Volume 42 Issue 6
Jun.  2026
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Wang GC,Su JC.Organoid-based strategies and challenges in tissue regeneration[J].Chin J Burns Wounds,2026,42(6):514-521.DOI: 10.3760/cma.j.cn501225-20260119-00033.
Citation: Wang GC,Su JC.Organoid-based strategies and challenges in tissue regeneration[J].Chin J Burns Wounds,2026,42(6):514-521.DOI: 10.3760/cma.j.cn501225-20260119-00033.

Organoid-based strategies and challenges in tissue regeneration

doi: 10.3760/cma.j.cn501225-20260119-00033
Funds:

Key Program of National Natural Science Foundation of China 82230071, 82530072

Shanghai Municipal Demonstration Project for Innovative Medical Device Application 23SHS05700

Shanghai Disruptive Technology Innovation Project 25DIPA00400

Shanghai Municipal Health Commission New Medical Technology Research and Translation Seed Program 2024ZZ1001

More Information
  • Tissue regenerative medicine aims to repair or replace tissue and organs that have lost function due to disease, trauma, or aging, and the emergence of organoid technology has provided a new avenue for this field. Organoids are self-organized structures formed under three-dimensional culture conditions. They can recapitulate the structure and function of native organs, demonstrating unique advantages in disease modeling, drug screening, personalized medicine, and regenerative application. This article systematically summarizes the core strategies of organoids in tissue regeneration, including in vitro modeling and drug screening, in situ transplantation and functional repair, biohybrid organ construction, and organoid chip platform. It further analyzes the major challenges such as insufficient technological maturity, limited functional fidelity, restricted large-scale production, and ethical regulations for clinical application. In addition, potential solutions are proposed to overcome current bottlenecks and challenges through technological integration, standardization and automation, and the promotion of clinical translation. Overall, organoids, as a key strategy in regenerative medicine, are reshaping the landscape of tissue regeneration research and offering new hope for future clinical therapies.

     

