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Volume 42 Issue 6
Jun.  2026
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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2026  >  42(6): 597-602
Wang MM,He YT,Xie QL,et al.Research advances on the application of skin appendage organoids in wound repair[J].Chin J Burns Wounds,2026,42(6):597-602.DOI: 10.3760/cma.j.cn501225-20260228-00092.
Citation: Wang MM,He YT,Xie QL,et al.Research advances on the application of skin appendage organoids in wound repair[J].Chin J Burns Wounds,2026,42(6):597-602.DOI: 10.3760/cma.j.cn501225-20260228-00092.
shu

Research advances on the application of skin appendage organoids in wound repair

doi: 10.3760/cma.j.cn501225-20260228-00092
  • 1.

    Key Laboratory of Biorheological Science and Technology of Ministry of Education111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400045, China

  • 2.

    Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing 400030, China

Funds:

National Key Research and Development Program of China 2023YFC2508200

General Program of National Natural Science Foundation of China 82373509, 82574005

National Natural Science Foundation of China Research Fund for International Young Scientists W2533206

Youth Science Foundation Project of National Natural Science Foundation of China 82504319

General Program of Natural Science Foundation of Chongqing CSTB2023NSCQ-MSX0866

Fundamental Research Funds for the Central Universities 2024CDJQYJCYJ-001

More Information
  • Corresponding author: Lei Mingxing, Email: mingxing@cqu.edu.cn
  • Received Date: 2026-02-28
    Available Online: 2026-06-18
    Abstract
  • Skin wounds are often accompanied by structural damage and functional loss of appendages such as hair follicles and sweat glands, which cannot be fully restored by conventional repair methods. The development of skin organoid technology provides a new avenue to overcome this bottleneck. This article reviews the developmental history of skin organoids and systematically elaborates on the strategies and applications of skin appendage organoids in promoting functional skin regeneration. Furthermore, it analyzes the critical role of vascular and neural integration in improving the quality of wound repair. Finally, the article summarizes the current challenges associated with technologies such as stem cell induction, three-dimensional bioprinting, microfluidics, organ-on-a-chip, and air-liquid interface culture, and provides perspectives on the clinical translation of skin appendage organoids.

     

