Vascularized bone organoids: current advances and a biomimetic platform for osteonecrosis of the femoral head

Abstract

Osteonecrosis of the femoral head (ONFH) is a devastating ischemic bone disease. Its pathogenesis is multifactorial, including impaired bone remodeling, chronic inflammation, dysregulated lipid metabolism, and bone marrow edema, all intrinsically linked to vascular dysfunction. However, conventional experimental models fail to fully capture the complex pathophysiology of ONFH. Animal models suffer from interspecies differences and are inherently limited in investigating bone marrow edema and femoral head collapse. Therefore, the complex pathogenesis of ONFH remains poorly understood due to the limitations of existing models. Recently, organoids have emerged as a powerful tool for complex and biomimetic disease modeling, with vascularization strategies developed to enhance their structural and functional maturity. The central role of vascular dysfunction in ONFH underscores the value of vascularized bone organoids (VBOs) as a biomimetic model. In this review, we summarize vascularization strategies for bone organoids, including in vitro approaches, in vivo integration, and bioengineering technologies. For ONFH, VBOs provide an advanced experimental model for elucidating disrupted angiogenesis–osteogenesis coupling, inter-tissue crosstalk, and alterations in intraosseous pressure. VBOs also hold significant value for evaluating pro-angiogenic therapies, advancing regenerative medicine, and guiding personalized treatment. Overall, VBOs offer a promising platform for advancing mechanistic insights and therapeutic development in ONFH.

References

[1] Ko Y S, et al. . Updating osteonecrosis of the femoral head. Hip Pelvis, 2023, 35: 147-156

[2] Zhao D, et al. . Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version). J. Orthop. Transl., 2020, 21: 101-110

[3] Liu W, Yue J, Guo X, Wang R, Fu H. Epidemiological investigation and diagnostic analysis of osteonecrosis of the femoral head in three northeastern provinces of China. J. Orthop. Surg. Res., 2024, 19: 292-299

[4] Hines JT, et al. . Osteonecrosis of the femoral head: an updated review of ARCO on pathogenesis, staging and treatment. J. Korean Med. Sci., 2021, 36 e177

[5] Konarski W, et al. . Avascular necrosis of femoral head—overview and current state of the art. Int. J. Environ. Res. Public Health, 2022, 19: 7348

[6] Li Z, et al. . Advances in experimental models of osteonecrosis of the femoral head. J. Orthop. Transl., 2023, 3988-99

[7] Liu H, Triffitt JT, Xia Z, Su J. Artificial intelligence-enabled studies on organoid and organoid extracellular vesicles. Biomater. Transl., 2024, 5: 236-256

[8] Gao, Q. et al. Organoid vascularization: strategies and applications. Adv. Healthc. Mater. 14, e2500301 (2025).

[9] Shin YJ, Safina D, Zheng Y, Levenberg S. Microvascularization in 3D human engineered tissue and organoids. Annu. Rev. Biomed. Eng., 2025, 27: 473-498

[10] Li S, et al. . Cell communication and relevant signaling pathways in osteogenesis-angiogenesis coupling. Bone Res., 2025, 13: 45

[11] Wang J, et al. . Standardization and consensus in the development and application of bone organoids. Theranostics, 2025, 15682-706

[12] Shao W, et al. . Unraveling the role of endothelial dysfunction in osteonecrosis of the femoral head: a pathway to new therapies. Biomedicines, 2024, 12: 664

[13] Li L, et al. . Pathological mechanisms and related markers of steroid-induced osteonecrosis of the femoral head. Ann. Med., 2024, 562416070

[14] Lee E-J, et al. . Glucocorticoids alter bone microvascular barrier via MAPK/Connexin43 mechanisms. Adv. Healthc. Mater., 2025, 14 e2404302

[15] Fan X, et al. . Establishment of the multi-component bone-on-a-chip: to explore therapeutic potential of DNA aptamers on endothelial cells. Front. Cell Dev. Biol., 2023, 111183163

[16] Li T, Liu Y, Zhang Q, Sun W, Dong Y. A steroid-induced osteonecrosis model established using an organ-on-a-chip platform. Exp. Ther. Med., 2021, 221070

[17] Tuckermann J, Adams RH. The endothelium-bone axis in development, homeostasis and bone and joint disease. Nat. Rev. Rheumatol., 2021, 17608-620

[18] Filipowska J, Tomaszewski KA, Niedźwiedzki Ł, Walocha JA, Niedźwiedzki T. The role of vasculature in bone development, regeneration and proper systemic functioning. Angiogenesis, 2017, 20: 291-302

[19] Yellowley CE, Genetos DC. Hypoxia signaling in the skeleton: implications for bone health. Curr. Osteoporos. Rep., 2019, 17: 26-35

[20] Owen-Woods C, Kusumbe A. Fundamentals of bone vasculature: specialization, interactions and functions. Semin. Cell Dev. Biol., 2022, 123: 36-47

[21] Langen UH, et al. . Cell-matrix signals specify bone endothelial cells during developmental osteogenesis. Nat. Cell Biol., 2017, 19: 189-201

[22] Zhang J, Pan J, Jing W. Motivating role of type H vessels in bone regeneration. Cell Prolif., 2020, 53 e12874

[23] Spencer JA, et al. . Direct measurement of local oxygen concentration in the bone marrow of live animals. Nature, 2014, 508: 269-273

[24] Acar M, et al. . Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal. Nature, 2015, 526: 126-130

[25] Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature, 2014, 507: 323-328

[26] Dzamukova M, et al. . Mechanical forces couple bone matrix mineralization with inhibition of angiogenesis to limit adolescent bone growth. Nat. Commun., 2022, 13 3059

[27] Hendriks M, Ramasamy SK. Blood vessels and vascular niches in bone development and physiological remodeling. Front. Cell Dev. Biol., 2020, 8: 602278

[28] Mohanakrishnan V, et al. . Specialized post-arterial capillaries facilitate adult bone remodelling. Nat. Cell Biol., 2024, 262020-2034

[29] Tamma R, Ribatti D. Bone niches, hematopoietic stem cells, and vessel formation. Int. J. Mol. Sci., 2017, 18: 151

[30] Stegen S, Carmeliet G. Mechanisms of bone development and repair. Nat. Rev. Endocrinol., 2024, 20399-413

[31] Sivaraj KK, Adams RH. Blood vessel formation and function in bone. Development, 2016, 143: 2706-2715