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  • [1]
    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.
    [2]
    VerstegenMMA,CoppesRP,BeghinA,et al.Clinical applications of human organoids[J].Nat Med,2025,31(2):409-421.DOI: 10.1038/s41591-024-03489-3.
    [3]
    KenisonJE,StevensNA,QuintanaFJ.Therapeutic induction of antigen-specific immune tolerance[J].Nat Rev Immunol,2024,24(5):338-357.DOI: 10.1038/s41577-023-00970-x.
    [4]
    SilvaAMD,FerreiraJúnior MA,CardosoAIQ,et al.Costs related to obtaining organs for transplantation: a systematic review[J].Transplant Rev (Orlando),2022,36(4):100724.DOI: 10.1016/j.trre.2022.100724.
    [5]
    BirteleM,LancasterM,QuadratoG.Modelling human brain development and disease with organoids[J].Nat Rev Mol Cell Biol,2025,26(5):389-412.DOI: 10.1038/s41580-024-00804-1.
    [6]
    王健,白龙,陈晓,等.骨类器官的构建、评价与应用专家共识(2024版)[J].中华创伤杂志,2024,40(11):974-986.DOI: 10.3760/cma.j.cn501098-20240826-00525.
    [7]
    SatoT,VriesRG,SnippertHJ,et al.Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche[J].Nature,2009,459(7244):262-265.DOI: 10.1038/nature07935.
    [8]
    ZhaoY, LandauS, OkhovatianS, et al. Integrating organoids and organ-on-a-chip devices[J]. Nat Rev Bioeng, 2024, 2(7):588-608. DOI: 10.1038/s44222-024-00207-z.
    [9]
    TangXY,WuS,WangD,et al.Human organoids in basic research and clinical applications[J].Signal Transduct Target Ther,2022,7(1):168.DOI: 10.1038/s41392-022-01024-9.
    [10]
    张涛,崔进,苏佳灿.皮肤类器官构建策略的研究进展[J].中华创伤杂志,2024,40(1):57-64.DOI: 10.3760/cma.j.cn501098-20230728-00030.
    [11]
    YiSA,ZhangY,RathnamC,et al.Bioengineering approaches for the advanced organoid research[J].Adv Mater,2021,33(45):e2007949.DOI: 10.1002/adma.202007949.
    [12]
    YinX,MeadBE,SafaeeH,et al.Engineering stem cell organoids[J].Cell Stem Cell,2016,18(1):25-38.DOI: 10.1016/j.stem.2015.12.005.
    [13]
    VandanaJJ,ManriqueC,LackoLA,et al.Human pluripotent-stem-cell-derived organoids for drug discovery and evaluation[J].Cell Stem Cell,2023,30(5):571-591.DOI: 10.1016/j.stem.2023.04.011.
    [14]
    OkanoH,MorimotoS.iPSC-based disease modeling and drug discovery in cardinal neurodegenerative disorders[J].Cell Stem Cell,2022,29(2):189-208.DOI: 10.1016/j.stem.2022.01.007.
    [15]
    MencheC,FarinHF.Strategies for genetic manipulation of adult stem cell-derived organoids[J].Exp Mol Med,2021,53(10):1483-1494.DOI: 10.1038/s12276-021-00609-8.
    [16]
    张涛,崔进,刘媛媛,等.3D打印皮肤成体干细胞来源类器官人工皮肤修复小鼠皮肤缺损[J].中华创伤杂志,2024,40(1):40-47.DOI: 10.3760/cma.j.cn501098-20230731-00049.
    [17]
    KratochvilMJ,SeymourAJ,LiTL,et al.Engineered materials for organoid systems[J].Nat Rev Mater,2019,4(9):606-622.DOI: 10.1038/s41578-019-0129-9.
    [18]
    KozlowskiMT,CrookCJ,KuHT.Towards organoid culture without Matrigel[J].Commun Biol,2021,4(1):1387.DOI: 10.1038/s42003-021-02910-8.
    [19]
    KimJ,KooBK,KnoblichJA.Human organoids: model systems for human biology and medicine[J].Nat Rev Mol Cell Biol,2020,21(10):571-584.DOI: 10.1038/s41580-020-0259-3.
    [20]
    XuH,LyuX,YiM,et al.Organoid technology and applications in cancer research[J].J Hematol Oncol,2018,11(1):116.DOI: 10.1186/s13045-018-0662-9.
    [21]
    YangL,WangX,ZhouX,et al.A tunable human intestinal organoid system achieves controlled balance between self-renewal and differentiation[J].Nat Commun,2025,16(1):315.DOI: 10.1038/s41467-024-55567-2.
    [22]
    NwokoyePN,AbilezOJ.Bioengineering methods for vascularizing organoids[J].Cell Rep Methods,2024,4(6):100779.DOI: 10.1016/j.crmeth.2024.100779.
    [23]