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  • [1]
    SunBK,SiprashviliZ,KhavariPA.Advances in skin grafting and treatment of cutaneous wounds[J].Science,2014,346(6212):941-945.DOI: 10.1126/science.1253836.
    [2]
    RowethHG,BattinelliEM.Platelets and (lymph)angiogenesis[J].Cold Spring Harb Perspect Med,2023,13(1):a041174.DOI: 10.1101/cshperspect.a041174.
    [3]
    RheinwaldJG,GreenH.Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells[J].Cell,1975,6(3):331-343.DOI: 10.1016/s0092-8674(75)80001-8.
    [4]
    CoolenNA,VerkerkM,ReijnenL,et al.Culture of keratinocytes for transplantation without the need of feeder layer cells[J].Cell Transplant,2007,16(6):649-661.
    [5]
    GhioSC,BarbierMA,DoucetEJ,et al.A newly developed chemically defined serum-free medium suitable for human primary keratinocyte culture and tissue engineering applications[J].Int J Mol Sci,2023,24(3):1821.DOI: 10.3390/ijms24031821.
    [6]
    GuenouH,NissanX,LarcherF,et al.Human embryonic stem-cell derivatives for full reconstruction of the pluristratified epidermis: a preclinical study[J].Lancet,2009,374(9703):1745-1753.DOI: 10.1016/S0140-6736(09)61496-3.
    [7]
    MaJ,LiW,CaoR,et al.Application of an iPSC-derived organoid model for localized scleroderma therapy[J].Adv Sci (Weinh),2022,9(16):e2106075.DOI: 10.1002/advs.202106075.
    [8]
    BatailleA,LeschieraR,L'HérondelleK,et al.In vitro differentiation of human skin-derived cells into functional sensory neurons-like[J].Cells,2020,9(4):1000.DOI: 10.3390/cells9041000.
    [9]
    ZhouS,LiZ,LiX,et al.Crosstalk between endothelial cells and dermal papilla entails hair regeneration and angiogenesis during aging[J].J Adv Res,2025,70:339-353.DOI: 10.1016/j.jare.2024.05.006.
    [10]
    LiT,LiX,XiangX,et al.Regenerative hair pigmentation via skin organoids: adaptive patterning mediated by Collagen Ⅵ and Semaphorin 3C[J].Adv Sci (Weinh),2025,12(36):e02436.DOI: 10.1002/advs.202502436.
    [11]
    WangM,WangM,JiangJ,et al.THSD4 promotes hair growth by facilitating dermal papilla and hair matrix interactions[J].Theranostics,2025,15(8):3571-3588.DOI: 10.7150/thno.103221.
    [12]
    WuX,ZhongJ,JiangJ,et al.Endothelium-specific sensing of mechanical signals drives epidermal aging through coordinating retinoid metabolism[J].Theranostics,2025,15(14):7045-7063.DOI: 10.7150/thno.112299.
    [13]
    JiangJ,ShaoX,LiuW,et al.The mechano-chemical circuit in fibroblasts and dendritic cells drives basal cell proliferation in psoriasis[J].Cell Rep,2024,43(7):114513.DOI: 10.1016/j.celrep.2024.114513.
    [14]
    WangD,JiangJ,WangM,et al.Mitophagy promotes hair regeneration by activating glutathione metabolism[J].Research (Wash D C),2024,7:0433.DOI: 10.34133/research.0433.
    [15]
    LimX, NusseR. Wnt signaling in skin development, homeostasis, and disease[J]. Cold Spring Harb Perspect Biol, 2013,5(2):a008029. DOI: 10.1101/cshperspect.a008029.
    [16]
    AtitR,SgaierSK,MohamedOA,et al.Beta-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse[J].Dev Biol,2006,296(1):164-176.DOI: 10.1016/j.ydbio.2006.04.449.
    [17]
    SternCD.Neural induction: old problem, new findings, yet more questions[J].Development,2005,132(9):2007-2021.DOI: 10.1242/dev.01794.
    [18]
    ZhuXJ,LiuY,DaiZM,et al.BMP-FGF signaling axis mediates Wnt-induced epidermal stratification in developing mammalian skin[J].PLoS Genet,2014,10(10):e1004687.DOI: 10.1371/journal.pgen.1004687.
    [19]
    TaoB,LiX,HaoM,et al.Organoid-guided precision medicine: from bench to bedside[J].MedComm (2020),2025,6(5):e70195.DOI: 10.1002/mco2.70195.