[32] Valderrábano RJ, Wu JY. Bone and blood interactions in human health and disease. Bone, 2019, 119: 65-70

[33] Grellier M, Bordenave L, Amédée J. Cell-to-cell communication between osteogenic and endothelial lineages: implications for tissue engineering. Trends Biotechnol., 2009, 27: 562-571

[34] Perepletchikova D, Malashicheva A. Communication between endothelial cells and osteoblasts in regulation of bone homeostasis: notch players. Stem Cell Res. Ther., 2025, 16: 56

[35] Bouland C, et al. . Cross-talk between mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) in bone regeneration. Front. Cell Dev. Biol., 2021, 9674084

[36] Wirsig K, Bürger N, Bernhardt A. Crosstalk between endothelial cells and osteoblasts stimulates ALP via Notch signaling and RANKL/OPG ratio independently of Notch signaling in vitro. Cell. Mol. Biol. Lett., 2025, 30108

[37] Perepletchikova D, et al. . Endothelial-mesenchymal crosstalk drives osteogenic differentiation of human osteoblasts through notch signaling. Cell Commun. Signal., 2025, 23100

[38] Huang S, et al. . Advancements in bone organoids: perspectives on construction methodologies and application strategies. J. Adv. Res., 2026, 81745-767

[39] Bi M, Yang K, Yu T, Wu G, Li Q. Cell-based mechanisms and strategies of co-culture system both in vivo and vitro for bone tissue engineering. Biomed. Pharmacother., 2023, 169: 115907

[40] Kuss MA, et al. . Prevascularization of 3D printed bone scaffolds by bioactive hydrogels and cell co-culture. J. Biomed. Mater. Res. B Appl. Biomater., 2018, 1061788-1798

[41] Pirosa A, et al. . An in vitro chondro-osteo-vascular triphasic model of the osteochondral complex. Biomaterials, 2021, 272 120773

[42] Duan J, et al. . 3D bioprinting of prevascularized bone organoids for rapid in situ cranial bone reconstruction. Adv. Healthc. Mater., 2025, 14 e2501376

[43] Heo DN, Hospodiuk M, Ozbolat IT. Synergistic interplay between human MSCs and HUVECs in 3D spheroids laden in collagen/fibrin hydrogels for bone tissue engineering. Acta Biomater., 2019, 95: 348-356

[44] Lou X, et al. . Sequential angiogenic-osteogenic coupling via a spatiotemporally graded hydrogel enables vascularized bone organoids for critical-sized calvarial defect reconstruction. Compos Part B Eng., 2025, 302 112553

[45] Gai T, et al. . Sequential construction of vascularized and mineralized bone organoids using engineered ECM-DNA-CPO-based bionic matrix for efficient bone regeneration. Bioact. Mater., 2025, 49: 362-377

[46] Janebodin K, Zeng Y, Buranaphatthana W, Ieronimakis N, Reyes M. VEGFR2-dependent angiogenic capacity of pericyte-like dental pulp stem cells. J. Dent. Res., 2013, 92: 524-531

[47] Li A, et al. . Vascularization of a bone organoid using dental pulp stem cells. Stem Cells Int., 2023, 2023: 5367887

[48] Gao, Q. et al. Personalized bone organoid using iPSC-derived cells for clinically relevant applications. Preprint at https://doi.org/10.21203/rs.3.rs-5349885/v1 (2024).

[49] Shen Y, et al. . comBO: a combined human bone and lympho-myeloid bone marrow organoid for preclinical modeling of hematopoietic disorders. Cell Stem Cell, 2026, 33421-437.e7

[50] Li Q, et al. . Macro-scale, scaffold-assisted model of the human bone marrow endosteal niche using hiPSC-vascularized osteoblastic organoids. Cell Stem Cell, 2025, 32: 1941-1958.e8

[51] Abraham DM, et al. . Self-assembling human skeletal organoids for disease modeling and drug testing. J. Biomed. Mater. Res. B Appl. Biomater., 2022, 110: 871-884

[52] Wu J, et al. . Stromal vascular fraction self-assembles vascularized osteogenic organoids with immunomodulatory functions. Bioact. Mater., 2026, 57: 323-343

[53] Qian, T. et al. Self-organizing vascularized subchondral bone organoids from stromal vascular fraction enable functional osteochondral interface regeneration. Organoid Res.https://doi.org/10.36922/OR025480037.

[54] Shah Mohammadi M, et al. . Critical considerations for regeneration of vascularized composite tissues. Tissue Eng. B Rev., 2021, 27: 366-381

[55] Lin C-H, et al. . The use of hydrogel microspheres as cell and drug delivery carriers for bone, cartilage, and soft tissue regeneration. Biomater. Transl., 2024, 5: 93-94

[56] Li, R. et al. Mechano-responsive biomaterials for bone organoid construction. Adv. Healthc. Mater. 14, e2404345 (2024).

[57] Riddle RC, Khatri R, Schipani E, Clemens TL. Role of hypoxia-inducible factor-1alpha in angiogenic-osteogenic coupling. J. Mol. Med., 2009, 87: 583-590

[58] Zhu M, et al. . Dynamic GelMA/DNA dual-network hydrogels promote woven bone organoid formation and enhance bone regeneration. Adv. Mater., 2025, 37 e2501254

[59] Deng A, et al. . Microsphere strategy to generate conformal bone organoid units with osteoimmunomodulation and sustainable oxygen supply for bone regeneration. Adv. Sci., 2025, 12 e01437

[60] Zhang Y, et al. . Immune-instructive bone organoids via non-immunogenic plant-based bioinks for enhanced bone repair. Matter, 2026, 9 102651

[61] Moccia F, Negri S, Shekha M, Faris P, Guerra G. Endothelial Ca2+ signaling, angiogenesis and vasculogenesis: just what it takes to make a blood vessel. Int. J. Mol. Sci., 2019, 20: 3962

[62] Yang Z, et al. . In situ self-assembled organoid for osteochondral tissue regeneration with dual functional units. Bioact. Mater., 2023, 27200-215

[63] Wang J, et al. . Protocol for engineering bone organoids from mesenchymal stem cells. Bioact. Mater., 2025, 45: 388-400

[64] Wang J, et al. . Engineering large-scale self-mineralizing bone organoids with bone matrix-inspired hydroxyapatite hybrid bioinks. Adv. Mater., 2024, 36 e2309875