    GaoQ,WangJ,ZhangH,et al.Organoid vascularization: strategies and applications[J].Adv Healthc Mater,2025,14(20):e2500301.DOI: 10.1002/adhm.202500301.
    [24]
    PolakR,ZhangET,KuoCJ.Cancer organoids 2.0: modelling the complexity of the tumour immune microenvironment[J].Nat Rev Cancer,2024,24(8):523-539.DOI: 10.1038/s41568-024-00706-6.
    [25]
    LiuY,LankadasariM,RosieneJ,et al.Modeling lung adenocarcinoma metastases using patient-derived organoids[J].Cell Rep Med,2024,5(10):101777.DOI: 10.1016/j.xcrm.2024.101777.
    [26]
    TongL,CuiW,ZhangB,et al.Patient-derived organoids in precision cancer medicine[J].Med,2024,5(11):1351-1377.DOI: 10.1016/j.medj.2024.08.010.
    [27]
    陈晓,苏佳灿.骨类器官构建:挑战与应对策略[J].中华创伤杂志,2024,40(1):14-19.DOI: 10.3760/cma.j.cn501098-20230727-00024.
    [28]
    YuanX,WuJ,SunZ,et al.Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure[J].Cell Stem Cell,2024,31(4):484-498.e5.DOI: 10.1016/j.stem.2024.02.005.
    [29]
    WatanabeS,KobayashiS,OgasawaraN,et al.Transplantation of intestinal organoids into a mouse model of colitis[J].Nat Protoc,2022,17(3):649-671.DOI: 10.1038/s41596-021-00658-3.
    [30]
    WangS,DuY,ZhangB,et al.Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient[J].Cell,2024,187(22):6152-6164.e18.DOI: 10.1016/j.cell.2024.09.004.
    [31]
    GuptaN,MatsumotoT,HiratsukaK,et al.Modeling injury and repair in kidney organoids reveals that homologous recombination governs tubular intrinsic repair[J].Sci Transl Med,2022,14(634):eabj4772.DOI: 10.1126/scitranslmed.abj4772.
    [32]
    WangZ,ZhaoF,LangH,et al.Organoids in skin wound healing[J/OL].Burns Trauma,2025,13:tkae077[2026-01-19].https://pubmed.ncbi.nlm.nih.gov/39759541/. DOI: 10.1093/burnst/tkae077.
    [33]
    ZhangT,ShengS,CaiW,et al.3-D bioprinted human-derived skin organoids accelerate full-thickness skin defects repair[J].Bioact Mater,2024,42:257-269.DOI: 10.1016/j.bioactmat.2024.08.036.
    [34]
    RoperJ,TammelaT,CetinbasNM,et al.In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis[J].Nat Biotechnol,2017,35(6):569-576.DOI: 10.1038/nbt.3836.
    [35]
    MusahS,ArzaghiH.Unleashing the power of biomaterials to enhance organoid differentiation and function[J].Nat Methods,2024,21(9):1575-1577.DOI: 10.1038/s41592-024-02393-5.
    [36]
    JebranAF,SeidlerT,TiburcyM,et al.Engineered heart muscle allografts for heart repair in primates and humans[J].Nature,2025,639(8054):503-511.DOI: 10.1038/s41586-024-08463-0.
    [37]
    王健, 白龙, 陈晓, 等. 血管化骨类器官修复早期股骨头缺血性坏死策略[J]. 中华骨与关节外科杂志, 2025, 18(3):193-199. DOI: 10.3969/j.issn.2095-9958.2025.03.01.
    [38]
    SalehT, CaciolliL, GiobbeGG, et al. Ex vivo organ engineering using decellularized tissue scaffolds[J]. Nat Rev Bioeng, 2025, 3(9):761-774. DOI: 10.1038/s44222-025-00322-5.
    [39]
    HuangMS, ChristakopoulosF, RothJG, et al. Organoid bioprinting: from cells to functional tissues[J]. Nat Rev Bioeng, 2025, 3(2):126-142. DOI: 10.1038/s44222-024-00268-0.
    [40]
    ZhouL,HuangJ,LiC,et al.Organoids and organs-on-chips: recent advances, applications in drug development, and regulatory challenges[J].Med,2025,6(4):100667.DOI: 10.1016/j.medj.2025.100667.
    [41]
    FangG, ChenYC, LuH, et al. Advances in spheroids and organoids on a chip[J]. Adv Funct Mater, 2023, 33(19):2215043. DOI: 10.1002/adfm.202215043.
    [42]
    HiratsukaK,MiyoshiT,KrollKT,et al.Organoid-on-a-chip model of human ARPKD reveals mechanosensing pathomechanisms for drug discovery[J].Sci Adv,2022,8(38):eabq0866.DOI: 10.1126/sciadv.abq0866.
    [43]
    LeungCM, de HaanP, Ronaldson-BouchardK, et al. A guide to the organ-on-a-chip[J]. Nat Rev Methods Primers, 2022, 2(1):34. DOI: 10.1038/s43586-022-00118-6.