    [20]
    ShwartzY, Gonzalez-CeleiroM, ChenCL, et al. Cell types promoting goosebumps form a niche to regulate hair follicle stem cells[J]. Cell, 2020, 182(3): 578-593.e19. DOI: 10.1016/j.cell.2020.06.031.
    [21]
    赵思远,李伟,孔维诗,等.皮肤类器官在创面修复中的应用研究进展[J].中华烧伤与创面修复杂志,2025,41(7):703-707.DOI: 10.3760/cma.j.cn501225-20240901-00323.
    [22]
    魏亚婷, 吴军. 创面修复中的皮肤组织再生研究进展[J].中华烧伤杂志,2021,37(7):670-674. DOI: 10.3760/cma.j.cn501120-20200604-00296.
    [23]
    SunJ,AhmedI,BrownJ,et al.The empowering influence of air-liquid interface culture on skin organoid hair follicle development[J/OL].Burns Trauma,2025,13:tkae070[2026-02-28]. https://pubmed.ncbi.nlm.nih.gov/39822647/.DOI: 10.1093/burnst/tkae070.
    [24]
    KageyamaT,ShimizuA,AnakamaR,et al.Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction[J].Sci Adv,2022,8(42):eadd4603.DOI: 10.1126/sciadv.add4603.
    [25]
    MaX,ZhuX,LvS,et al.3D bioprinting of prefabricated artificial skin with multicomponent hydrogel for skin and hair follicle regeneration[J].Theranostics,2025,15(7):2933-2950.DOI: 10.7150/thno.104854.
    [26]
    MaJ,QinC,WuJ,et al.3D multicellular micropatterning biomaterials for hair regeneration and vascularization[J].Mater Horiz,2023,10(9):3773-3784.DOI: 10.1039/d3mh00528c.
    [27]
    XieJ, YangQ, ZhangY, et al. The bioengineering of microspheric skin organoids and their application in drug screening[J]. Adv Sci (Weinh), 2025,12(22):e2416863. DOI: 10.1002/advs.202416863.
    [28]
    WebsterGF.Acne vulgaris[J].BMJ,2002,325(7362):475-479.
    [29]
    YinH,QiuZ,ZhuR,et al.Dysregulated lipidome of sebum in patients with atopic dermatitis[J].Allergy,2023,78(6):1524-1537.DOI: 10.1111/all.15569.
    [30]
    Al-ZaidT,VanderweilS,ZembowiczA,et al.Sebaceous gland loss and inflammation in scarring alopecia: a potential role in pathogenesis[J].J Am Acad Dermatol,2011,65(3):597-603.DOI: 10.1016/j.jaad.2010.09.774.
    [31]
    GruberR,SugarmanJL,CrumrineD,et al.Sebaceous gland, hair shaft, and epidermal barrier abnormalities in keratosis pilaris with and without filaggrin deficiency[J].Am J Pathol,2015,185(4):1012-1021.DOI: 10.1016/j.ajpath.2014.12.012.
    [32]
    ShiVY,LeoM,HassounL,et al.Role of sebaceous glands in inflammatory dermatoses[J].J Am Acad Dermatol,2015,73(5):856-863.DOI: 10.1016/j.jaad.2015.08.015.
    [33]
    SnippertHJ,HaegebarthA,KasperM,et al.Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin[J].Science,2010,327(5971):1385-1389.DOI: 10.1126/science.1184733.
    [34]
    BlanpainC.Stem cells: skin regeneration and repair[J].Nature,2010,464(7289):686-687.DOI: 10.1038/464686a.
    [35]
    ZhaoH,QiaoJ,ZhangS,et al.GPR39 marks specific cells within the sebaceous gland and contributes to skin wound healing[J].Sci Rep,2015,5:7913.DOI: 10.1038/srep07913.
    [36]
    TaoK, BaiX, JiP, et al. A composite of hepatocyte growth factor- and 5α-dihydrotestosterone-gelatin microspheres with adipose-derived stem cells enhances wound healing[J]. Skin Pharmacol Physiol, 2022, 35(4): 206-214. DOI: 10.1159/000524188.
    [37]
    WangX, WangX, LiuJ, et al. Hair follicle and sebaceous gland de novo regeneration with cultured epidermal stem cells and skin-derived precursors[J]. Stem Cells Transl Med, 2016,5(12):1695-1706. DOI: 10.5966/sctm.2015-0397.
    [38]
    XiongM, YangX, ShiZ, et al. Programmable artificial skins accomplish antiscar healing with multiple appendage regeneration[J]. Adv Mater, 2024,36(50):e2407322. DOI: 10.1002/adma.202407322.
    [39]