[65] Zhang X, et al. . Divide-and-conquer strategy with engineered ossification center organoids for rapid bone healing through developmental cell recruitment. Nat. Commun., 2025, 16 6200

[66] Liu H, et al. . Recent advancement in vascularized tissue-engineered bone based on materials design and modification. Mater. Today Bio, 2023, 23 100858

[67] Yang Q, et al. . A new paradigm in bone tissue biomaterials: enhanced osteogenesis-angiogenic coupling by targeting H-type blood vessels. Biomaterials, 2026, 324 123423

[68] Polak M, Karbowniczek JE, Stachewicz U. Strategies in electrospun polymer and hybrid scaffolds for enhanced cell integration and vascularization for bone tissue engineering and organoids. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnology, 2024, 16 e2022

[69] Huang D, et al. . Biomimetic structural design in 3D-printed scaffolds for bone tissue engineering. Mater. Today Bio, 2025, 32 101664

[70] Kronenberg HM. Developmental regulation of the growth plate. Nature, 2003, 423: 332-336

[71] Bahney CS, Hu DP, Miclau T, Marcucio RS. The multifaceted role of the vasculature in endochondral fracture repair. Front. Endocrinol., 2015, 6: 4

[72] Bukhari MMM, Khabooshani M, Naqvi SM, McNamara LM. Estrogen deficiency alters vascularization and mineralization dynamics: insight from a novel 3-D humanized and vascularized bone organoid model. Am. J. Physiol. Cell Physiol., 2025, 328C743-C756

[73] Freeman FE, Haugh MG, McNamara LM. An in vitro bone tissue regeneration strategy combining chondrogenic and vascular priming enhances the mineralization potential of mesenchymal stem cells in vitro while also allowing for vessel formation. Tissue Eng. A, 2015, 21: 1320-1332

[74] Su Y, et al. . Synergistic promotion of bone regeneration through co-culture of endothelial cells with mesenchymal stem cells in endochondral ossification organoids. Stem Cell Res. Ther., 2025, 16: 647

[75] Lin Z, et al. . Engineering pre-vascularized bone-like tissue from human mesenchymal stem cells through simulating endochondral ossification. Biomaterials, 2022, 283 121451

[76] Kesharwani A, et al. . Modeling vascular dynamics at the initial stage of endochondral ossification on a microfluidic chip using a human embryonic-stem-cell-derived organoid. Regen. Ther., 2025, 2890-100

[77] Whelan, I. T. et al. A microphysiological model of bone development and regeneration. Biofabrication15, 034103 (2023).

[78] Takasato, M., Er, P. X., Chiu, H. S. & Little, M. H. Generation of kidney organoids from human pluripotent stem cells. Nat. Protoc. 11, 1681–1692 (2016).

[79] Jiao Y, Lu S, Zhang J, Zhen J. Applications in osteochondral organoids for osteoarthritis research: from pathomimetic modeling to tissue engineering repair. Front. Bioeng. Biotechnol., 2025, 13: 1629608

[80] Hall GN, et al. . Patterned, organoid-based cartilaginous implants exhibit zone specific functionality forming osteochondral-like tissues in vivo. Biomaterials, 2021, 273 120820

[81] Lamandé, S. R. et al. Modeling human skeletal development using human pluripotent stem cells. Proc. Natl. Acad. Sci. USA120, e2211510120 (2023).

[82] Faeed M, Ghiasvand M, Fareghzadeh B, Taghiyar L. Osteochondral organoids: current advances, applications, and upcoming challenges. Stem Cell Res. Ther., 2024, 15183

[83] Xiong J, et al. . Recapitulation of endochondral ossification by hPSC-derived SOX9+ sclerotomal progenitors. Nat. Commun., 2025, 16 2781

[84] Boutom SM, et al. . Central nervous system vascularization in human embryos and neural organoids. Cell Rep., 2024, 43115068

[85] Najdanović, J. G. et al. Vascularization and osteogenesis in ectopically implanted bone tissue-engineered constructs with endothelial and osteogenic differentiated adipose-derived stem cells. World J. Stem Cells13, 91–114 (2021).

[86] Hong Y, et al. . Bone organoid construction and evolution. J. Orthop. Transl., 2025, 53260

[87] Hao S, et al. . Microenvironment-targeted strategy steers advanced bone regeneration. Mater. Today Bio, 2023, 22 100741

[88] Fu J, Wang D-A. In situ organ-specific vascularization in tissue engineering. Trends Biotechnol., 2018, 36834-849

[89] Chen Z, et al. . Single BMSC-derived cartilage organoids for gradient heterogeneous osteochondral regeneration by leveraging native vascular microenvironment. J. Nanobiotechnology, 2025, 23: 325

[90] Zhang Y, et al. . 3D-bioprinted anisotropic bicellular living hydrogels boost osteochondral regeneration via reconstruction of cartilage-bone interface. Innovation, 2024, 5100542

[91] Motoike S, Inada Y, Toguchida J, Kajiya M, Ikeya M. Jawbone-like organoids generated from human pluripotent stem cells. Nat. Biomed. Eng., 2025, 91816-1834

[92] Kong Y, et al. . Advance in the application of organoids in bone diseases. Front. Cell Dev. Biol., 2024, 12: 1459891

[93] Meng F, et al. . A trabeculae-like biomimetic bone-filling material as a potential organoid for bone defect treatment. Organoid Res., 2025, 125040003

[94] Zhou R, et al. . Vascularised organoids: recent advances and applications in cancer research. Clin. Transl. Med., 2025, 15 e70258

[95] Nejati O, et al. . Bone-on-a-chip technology review: clinical applications, scientific advancements, and challenges. J. Drug Delivery Sci. Technol., 2025, 114107565

[96] Verdugo-Avello F, Wychowaniec JK, Villacis-Aguirre CA, D’Este M, Toledo JR. Bone microphysiological models for biomedical research. Lab Chip, 2025, 25806-836

[97] Lim J, et al. . The edifice of vasculature-on-chips: a focused review on the key elements and assembly of angiogenesis models. ACS Biomater. Sci. Eng., 2024, 10: 3548-3567

[98] Jusoh N, Oh S, Kim S, Kim J, Jeon NL. Microfluidic vascularized bone tissue model with hydroxyapatite-incorporated extracellular matrix. Lab Chip, 2015, 15: 3984-3988

[99] Sanaei F, et al. . Harnessing advances in bone tissue engineering for design of bone-on-chip systems. Adv. Healthc. Mater., 2026, 15 e03525