    [44]
    HarrisonSP,SillerR,TanakaY,et al.Scalable production of tissue-like vascularized liver organoids from human PSCs[J].Exp Mol Med,2023,55(9):2005-2024.DOI: 10.1038/s12276-023-01074-1.
    [45]
    EichmüllerOL,KnoblichJA.Human cerebral organoids - a new tool for clinical neurology research[J].Nat Rev Neurol,2022,18(11):661-680.DOI: 10.1038/s41582-022-00723-9.
    [46]
    KimS, MinS, ChoiYS, et al. Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids[J]. Nat Commun, 2022, 13:1692. DOI: 10.1038/s41467-022-29279-4.
    [47]
    QuintardC, TubbsE, JonssonG, et al. A microfluidic platform integrating functional vascularized organoids-on-chip[J]. Nat Commun, 2024, 15:1452. DOI: 10.1038/s41467-024-45710-4.
    [48]
    ZhengH, FengY, TangJ, et al. Astrocyte-secreted cues promote neural maturation and augment activity in human forebrain organoids[J]. Nat Commun, 2025, 16:2845. DOI: 10.1038/s41467-025-58295-3.
    [49]
    WangD,VillenaveR,Stokar-RegenscheitN,et al.Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges[J].Nat Rev Drug Discov,2026,25(3):204-226.DOI: 10.1038/s41573-025-01317-y.
    [50]
    TanimizuN,IchinoheN,SasakiY,et al.Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo[J].Nat Commun,2021,12(1):3390.DOI: 10.1038/s41467-021-23575-1.
    [51]
    van den BergCW,DumasSJ,LittleMH,et al.Challenges in maturation and integration of kidney organoids for stem cell-based renal replacement therapy[J].Kidney Int,2025,107(2):262-270.DOI: 10.1016/j.kint.2024.10.028.
    [52]
    KellyK,BloorA,GriffinJE,et al.Two-year safety outcomes of iPS cell-derived mesenchymal stromal cells in acute steroid-resistant graft-versus-host disease[J].Nat Med,2024,30(6):1556-1558.DOI: 10.1038/s41591-024-02990-z.
    [53]
    CaulfieldT,ScottC,HyunI,et al.Stem cell research policy and iPS cells[J].Nat Methods,2010,7(1):28-33.DOI: 10.1038/nmeth.f.282.
    [54]
    ShlobinNA, SavulescuJ, BaumML. The ethical landscape of human brain organoids and a mindful innovation framework[J]. Nat Rev Bioeng, 2024, 2(9):785-796. DOI: 10.1038/s44222-024-00211-3.
    [55]
    GeurtsMH, CleversH. CRISPR engineering in organoids for gene repair and disease modelling[J]. Nat Rev Bioeng, 2023, 1(1):32-45. DOI: 10.1038/s44222-022-00013-5.
    [56]
    BaysoyA,BaiZ,SatijaR,et al.The technological landscape and applications of single-cell multi-omics[J].Nat Rev Mol Cell Biol,2023,24(10):695-713.DOI: 10.1038/s41580-023-00615-w.
    [57]
    BlacheU, FordEM, HaB, et al. Engineered hydrogels for mechanobiology[J]. Nat Rev Methods Primers, 2022, 2:98. DOI: 10.1038/s43586-022-00179-7.
    [58]
    OngHT,KaratasE,PoquillonT,et al.Digitalized organoids: integrated pipeline for high-speed 3D analysis of organoid structures using multilevel segmentation and cellular topology[J].Nat Methods,2025,22(6):1343-1354.DOI: 10.1038/s41592-025-02685-4.
    [59]
    BaiL,SuJ.Artificial intelligence virtual organoids (AIVOs)[J].Bioact Mater,2026,59:45-68.DOI: 10.1016/j.bioactmat.2025.12.030.
    [60]
    HoferM,LutolfMP.Engineering organoids[J].Nat Rev Mater,2021,6(5):402-420.DOI: 10.1038/s41578-021-00279-y.
    [61]
    SugimotoS,KobayashiE,FujiiM,et al.An organoid-based organ-repurposing approach to treat short bowel syndrome[J].Nature,2021,592(7852):99-104.DOI: 10.1038/s41586-021-03247-2.
    [62]
    SomaT,OieY,TakayanagiH,et al.Induced pluripotent stem-cell-derived corneal epithelium for transplant surgery: a single-arm, open-label, first-in-human interventional study in Japan[J].Lancet,2024,404(10466):1929-1939.DOI: 10.1016/S0140-6736(24)01764-1.
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