    LiuJ,XuD,YanJ,et al.A novel H-tert immortalized human sebaceous gland cell line (XL-i-20) for the investigation of photodynamic therapy[J].Photodiagnosis Photodyn Ther,2024,48:104238.DOI: 10.1016/j.pdpdt.2024.104238.
    [40]
    PhanMAT, MadiganMC, StapletonF,et al.Human meibomian gland epithelial cell culture models: current progress, challenges, and future directions[J].Ocul Surf,2022,23:96-113.DOI: 10.1016/j.jtos.2021.11.012.
    [41]
    XiangJ,ChenH,ZhangH,et al.Restoring sweat gland function in mice using regenerative sweat gland cells derived from chemically reprogrammed human epidermal keratinocytes[J].Sci Bull (Beijing),2024,69(24):3908-3924.DOI: 10.1016/j.scib.2024.11.003.
    [42]
    SunX, XiangJ, ChenR, et al. Sweat gland organoids originating from reprogrammed epidermal keratinocytes functionally recapitulated damaged skin[J]. Adv Sci (Weinh), 2021,8(22):e2103079. DOI: 10.1002/advs.202103079.
    [43]
    DiaoJ,LiuJ,WangS,et al.Sweat gland organoids contribute to cutaneous wound healing and sweat gland regeneration[J].Cell Death Dis,2019,10(3):238.DOI: 10.1038/s41419-019-1485-5.
    [44]
    ShafieeA,SunJ,AhmedIA,et al.Development of physiologically relevant skin organoids from human induced pluripotent stem cells[J].Small,2024,20(16):e2304879.DOI: 10.1002/smll.202304879.
    [45]
    YaoB,WangR,WangY,et al.Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration[J].Sci Adv,2020,6(10):eaaz1094.DOI: 10.1126/sciadv.aaz1094.
    [46]
    YuanX,DuanX,Enhejirigala,et al.Reciprocal interaction between vascular niche and sweat gland promotes sweat gland regeneration[J].Bioact Mater,2023,21:340-357.DOI: 10.1016/j.bioactmat.2022.08.021.
    [47]
    Tiruvannamalai AnnamalaiR, RiojaAY, PutnamAJ, et al. Vascular network formation by human microvascular endothelial cells in modular fibrin microtissues[J]. ACS Biomater Sci Eng, 2016,2(11):1914-1925. DOI: 10.1021/acsbiomaterials.6b00274.
    [48]
    GongL,ZhangY,ZhuY,et al.Rapid generation of functional vascular organoids via simultaneous transcription factor activation of endothelial and mural lineages[J].Cell Stem Cell,2025,32(8):1200-1217.e6.DOI: 10.1016/j.stem.2025.05.014.
    [49]
    LeeD,ParkC,LeeH,et al.ER71 acts downstream of BMP, Notch, and Wnt signaling in blood and vessel progenitor specification[J].Cell Stem Cell,2008,2(5):497-507.DOI: 10.1016/j.stem.2008.03.008.
    [50]
    MostinaM,SunJ,SimSL,et al.Coordinated development of immune cell populations in vascularized skin organoids from human induced pluripotent stem cells[J].Adv Healthc Mater,2025,14(31):e02108.DOI: 10.1002/adhm.202502108.
    [51]
    Frenz-WiessnerS,FairleySD,BuserM,et al.Generation of complex bone marrow organoids from human induced pluripotent stem cells[J].Nat Methods,2024,21(5):868-881.DOI: 10.1038/s41592-024-02172-2.
    [52]
    SaikiN,NioY,YoneyamaY,et al.Self-organization of sinusoidal vessels in pluripotent stem cell-derived human liver bud organoids[J].Nat Biomed Eng,2025,9(11):1869-1885.DOI: 10.1038/s41551-025-01416-6.
    [53]
    WimmerRA,LeopoldiA,AichingerM,et al.Generation of blood vessel organoids from human pluripotent stem cells[J].Nat Protoc,2019,14(11):3082-3100.DOI: 10.1038/s41596-019-0213-z.
    [54]
    WangK,LanX,ChenJ,et al.One-step coaxial 3D printing of pre-vascularized skin organoid models with ADSC microspheres for enhanced wound healing[J].Adv Sci (Weinh),2026,13(9):e17409.DOI: 10.1002/advs.202517409.
    [55]
    Translational Research InstituteUQ scientists grow living skin in world first2025-08-212026-02-28https://news.uq.edu.au/2025-08-uq-scientists-grow-living-skin-world-first