[100] Bersini S, et al. . Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach. Biomaterials, 2016, 76: 157-172

[101] Bertassoni LE, et al. . Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip, 2014, 14: 2202-2211

[102] Marturano-Kruik A, et al. . Human bone perivascular niche-on-a-chip for studying metastatic colonization. Proc. Natl. Acad. Sci. USA, 2018, 115: 1256-1261

[103] Ji X, et al. . Premetastatic niche mimicking bone-on-a-chip: a microfluidic platform to study bone metastasis in cancer patients. Small, 2023, 19 2207606

[104] Salehi S, Brambilla S, Rasponi M, Lopa S, Moretti M. Development of a microfluidic vascularized osteochondral model as a drug testing platform for osteoarthritis. Adv. Healthc. Mater., 2024, 13: 2402350

[105] Jeon JS, et al. . Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation. Proc. Natl. Acad. Sci. USA, 2015, 112214-219

[106] Liu Q, et al. . Engineering in vitro vascular microsystems. Microsyst. Nanoeng., 2025, 11: 100

[107] Konopka J, Żuchowska A, Jastrzębska E. Vascularized tumor-on-chip microplatforms for the studies of neovasculature as hope for more effective cancer treatments. Biosens. Bioelectron., 2024, 249115986

[108] Sano E, et al. . Engineering of vascularized 3D cell constructs to model cellular interactions through a vascular network. Biomicrofluidics, 2018, 1242204

[109] Crippa M, et al. . A microfluidic model of human vascularized breast cancer metastasis to bone for the study of neutrophil-cancer cell interactions. Mater. Today Bio, 2022, 17 100460

[110] Neto E, et al. . Micropathological chip modeling the neurovascular unit response to inflammatory bone condition. Adv. Healthc. Mater., 2022, 11 e2102305

[111] Smith KWY, et al. . Developing an in vitro osteochondral micro-physiological system for modeling cartilage-bone crosstalk in arthritis. Front. Immunol., 2025, 161495613

[112] Cheng X, et al. . Advances in bone-on-a-chips for in vitro modeling of bone physiology and pathology. Biomedicines, 2026, 14710

[113] Zhang YS, et al. . 3D bioprinting for tissue and organ fabrication. Ann. Biomed. Eng., 2017, 45148-163

[114] Kérourédan O, et al. . Micropatterning of endothelial cells to create a capillary-like network with defined architecture by laser-assisted bioprinting. J. Mater. Sci. Mater. Med., 2019, 30: 28

[115] Anada T, et al. . Vascularized bone-mimetic hydrogel constructs by 3D bioprinting to promote osteogenesis and angiogenesis. Int. J. Mol. Sci., 2019, 201096

[116] Khanmohammadi M, Volpi M, Walejewska E, Olszewska A, Swieszkowski W. Printing of 3D biomimetic structures for the study of bone metastasis: a review. Acta Biomater., 2024, 17824-40

[117] Sexton ZA, et al. . Rapid model-guided design of organ-scale synthetic vasculature for biomanufacturing. Science, 2025, 388: 1198-1204

[118] Zhao X, et al. . Beyond hype: unveiling the Real challenges in clinical translation of 3D printed bone scaffolds and the fresh prospects of bioprinted organoids. J. Nanobiotechnology, 2024, 22: 500

[119] Chen Y, et al. . Evolutionary course of the femoral head osteonecrosis: histopathological-radiologic characteristics and clinical staging systems. J. Orthop. Transl., 2022, 3228-40

[120] Peng Y, et al. . Glucocorticoids disrupt skeletal angiogenesis through transrepression of NF-κB-mediated preosteoclast PDGFB transcription in young mice. J. Bone Miner. Res., 2020, 35: 1188-1202

[121] Zhang F, et al. . FAR591 promotes the pathogenesis and progression of SONFH by regulating fos expression to mediate the apoptosis of bone microvascular endothelial cells. Bone Res., 2023, 11: 27

[122] Wang P, et al. . Angiogenesis of avascular necrosis of the femoral head: a classic treatment strategy. Biomedicines, 2024, 122577

[123] Ma T, et al. . Research progress in the pathogenesis of hormone-induced femoral head necrosis based on microvessels: a systematic review. J. Orthop. Surg. Res., 2024, 19265

[124] Wu, Y. et al. Osteocytes: master orchestrators of skeletal homeostasis, remodeling, and osteoporosis pathogenesis. Front. Cell Dev. Biol. 13, 1670716 (2025).

[125] Zhang Q, Sun W, Li T, Liu F. Polarization behavior of bone macrophage as well as associated osteoimmunity in glucocorticoid-induced osteonecrosis of the femoral head. J. Inflammation Res., 2023, 16879-894

[126] Ma M, et al. . Infographic: osteoimmunology mechanism of osteonecrosis of the femoral head. Bone Jt. Res., 2022, 11: 29-31

[127] Zhang, Q., L. V, J. & Jin, L. Role of coagulopathy in glucocorticoid-induced osteonecrosis of the femoral head. J. Int. Med. Res. 46, 2141–2148 (2018).

[128] Koenen M, Hill MA, Cohen P, Sowers JR. Obesity, adipose tissue and vascular dysfunction. Circ. Res., 2021, 128: 951-968

[129] Mo L, et al. . The pathomechanism of bone marrow edema in the femoral head necrosis with pericollapse stage. Sci. Rep., 2025, 15 1166

[130] Li Z, et al. . The role of Piezo1 in bone marrow stem cells in response to elevated intraosseous pressure on regulating osteogenesis and angiogenesis of steroid-induced osteonecrosis of the femoral head. J. Orthop. Transl., 2025, 51: 278-289

[131] Zhou R, et al. . Advances in the mechanism for steroid-induced osteonecrosis of the femoral head. Bone Res., 2026, 14: 23

[132] Liu H, et al. . Lymphatic-immune interactions in the musculoskeletal system. Front. Immunol., 2025, 161578847

[133] Biswas L, et al. . Lymphatic vessels in bone support regeneration after injury. Cell, 2023, 186382-397.e24

[134] Gao Y, Zhu H, Wang Q, Feng Y, Zhang C. Inhibition of PERK signaling prevents against glucocorticoid-induced endotheliocyte apoptosis and osteonecrosis of the femoral head. Int. J. Biol. Sci., 2020, 16: 543-552

[135] Kerachian MA, Harvey EJ, Cournoyer D, Chow TYK, Séguin C. Avascular necrosis of the femoral head: vascular hypotheses. Endothelium, 2006, 13: 237-244

