. Ahn J, Ohk K, Won J, et al. Modeling of three-dimensional innervated epidermal like-layer in a microfluidic chip-based coculture system. Nat Commun. 2023;14(1):1488. doi: 10.1038/s41467-023-37187-4
  94. Muller Q, Beaudet MJ, De Serres-Bérard T, Bellenfant S, Flacher V, Berthod F. Development of an innervated tissue-engineered skin with human sensory neurons and Schwann cells differentiated from iPS cells. Acta Biomater. 2018;82:93- 101. doi: 10.1016/j.actbio.2018.10.011
  95. Jie J, Ju J, Wang Z, Chen J, Wu LP, Sun J. Organoid-like neurovascular spheroids promote the recovery of hypoxic-ischemic skin flaps through the activation of autophagy. Adv Healthc Mater. 2025;14(15):e2405154. doi: 10.1002/adhm.202405154
  96. 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
  97. Yi SA, Zhang Y, Rathnam C, Pongkulapa T, Lee KB. Bioengineering approaches for the advanced organoid research. Adv Mater. 2021;33(45):e2007949. doi: 10.1002/adma.202007949
  98. Hsiung N, Ju Y, Yang K, Yang P, Zeng W, Zhao H, et al. Organoid-based tissue engineering for advanced tissue repair and reconstruction. Mater Today Bio. 2025;33:102093. doi: 10.1016/j.mtbio.2025.102093
  99. Aisenbrey EA, Murphy WL. Synthetic alternatives to Matrigel. Nat Rev Mater. 2020;5(7):539-551. doi: 10.1038/s41578-020-0199-8
  100. Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254-271. doi: 10.1016/j.biomaterials.2015.08.045
  101. Silver FH, Siperko LM, Seehra GP. Mechanobiology of force transduction in dermal tissue. Skin Res Technol. 2003;9(1):3- 23. doi: 10.1034/j.1600-0846.2003.00358.x
  102. Annabi N, Nichol JW, Zhong X, Ji C, Koshy S, Khademhosseini A, et al. Controlling the porosity and microarchitecture of hydrogels for tissue engineering. Tissue Eng Part B Rev. 2010;16(4):371-383. doi: 10.1089/ten.TEB.2009.0639
  103. Abaci HE, Guo Z, Coffman A, Gillette B, Lee WH, Sia SK, et al. Human skin constructs with spatially controlled vasculature using primary and iPSC-derived endothelial cells. Adv Healthc Mater. 2016;5(14):1800-1807. doi: 10.1002/adhm.201500936
  104. Wimmer RA, Leopoldi A, Aichinger M, Wick N, Hantusch B, Novatchkova 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
  105. Kawara S, Cunningham B, Bezer J, Kc N, Zhu J, Tang MX, et al. Capillary-scale hydrogel microchannel networks by wire templating. Small. 2023;19(42):e2301163. doi: 10.1002/smll.202301163
  106. Randall MJ, Jüngel A, Rimann M, Wuertz-Kozak K. Advances in the biofabrication of 3D skin in vitro: healthy and pathological models. Front Bioeng Biotechnol. 2018;6:154. doi: 10.3389/fbioe.2018.00154
  107. Böttcher P, Steinmeyer L, Stark H, Breitkreutz J, Mewes KR. Integration of MUTZ-Langerhans cells into a 3D full-thickness skin equivalent and influences of serum reduction and undefined medium supplements on differentiation. Toxicol In Vitro. 2025;102:105948. doi: 10.1016/j.tiv.2024.105948
  108. Hollstein MM, Nüsken M, Hahn KK, Mewes KR, Teusch N, Dasari P, et al. Generating immunocompetent 3-dimensional full-thickness models of human skin. J Invest Dermatol. 2026;146(1):30-39.e3. doi: 10.1016/j.jid.2025.10.592
  109. Hsu YC, Li L, Fuchs E. Transit-amplifying cells orchestrate stem cell activity and tissue regeneration. Cell. 2014;157(4):935-949. doi: 10.1016/j.cell.2014.02.057
  110. Lu CP, Polak L, Rocha AS, Pasolli HA, Chen SC, Sharma N, et al. Identification of stem cell populations in sweat glands and ducts reveals roles in homeostasis and wound repair. Cell. 2012;150(1):136-150. doi: 10.1016/j.cell.2012.04.045
  111. Madhusudanan P, Raju G, Shankarappa S. Hydrogel systems and their role in neural tissue engineering. J R Soc Interface. 2020;17(162):20190505. doi: 10.1098/rsif.2019.0505
  112. Li Z, Lu J, Ji T, Xue Y, Zhao L, Zhao K, et al. Self-healing hydrogel bioelectronics. Adv Mater. 2024;36(21):e2306350. doi: 10.1002/adma.202306350
  113. Fan L, Liu C, Chen X, Zheng L, Zou Y, Wen H, et al. Exosomes-loaded electroconductive hydrogel synergistically promotes tissue repair after spinal cord injury via immunoregulation and enhancement of myelinated axon growth. Adv Sci. 2022;9(13):e2105586. doi: 10.1002/advs.202105586
  114. Zhu Y, Huang R, Yu L, Liu Z, Liu Y, Fan W, et al. Engineered thoracic spinal cord organoids for transplantation after spinal cord injury. Nat Biomed Eng. 2025. doi: 10.1038/s41551-025-01549-8
  115. Lin JY, Fisher DE. Melanocyte biology and skin pigmentation. Nature. 2007;445(7130):843-850. doi: 10.1038/nature05660
  116. Haass NK, Smalley KS, Li L, Herlyn M. Adhesion, migration and communication in melanocytes and melanoma. Pigment Cell Res. 2005;18(3):150-159. doi: 10.1111/j.1600-0749.2005.00235.x
  117. El Ghalbzouri A, Jonkman MF, Dijkman R, Ponec M. Basement membrane reconstruction in human skin equivalents is regulated by fibroblasts and/or exogenously activated keratinocytes. J Invest Dermatol. 2005;124(1):79- 86. doi: 10.1111/j.0022-202X.2004.23549.x
  118. Belkaid Y, Segre JA. Dialogue between skin microbiota and immunity. Science. 2014;346(6212):954-959. Volume x Issue x (2026) 18 doi: 10.36922/OR026060009 doi: 10.1126/science.1260144
  119. Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol. 2018;16(3):143-155. doi: 10.1038/nrmicro.2017.157
Share
Back to top
Organoid Research, Electronic ISSN: 3082-8503 Published by AccScience Publishing