    Translational Research Institute. UQ scientists grow living skin in world first[EB/OL]. (2025-08-21) [2026-02-28]. https://news.uq.edu.au/2025-08-uq-scientists-grow-living-skin-world-first.
    [56]
    RashidanK, AyadilordM, HazratiA, et al. Immune and immune-integrated organoids as nextgeneration platforms for disease modeling[J]. MedComm (2020), 2025,6(12):e70531. DOI: 10.1002/mco2.70531.
    [57]
    LakehB,ShafieeA.Advancing dermatology with skin equivalents and organoids in pathophysiology and drug testing[J].Acta Biomater,2025,207:120-130.DOI: 10.1016/j.actbio.2025.10.008.
    [58]
    BrownellI,GuevaraE,BaiCB,et al.Nerve-derived sonic hedgehog defines a niche for hair follicle stem cells capable of becoming epidermal stem cells[J].Cell Stem Cell,2011,8(5):552-565.DOI: 10.1016/j.stem.2011.02.021.
    [59]
    ZimmermanA,BaiL,GintyDD.The gentle touch receptors of mammalian skin[J].Science,2014,346(6212):950-954.DOI: 10.1126/science.1254229.
    [60]
    JieJ,JuJ,WangZ,et al.Organoid-like neurovascular spheroids promote the recovery of hypoxic-ischemic skin flaps through the activation of autophagy[J].Adv Healthc Mater,2025,14(15):e2405154.DOI: 10.1002/adhm.202405154.
    [61]
    KiyaK,KuboT.Neurovascular interactions in skin wound healing[J].Neurochem Int,2019,125:144-150.DOI: 10.1016/j.neuint.2019.02.014.
    [62]
    KistemakerL,van BodegravenEJ,deVries HE,et al.Vascularized human brain organoids: current possibilities and prospects[J].Trends Biotechnol,2025,43(6):1275-1285.DOI: 10.1016/j.tibtech.2024.11.021.
    [63]
    KolterJ,DöringCL,SaroutS,et al.Sensory neurons shape local macrophage identity via TGF-β signaling[J].Immunity,2025,58(10):2556-2573.e8.DOI: 10.1016/j.immuni.2025.08.004.
    [64]
    ZhuZ,ZhangX,HaoH,et al.Exosomes derived from umbilical cord mesenchymal stem cells treat cutaneous nerve damage and promote wound healing[J].Front Cell Neurosci,2022,16:913009.DOI: 10.3389/fncel.2022.913009.
    [65]
    LiuJ,LinZ,WuH,et al.Dual-regulation biomimetic composite nerve scaffold with oriented structure and conductive function for skin peripheral nerve injury repair[J].Colloids Surf B Biointerfaces,2025,253:114768.DOI: 10.1016/j.colsurfb.2025.114768.
    [66]
    WangS,LiuZ,ChenC,et al.Flexible amorphous silicon radial junction patches promote skin regeneration by offering wireless photoelectric neuromodulation[J].ACS Nano,2025,19(20):18996-19008.DOI: 10.1021/acsnano.4c16337.
    [67]
    KajtezJ,LaurinK,NilssonF,et al.Three-dimensional cell-cell interactions promote direct reprogramming of patient fibroblasts into functional and transplantable neurons[J].Sci Adv,2025,11(23):eadq7855.DOI: 10.1126/sciadv.adq7855.
    [68]
    NishijimaT,OkuyamaK,ShibataS,et al.Novel artificial nerve transplantation of human iPSC-derived neurite bundles enhanced nerve regeneration after peripheral nerve injury[J].Inflamm Regen,2024,44(1):6.DOI: 10.1186/s41232-024-00319-4.
    [69]
    PowellRA, AtkinsonEA, SmithPO, et al. Engineered neural tissue (EngNT) containing human iPSC-derived schwann cell precursors promotes axon growth in a rat model of peripheral nerve injury[J]. Bioengineering (Basel), 2025,12(9):904.DOI: 10.3390/bioengineering12090904.
    [70]
    National Institutes of HealthNIH establishes nation's first dedicated organoid development center to reduce reliance on animal modeling2025-09-252026-02-28https://www.nih.gov/news-events/news-releases/nih-establishes-nations-first-dedicated-organoid-development-center-reduce-reliance-animal-modeling

    National Institutes of Health. NIH establishes nation's first dedicated organoid development center to reduce reliance on animal modeling[EB/OL]. (2025-09-25)[2026-02-28]. https://www.nih.gov/news-events/news-releases/nih-establishes-nations-first-dedicated-organoid-development-center-reduce-reliance-animal-modeling.
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