[136] Yao X, et al. . PTEN inhibitor VO-OHpic attenuates GC-associated endothelial progenitor cell dysfunction and osteonecrosis of the femoral head via activating Nrf2 signaling and inhibiting mitochondrial apoptosis pathway. Stem Cell Res. Ther., 2020, 11: 140

[137] Singh M, et al. . A molecular troika of angiogenesis, coagulopathy and endothelial dysfunction in the pathology of avascular necrosis of femoral head: a comprehensive review. Cells, 2023, 122278

[138] Fan M, Peng J, Qin L, Lu S. Experimental animal models of osteonecrosis. Rheumatol. Int., 2011, 31983-994

[139] Ma J, et al. . Animal models of femur head necrosis for tissue engineering and biomaterials research. Tissue Eng. Part C Methods, 2022, 28: 214-227

[140] Bai L, et al. . Engineering bone/cartilage organoids: strategy, progress, and application. Bone Res., 2024, 12: 66

[141] Kim J-I, et al. . Human assembloid model of the ascending neural sensory pathway. Nature, 2025, 642143-153

[142] Chen Y, et al. . Sophisticated interfaces between biosensors and organoids: advancing towards intelligent multimodal monitoring physiological parameters. Biosensors, 2025, 15: 557

[143] Li H, et al. . Identification of type H vessels in mice mandibular condyle. J. Dent. Res., 2021, 100983-992

[144] Peng Y, Wu S, Li Y, Crane JL. Type H blood vessels in bone modeling and remodeling. Theranostics, 2020, 10: 426-436

[145] Zhang X-X, et al. . Bone marrow mesenchymal stem cells overexpressing HIF-1α prevented the progression of glucocorticoid-induced avascular osteonecrosis of femoral heads in mice. Cell Transplant., 2022, 31: 9636897221082687

[146] Shapiro F, et al. . Femoral head deformation and repair following induction of ischemic necrosis: a histologic and magnetic resonance imaging study in the piglet. J. Bone Jt. Surg. Am., 2009, 912903-2914

[147] Liao, A., Xiong, J., Tong, Z., Zhou, L. & Liu, J. Microfluidic chamber design for organ-on-a-chip: a computational fluid dynamics study of pillar geometry and pulsatile perfusion. Biosensors16, 49 (2026).

[148] Zhang J, Cao J, Liu Y, Zhao H. Advances in the pathogenesis of steroid-associated osteonecrosis of the femoral head. Biomolecules, 2024, 14: 667

[149] Birey F, et al. . Assembly of functionally integrated human forebrain spheroids. Nature, 2017, 54554-59

[150] Cheng Y, et al. . Early depletion of M1 macrophages retards the progression of glucocorticoid-associated osteonecrosis of the femoral head. Int. Immunopharmacol., 2023, 122: 110639

[151] Zheng J, Yao Z, Xue L, Wang D, Tan Z. The role of immune cells in modulating chronic inflammation and osteonecrosis. Front. Immunol., 2022, 131064245

[152] Liu G, et al. . M2 macrophages-derived exosomes for osteonecrosis of femoral head treatment: modulating neutrophil extracellular traps formation and endothelial phenotype transition. Bone Res., 2025, 1342

[153] Yu R, et al. . Inhibition of toll-like receptor 4 signaling pathway accelerates the repair of avascular necrosis of femoral epiphysis through regulating macrophage polarization in perthes disease. Tissue Eng. Regener. Med., 2023, 20489-501

[154] Duan P, et al. . Exosomal miR-1a-3p derived from glucocorticoid-stimulated M1 macrophages promotes the adipogenic differentiation of BMSCs in glucocorticoid-associated osteonecrosis of the femoral head by targeting Cebpz. J. Nanobiotechnology, 2024, 22: 648

[155] Duan X, et al. . Bioinformatic analysis of related immune cell infiltration and key genes in the progression of osteonecrosis of the femoral head. Front. Immunol., 2023, 141340446

[156] Chen Y, et al. . Dendritic cells-derived interferon-λ1 ameliorated inflammatory bone destruction through inhibiting osteoclastogenesis. Cell Death Dis., 2020, 11 414

[157] Lou X, et al. . Innovative strategies for bone organoid: synergistic application and exploration of advanced technologies. J. Orthop. Transl., 2025, 54180-198

[158] Mattsson C, Olsson T. Estrogens and glucocorticoid hormones in adipose tissue metabolism. Curr. Med. Chem., 2007, 14: 2918-2924

[159] Zhang S, et al. . Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes. J. Transl. Med., 2025, 23 592

[160] Li H, et al. . The multifaceted roles of extracellular vesicles in osteonecrosis of the femoral head. J. Orthop. Transl., 2025, 52: 70-84

[161] Duan D-Y, Tang J, Tian H-T, Shi Y-Y, Jia J. Adipocyte-secreted microvesicle-derived miR-148a regulates adipogenic and osteogenic differentiation by targeting Wnt5a/Ror2 pathway. Life Sci, 2021, 278: 119548

[162] Zhang M, et al. . Serum exosomal hsa-miR-135b-5p serves as a potential diagnostic biomarker in steroid-induced osteonecrosis of femoral head. Am. J. Transl. Res., 2020, 122136-2154

[163] Wang X-Y, et al. . Altered lipidomic profiles in patients with and without osteonecrosis of the femoral head after 1-month glucocorticoid treatment. Clin. Transl. Med., 2021, 11 e298

[164] Finch ER, et al. . Fenofibrate reduces osteonecrosis without affecting antileukemic efficacy in dexamethasone-treated mice. Haematologica, 2021, 106: 2095-2101

[165] Rodriguez-Cuenca S, Pellegrinelli V, Campbell M, Oresic M, Vidal-Puig A. Sphingolipids and glycerophospholipids—the ‘ying and yang’ of lipotoxicity in metabolic diseases. Prog. Lipid Res., 2017, 66: 14-29

[166] Higashi Y. Endothelial function in dyslipidemia: roles of LDL-cholesterol, HDL-cholesterol and triglycerides. Cells, 2023, 12: 1293

[167] Kopych V, Da Costa ADS, Park K. Endothelial dysfunction in atherosclerosis: experimental models and therapeutics. Biomater. Res., 2025, 29 252

[168] Xiang D, et al. . Exosomal SPRY4 from adipogenic BMSCs impairs angiogenesis via the PTPRB/TIE2/PI3K axis in steroid-induced osteonecrosis of the femoral head. Stem Cell Res. Ther., 2025, 16375

[169] Yang Y, et al. . Exploring microfluidics-based organoid interactions through analysis of albumin secretion. Lab Chip, 2025, 25487-499

[170] Qi L, et al. . Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system. Nat Commun, 2024, 15 7991

[171] Tidball AM, et al. . Lysophosphatidic acid and sphingosine-1-phosphate are apical polarity cues in multiple organoid systems. Cell Rep., 2025, 44: 115842

[172] Zheng Y, et al. . Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs. Nat. Commun., 2025, 16 829

[173] Sato M, et al. . Microcirculation-on-a-chip: a microfluidic platform for assaying blood- and lymphatic-vessel permeability. PLoS ONE, 2015, 10e0137301

[174] H, W. et al. Synergistic effects of mTOR inhibitors with VEGFR3 inhibitors on the interaction between TSC2-mutated cells and lymphatic endothelial cells. Sci. China Life Sci. 68, 1676–1688 (2025).

[175] Zhao, X.-Y. et al. Adipose tissue engineering biomaterials: smart scaffolds, vascularization, and clinical frontiers. Biomolecules16, 362 (2026).

[176] Yang T, Fang Z, Zhang J, Zheng S. Physical cues in biomaterials modulate macrophage polarization for bone regeneration: a review. Front. Bioeng. Biotechnol., 2025, 131640560

[177] Papamichail L, Koch LS, Veerman D, Broersen K, van der Meer AD. Organoids-on-a-chip: microfluidic technology enables culture of organoids with enhanced tissue function and potential for disease modeling. Front. Bioeng. Biotechnol., 2025, 131515340

[178] Kim D, et al. . From organoid culture to manufacturing: technologies for reproducible and scalable organoid production. npj Biomed. Innov., 2026, 312

[179] Tarantino U, et al. . Bone marrow edema: overview of etiology and treatment strategies. J. Bone Jt. Surg., 2022, 104189-200

[180] Akhavan S, Martinkovich SC, Kasik C, DeMeo PJ. Bone marrow edema, clinical significance, and treatment options: a review. J. Am. Acad. Orthop. Surg., 2020, 28: e888-e899

[181] Di Martino A, et al. . Bone marrow edema of the hip: a narrative review. Arch. Orthop. Trauma Surg., 2023, 143: 6901-6917

[182] Kim M, et al. . Multimodal characterization of cardiac organoids using integrations of pressure-sensitive transistor arrays with three-dimensional liquid metal electrodes. Nano Lett., 2022, 22: 7892-7901

[183] Ernits M, Reinsalu O, Kyritsakis A, Linko V, Zadin V. Low-cost, open-source, high-precision pressure controller for multi-channel microfluidics. Biosensors, 2025, 15: 154

[184] Esteban-Linares A, et al. . Dynamic observation of retinal response to pressure elevation in a microfluidic chamber. Anal. Chem., 2022, 9412297-12304

[185] Zhao H, Yeersheng R, Xia Y, Kang P, Wang W. Hypoxia enhanced bone regeneration through the HIF-1α/β-catenin pathway in femoral head osteonecrosis. Am. J. Med. Sci., 2021, 362: 78-91

[186] Liao H, et al. . Bone mesenchymal stem cells co-expressing VEGF and BMP-6 genes to combat avascular necrosis of the femoral head. Exp. Ther. Med., 2018, 15: 954-962

[187] Zhang H-X, et al. . In vitro and in vivo evaluation of calcium phosphate composite scaffolds containing BMP-VEGF loaded PLGA microspheres for the treatment of avascular necrosis of the femoral head. Mater. Sci. Eng. C Mater. Biol. Appl., 2016, 60: 298-307

[188] Xu D-F, Qu G-X, Yan S-G, Cai X-Z. Microbubble-mediated ultrasound outweighs low-intensity pulsed ultrasound on osteogenesis and neovascularization in a rabbit model of steroid-associated osteonecrosis. Biomed. Res. Int., 2018, 2018: 4606791

[189] Cui F, et al. . Detection of AD-BMP-2-IRES-HIF-1α MU on local promoting angiogenic and osteogenic capacity of necrosis area. Pak. J. Pharm. Sci., 2017, 302013-2019

[190] Peyravian N, et al. . Designing and synthesis of injectable hydrogel based on carboxymethyl cellulose/carboxymethyl chitosan containing QK peptide for femoral head osteonecrosis healing. Int. J. Biol. Macromol., 2024, 270: 132127

[191] Soragni C, et al. . Phenotypic screening in organ-on-a-chip systems: a 1537 kinase inhibitor library screen on a 3D angiogenesis assay. Angiogenesis, 2024, 2737-49

[192] Xiang X-N, He H-C, He C-Q. Advances in mechanism and management of bone homeostasis in osteonecrosis: a review article from basic to clinical applications. Int. J. Surg., 2025, 111: 1101-1122

[193] Qi T, Yan Y, Qi W, Chen W, Yang H. Hip joint-preserving strategies for treating osteonecrosis of the femoral head: from nonoperative to operative procedures. J. Orthop. Transl., 2025, 51: 256-277

[194] Xie X, et al. . Relieving oxidative stress microenvironment and promoting vascularized bone formation to treat femoral head necrosis using 3D-printed scaffold with ultralong-term multienzyme-like activity. J. Orthop. Transl., 2025, 53: 206-220

[195] Baek S-H, et al. . Evaluation of safety and efficacy of cell therapy based on osteoblasts derived from umbilical cord mesenchymal stem cells for osteonecrosis of the femoral head: study protocol for a single-center, open-label, Phase I clinical trial. Pharmaceuticals, 2024, 17: 1366

[196] Hauzeur J-P, et al. . Did osteoblastic cell therapy improve the prognosis of pre-fracture osteonecrosis of the femoral head? A randomized, controlled trial. Clin. Orthop., 2020, 4781307-1315

[197] Jayankura M, et al. . Does adjunction of autologous osteoblastic cells improve the results of core decompression in early-stage femoral head osteonecrosis? A double-blind, randomized trial. Clin. Orthop. Relat. Res., 2023, 481: 1527

[198] Kang Y, Kang TH, Ro HS, Hwang NS, Kim HD. Engineering osteogenic spheroids: the impact of endothelial cell localization on vascularization and differentiation. Adv. Healthc. Mater., 2025, 14 e2501390

[199] Gao Y, et al. . Self-organized vascularized microtissue based on the human microvascular unit for tissue repair and regeneration. ACS Appl. Mater. Interfaces, 2025, 1741554-41570

[200] Zhu W, et al. . Bioengineering strategies targeting angiogenesis: innovative solutions for osteonecrosis of the femoral head. J. Tissue Eng., 2025, 16 20417314241310541

[201] Wu T, et al. . Translational horizons in stem cell therapy for osteonecrosis of the femoral head: a journey from basic research to clinical practice through bibliometric insights. J. Transl. Med., 2024, 22 982

[202] Shariati L, Esmaeili Y, Haghjooy Javanmard S, Bidram E, Amini A. Organoid technology: current standing and future perspectives. Stem Cells, 2021, 39: 1625-1649

[203] Huang C, Qing L, Xiao Y, Tang J, Wu P. Insight into steroid-induced ONFH: the molecular mechanism and function of epigenetic modification in mesenchymal stem cells. Biomolecules, 2023, 14: 4

[204] Liao Z, et al. . Single-cell transcriptome analysis reveals aberrant stromal cells and heterogeneous endothelial cells in alcohol-induced osteonecrosis of the femoral head. Commun. Biol., 2022, 5324

[205] Fang L, et al. . SIRT6 prevents glucocorticoid-induced osteonecrosis of the femoral head in rats. Oxid. Med. Cell. Longevity, 2022, 2022 6360133

[206] Cerneckis J, Cai H, Shi Y. Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications. Signal Transduct. Target. Ther., 2024, 9112

[207] Moseki MC, Makhzoum A, Masisi K, Gaobotse G. Recent progress in the use of induced pluripotent stem cells in novel drug development over the past 5 years (2020–2024). Discov. Biotechnol., 2025, 233

[208] Lan T, Que H, Luo M, Zhao X, Wei X. Genome editing via non-viral delivery platforms: current progress in personalized cancer therapy. Mol. Cancer, 2022, 21 71

[209] Wang Q, Guo F, Jin Y, Ma Y. Applications of human organoids in the personalized treatment for digestive diseases. Signal Transduct. Target. Ther., 2022, 7336

[210] Chen Y, Ping Y. Development of CRISPR/Cas delivery systems for in vivo precision genome editing. Acc. Chem. Res., 2023, 562185-2196

[211] Lo Y-H, et al. . Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions. Nat. Commun., 2025, 16 7566

[212] Li X, et al. . High-throughput microfluidic generation of self-assembled, uniform 3D vascularized and mineralized bone organoids without matrix biomaterials. Talanta Open, 2025, 12 100531

[213] Abilez OJ, et al. . Gastruloids enable modeling of the earliest stages of human cardiac and hepatic vascularization. Science, 2025, 388 eadu9375

[214] Miao Y, et al. . Co-development of mesoderm and endoderm enables organotypic vascularization in lung and gut organoids. Cell, 2025, 188: 4295-4313.e27

[215] Trompet D, Melis S, Chagin AS, Maes C. Skeletal stem and progenitor cells in bone development and repair. J. Bone Miner. Res., 2024, 39: 633-654

[216] Salhotra A, Shah HN, Levi B, Longaker MT. Mechanisms of bone development and repair. Nat. Rev. Mol. Cell Biol., 2020, 21: 696-711

[217] Quan H, et al. . Application of biomaterials in treating early osteonecrosis of the femoral head: research progress and future perspectives. Acta Biomater., 2023, 164: 15-73

[218] Qin Q, et al. . Neurovascular coupling in bone regeneration. Exp. Mol. Med., 2022, 54: 1844-1849

[219] Shao W, et al. . Inhibition of sympathetic tone via hypothalamic descending pathway propagates glucocorticoid-induced endothelial impairment and osteonecrosis of the femoral head. Bone Res., 2024, 12: 64

[220] Song S, et al. . Nerve–bone crosstalk manipulates bone organoid development and bone regeneration: a review and perspectives. Organoid Res., 2025, 18294

[221] Bohner M, Santoni BLG, Döbelin N. β-tricalcium phosphate for bone substitution: synthesis and properties. Acta Biomater., 2020, 11323-41

[222] Ye P, et al. . LL-37 and bisphosphonate co-delivery 3D-scaffold with antimicrobial and antiresorptive activities for bone regeneration. Int. J. Biol. Macromol., 2024, 277: 134091

[223] Chan SSL, Black JR, Franks GV, Heath DE. Hierarchically porous 3D-printed ceramic scaffolds for bone tissue engineering. Biomater. Adv., 2025, 169214149

[224] Wang W, et al. . Fused deposition modeling printed PLA/nano β-TCP composite bone tissue engineering scaffolds for promoting osteogenic induction function. Int. J. Nanomed., 2023, 185815-5830

[225] Tran DL, et al. . Optimized synthesis of biphasic calcium phosphate: enhancing bone regeneration with a tailored β-tricalcium phosphate/hydroxyapatite ratio. Biomater. Sci., 2025, 13: 969-979

[226] Wu Y, et al. . Core-shell structured porous calcium phosphate bioceramic spheres for enhanced bone regeneration. ACS Appl. Mater. Interfaces, 2022, 14: 47491-47506

[227] Krishna VS, et al. . Role of crosslinkers in advancing chitosan-based biocomposite scaffolds for bone tissue engineering: a comprehensive review. Int. J. Biol. Macromol., 2024, 283: 137625

[228] Guo L, et al. . The role of natural polymers in bone tissue engineering. J. Control. Release, 2021, 338571-582

[229] Zhang L, et al. . Multifunctional hydrogel/platelet-rich fibrin/nanofibers scaffolds with cell barrier and osteogenesis for guided tissue regeneration/guided bone regeneration applications. Int. J. Biol. Macromol., 2023, 253: 126960

[230] Liu Z, et al. . Calcium polyphosphate endows silk fibroin hydrogels with enhanced osteogenesis for bone function restoration. J. Mater. Chem. B, 2025, 1310331-10342

[231] Liu Y, et al. . Biomimetic fabrication of sr-silk fibroin co-assembly hydroxyapatite based microspheres with angiogenic and osteogenic properties for bone tissue engineering. Mater. Today Bio, 2024, 25 101011

[232] Bharathi R, et al. . Nuciferine-loaded chitosan hydrogel-integrated 3D-printed polylactic acid scaffolds for bone tissue engineering: a combinatorial approach. Int. J. Biol. Macromol., 2023, 253: 127492

[233] Francisco MJ, Cabral CSD, Ferreira P, Correia IJ, Moreira AF. Beeswax-enriched tricalcium phosphate/hydroxyapatite/sodium alginate/thymol 3D-printed scaffolds for application in bone tissue engineering. Biomater. Adv., 2026, 178214440

[234] Abu Elella MH, Kamel AM, López-Maldonado EA, Uzondu SW, Abdallah HM. A review of recent progress in alginate-based nanocomposite materials for tissue engineering applications. Int. J. Biol. Macromol., 2025, 297139840

[235] Mahmoud AH, et al. . Nanoscale β-TCP-laden GelMA/PCL composite membrane for guided bone regeneration. ACS Appl. Mater. Interfaces, 2023, 1532121-32135

[236] Golubchikov DO, Petrov AK, Popkov VA, Evdokimov PV, Putlayev VI. Advances in the fabrication of polycaprolactone-based composite scaffolds for bone tissue engineering: from chemical composition to scaffold architecture. ACS Biomater. Sci. Eng., 2025, 11: 3201-3227

[237] Li Y, et al. . Biomimetic 2D-oriented microporous PLLA scaffolds: fabrication and evaluation for bone repair. Int. J. Biol. Macromol., 2025, 311: 143918

[238] Zhou J, et al. . Enhanced healing of critical-sized bone defects using degradable scaffolds with tailored composition through immunomodulation and angiogenesis. Bioact. Mater., 2025, 44371-388

[239] Zhao D, et al. . Poly(lactic-co-glycolic acid)-based composite bone-substitute materials. Bioact. Mater., 2021, 6: 346-360

[240] Freeman FE, Stevens HY, Owens P, Guldberg RE, McNamara LM. Osteogenic differentiation of mesenchymal stem cells by mimicking the cellular niche of the endochondral template. Tissue Eng. Part A, 2016, 22: 1176-1190

[241] Freeman FE, Allen AB, Stevens HY, Guldberg RE, McNamara LM. Effects of in vitro endochondral priming and pre-vascularisation of human MSC cellular aggregates in vivo. Stem Cell Res. Ther., 2015, 6: 218

[242] Ahn J, et al. . 3D microfluidic bone tumor microenvironment comprised of hydroxyapatite/fibrin composite. Front. Bioeng. Biotechnol., 2019, 7168-180

[243] Das B, et al. . A vascularized bone-on-a-chip model development via exploring mechanical stimulation for evaluation of fracture healing therapeutics. In vitro Models, 2022, 1: 73-83

[244] Chen C, et al. . Biomimetic bone-vessel interface-on-a-chip for simulating periodontal physiological and pathological microenvironment. Regener. Biomater., 2025, 12: rbaf111

[245] Lee S, et al. . Bone-on-a-chip simulating bone metastasis in osteoporosis. Biofabrication, 2024, 1645025

[246] Mainardi A, et al. . Modular de- and re-construction of vascularized osteochondral tissues in an organ-on-chip dual-compartment platform. J. Orthop. Transl., 2026, 56101017

[247] Liu Q, et al. . Bone-on-leaf-chip for the study of lung cancer bone metastasis. Lab Chip, 2026, 261996-2011

[248] Hong JM, et al. . Genetic association of angiogenesis- and hypoxia-related gene polymorphisms with osteonecrosis of the femoral head. Exp. Mol. Med., 2010, 42: 376-385

[249] Asano T, et al. . ABCB1 C3435T and G2677T/A polymorphism decreased the risk for steroid-induced osteonecrosis of the femoral head after kidney transplantation. Pharmacogenetics, 2003, 13: 675-682

[250] Hao C, et al. . MiR-708 promotes steroid-induced osteonecrosis of femoral head, suppresses osteogenic differentiation by targeting SMAD3. Sci. Rep., 2016, 6 22599

[251] Yuan L, et al. . The relationship between genetic polymorphisms in apolipoprotein E (ApoE) gene and osteonecrosis of the femoral head induced by steroid in Chinese Han population. Genes Genom., 2018, 40: 225-231

[252] Song Y, et al. . Association of gene variants of transcription factors PPARγ, RUNX2, osterix genes and COL2A1, IGFBP3 genes with the development of osteonecrosis of the femoral head in Chinese population. Bone, 2017, 101: 104-112

[253] Samara S, et al. . Predictive role of cytokine gene polymorphisms for the development of femoral head osteonecrosis. Dis. Markers, 2012, 33: 215-221

[254] Liang X-Z, et al. . Identification of potential autophagy-related genes in steroid-induced osteonecrosis of the femoral head via bioinformatics analysis and experimental verification. J. Orthop. Surg. Res., 2022, 17: 86

[255] Zhang J, et al. . Screening of Potential Biomarkers in the Peripheral Serum for Steroid-Induced Osteonecrosis of the Femoral Head Based on WGCNA and Machine Learning Algorithms. Dis. Markers, 2022, 20222639470

[256] Chai J-L, et al. . Pyroptosis -related potential diagnostic biomarkers in steroid-induced osteonecrosis of the femoral head. BMC Musculoskelet. Disord., 2023, 24 609

[257] Lu H, et al. . Identification and validation of ferroptosis-related biomarkers in steroid-induced osteonecrosis of the femoral head. Int. Immunopharmacol., 2023, 124110906

[258] Wang Y, et al. . Integrative analysis of cellular autophagy-related genes in steroid-induced osteonecrosis of the femoral head. Am. J. Transl. Res., 2023, 155850-5872

[259] Luo H, et al. . Elucidating the role of the GC/GR/GLUT1 axis in steroid-induced osteonecrosis of the femoral head: a proteomic approach. Bone, 2024, 183 117074

[260] Wu T, et al. . Identification and validation of endoplasmic reticulum stress-related genes in patients with steroid-induced osteonecrosis of the femoral head. Sci. Rep., 2024, 14 21634

[261] Ma Z, et al. . Identification and analysis of mitochondria-related central genes in steroid-induced osteonecrosis of the femoral head, along with drug prediction. Front. Endocrinol., 2024, 151341366

Funding

National Natural Science Foundation of China (National Science Foundation of China)(82472439)

The General Program of Hubei Provincial Health Science and Technology Project (WJ2025M161)

Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)(2025AFB550)

RIGHTS & PERMISSIONS

The Author(s)