{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:23:48Z","timestamp":1790810628538,"version":"4.1.0"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>Hair follicle organoids (HF organoids) have progressed from simple epithelial\u2013mesenchymal aggregates to spatially organized follicle-like structures and skin\u2013hair follicle composite models. However, most current systems still focus on follicular morphogenesis and structural reconstruction, with limited capacity to recapitulate the immune, vascular, neural, and dynamic regulatory features of the native hair follicle (HF) microenvironment. This limitation is particularly relevant to immune-mediated hair disorders, such as alopecia areata, lichen planopilaris, and frontal fibrosing alopecia, in which immune privilege (IP) collapse, inflammatory infiltration, hair follicle stem cell (HFSC) niche damage, and tissue remodelling are central pathological events. In this Review, we discuss the transition from structurally oriented HF organoids towards immune-competent hair follicle microphysiological systems (HF-MPS). We summarize the structural basis of HF engineering, define immune competence as a functional state involving IP maintenance, immune-cell regulation of HF cycling and regeneration, and controllable inflammatory injury, and examine engineering strategies including local immune microenvironment control, compartmentalized culture, dynamic perfusion, vascularized and innervated interfaces, and quantitative monitoring. We further discuss applications in disease modelling, dynamic drug evaluation, patient-derived platforms, and regenerative medicine, while highlighting evidence boundaries and technical limitations. Immune-competent HF-MPS should be viewed as evolving human-relevant platforms rather than mature replacements for existing models.<\/jats:p>","DOI":"10.3389\/fbioe.2026.1846566","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:33:17Z","timestamp":1780896797000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Engineering immune-competent hair follicle microphysiological systems: from organoid assembly to dynamic immune modelling"],"prefix":"10.3389","volume":"14","author":[{"given":"Hanxiao","family":"Qu","sequence":"first","affiliation":[{"name":"Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liudong","family":"Tong","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyi","family":"Lou","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Qing","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maocan","family":"Tao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbin","family":"Luo","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5301","DOI":"10.1038\/s41467-018-07579-y","article-title":"Tissue engineering of human hair follicles using a biomimetic developmental approach","volume":"9","author":"Abaci","year":"2018","journal-title":"Nat. Commun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e10235","DOI":"10.1002\/btm2.10235","article-title":"Recreation of a hair follicle regenerative microenvironment: successes and pitfalls","volume":"7","author":"Abreu","year":"2022","journal-title":"Bioeng. and Transla Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1038\/s41467-023-37187-4","article-title":"Modeling of three-dimensional innervated epidermal like-layer in a microfluidic chip-based coculture system","volume":"14","author":"Ahn","year":"2023","journal-title":"Nat. Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.cell.2017.05.002","article-title":"Regulatory T cells in skin facilitate epithelial stem cell differentiation","volume":"169","author":"Ali","year":"2017","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1039\/c3lc50227a","article-title":"Skin and hair on-a-chip: in vitro skin models versus ex vivo tissue maintenance with dynamic perfusion","volume":"13","author":"Ata\u00e7","year":"2013","journal-title":"Lab. Chip"},{"key":"B6","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1111\/exd.14155","article-title":"Hair follicle immune privilege and its collapse in alopecia areata","volume":"29","author":"Bertolini","year":"2020","journal-title":"Exp. Dermatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1039\/D5LC00867K","article-title":"An in vitro organ-on-chip model for studying neuron\u2013keratinocyte interactions in sensory response through electrophysiology","volume":"26","author":"Bessy","year":"2026","journal-title":"Lab. Chip"},{"key":"B8","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3390\/organoids2030011","article-title":"Incorporating immune cells into organoid models: essential for studying human disease","volume":"2","author":"Bogoslowski","year":"2023","journal-title":"Organoids"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3561","DOI":"10.3390\/cancers14153561","article-title":"Engineered microphysiological systems for testing effectiveness of cell-based cancer immunotherapies","volume":"14","author":"Campisi","year":"2022","journal-title":"Cancers"},{"key":"B10","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1093\/toxsci\/kfae122","article-title":"An industry perspective on the FDA modernization act 2.0\/3.0: potential next steps for sponsors to reduce animal use in drug development","volume":"203","author":"Carratt","year":"2025","journal-title":"Toxicol. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e1002002","DOI":"10.1371\/journal.pbio.1002002","article-title":"Macrophages contribute to the cyclic activation of adult hair follicle stem cells","volume":"12","author":"Castellana","year":"2014","journal-title":"PLOS Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1093\/stcltm\/szac059","article-title":"The emergent power of human cellular vs mouse models in translational hair research","volume":"11","author":"Castro","year":"2022","journal-title":"Stem Cells Transl. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s12951-021-00840-5","article-title":"Nanoscale microenvironment engineering for expanding human hair follicle stem cell and revealing their plasticity","volume":"19","author":"Chen","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"129934","DOI":"10.1016\/j.ijbiomac.2024.129934","article-title":"Biomimetic biphasic microsphere preparation based on the thermodynamic incompatibility of glycosaminoglycan with gelatin methacrylate for hair regeneration","volume":"261","author":"Chen","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.bpj.2022.11.2943","article-title":"Predicting YAP\/TAZ nuclear translocation in response to ECM mechanosensing","volume":"122","author":"Cheng","year":"2023","journal-title":"Biophys. J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"13683","DOI":"10.1021\/acsnano.1c04958","article-title":"Nanosensor chemical cytometry for characterizing the efflux heterogeneity of nitric oxide from macrophages","volume":"15","author":"Cho","year":"2021","journal-title":"ACS Nano"},{"key":"B17","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/3-540-29937-8_5","article-title":"Modeling cell-mediated immunity by means of P systems","volume-title":"Applications of Membrane Computing","author":"Ciobanu","year":"2005"},{"key":"B18","doi-asserted-by":"publisher","first-page":"eadh0152","DOI":"10.1126\/sciimmunol.adh0152","article-title":"Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche","volume":"9","author":"Cohen","year":"2024","journal-title":"Sci. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1021\/acsnano.1c08728","article-title":"Biomaterial-mediated presentation of jagged-1 mimetic ligand enhances cellular activation of notch signaling and bone regeneration","volume":"16","author":"Deng","year":"2022","journal-title":"ACS Nano"},{"key":"B20","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/s41392-023-01501-9","article-title":"Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets","volume":"8","author":"Di","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1039\/D1LC00689D","article-title":"Microfluidic organ-on-chip system for multi-analyte monitoring of metabolites in 3D cell cultures","volume":"22","author":"Dornhof","year":"2022","journal-title":"Lab. Chip"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.3390\/polym12122784","article-title":"Preliminary study of in vitro three-dimensional skin model using an ovine collagen type I sponge seeded with Co-culture skin cells: submerged versus air-liquid interface conditions","volume":"12","author":"Fauzi","year":"2020","journal-title":"Polymers"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.3390\/ijms20071741","article-title":"Sustained human hair follicle growth ex vivo in a glycosaminoglycan hydrogel matrix","volume":"20","author":"Fern\u00e1ndez-Martos","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.bioactmat.2023.06.004","article-title":"Recent advances in defined hydrogels in organoid research","volume":"28","author":"Gan","year":"2023","journal-title":"Bioact. Mat."},{"key":"B25","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.molimm.2021.02.021","article-title":"Dermal macrophage and its potential in inducing hair follicle regeneration","volume":"134","author":"Gao","year":"2021","journal-title":"Mol. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s00441-004-0925-3","article-title":"Vascular adhesion and transendothelial migration of eosinophil leukocytes","volume":"318","author":"Gonlugur","year":"2004","journal-title":"Cell Tissue Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1146\/annurev-immunol-101721-062818","article-title":"Immune-epithelial cross talk in regeneration and repair","volume":"41","author":"Guenin-Mace","year":"2023","journal-title":"Annu. Rev. Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3390\/cells14010007","article-title":"Hair regeneration methods using cells derived from human hair follicles and challenges to overcome","volume":"14","author":"Hamida","year":"2024","journal-title":"Cells"},{"key":"B29","doi-asserted-by":"publisher","first-page":"809","DOI":"10.3390\/toxics12110809","article-title":"Development of a novel microphysiological system for peripheral neurotoxicity prediction using human iPSC-derived neurons with morphological deep learning","volume":"12","author":"Han","year":"2024","journal-title":"Toxics"},{"key":"B30","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.molmed.2018.03.007","article-title":"Lichen planopilaris and frontal fibrosing alopecia as model epithelial stem cell diseases","volume":"24","author":"Harries","year":"2018","journal-title":"Trends Mol. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2953","DOI":"10.3390\/cells11192953","article-title":"Macrophage-mediated inflammation in skin wound healing","volume":"11","author":"Hassanshahi","year":"2022","journal-title":"Cells"},{"key":"B32","doi-asserted-by":"publisher","first-page":"19679","DOI":"10.1073\/pnas.1309970110","article-title":"Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth","volume":"110","author":"Higgins","year":"2013","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1039\/D3LC00719G","article-title":"Self-assembled and perfusable microvasculature-on-chip for modeling leukocyte trafficking","volume":"24","author":"Hirth","year":"2024","journal-title":"Lab. Chip"},{"key":"B34","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s40779-023-00475-7","article-title":"Bioengineered skin organoids: from development to applications","volume":"10","author":"Hong","year":"2023","journal-title":"Mil. Med. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"773","DOI":"10.3390\/cimb47090773","article-title":"Insulin-like growth factor 1 (IGF-1) in hair regeneration: mechanistic pathways and therapeutic potential","volume":"47","author":"Hsieh","year":"2025","journal-title":"CIMB"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2805","DOI":"10.1016\/j.jid.2024.05.022","article-title":"Essential role of macrophages in contact hypersensitivity\u2013induced hair regeneration","volume":"144","author":"Huang","year":"2024","journal-title":"J. Invest. Dermatol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jdermsci.2010.09.006","article-title":"Hair follicle is a target of stress hormone and autoimmune reactions","volume":"60","author":"Ito","year":"2010","journal-title":"J. Dermatological Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/S0002-9440(10)63151-3","article-title":"Collapse and restoration of MHC class-I-dependent immune privilege","volume":"164","author":"Ito","year":"2004","journal-title":"Am. J. Pathol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"116683","DOI":"10.1016\/j.bios.2024.116683","article-title":"Organ chips with integrated multifunctional sensors enable continuous metabolic monitoring at controlled oxygen levels","volume":"265","author":"Izadifar","year":"2024","journal-title":"Biosens. Bioelectron."},{"key":"B40","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/s41392-024-01880-7","article-title":"Sensory neurons: unveiling the symphony of wound healing","volume":"9","author":"Jiang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"B41","doi-asserted-by":"publisher","first-page":"eadd4603","DOI":"10.1126\/sciadv.add4603","article-title":"Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction","volume":"8","author":"Kageyama","year":"2022","journal-title":"Sci. Adv."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/9271869","article-title":"Hair germ model in vitro via human postnatal keratinocyte-dermal papilla interactions: impact of hyaluronic acid","volume":"2017","author":"Kalabusheva","year":"2017","journal-title":"Stem Cells Int."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e202200620","DOI":"10.1002\/asia.202200620","article-title":"3D printing of skin equivalents with hair follicle structures and epidermal-papillary-dermal layers using gelatin\/hyaluronic acid hydrogels","volume":"17","author":"Kang","year":"2022","journal-title":"Chem. \u2013 Asian J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1900513","DOI":"10.1002\/advs.201900513","article-title":"Exosome-guided phenotypic switch of M1 to M2 macrophages for cutaneous wound healing","volume":"6","author":"Kim","year":"2019","journal-title":"Adv. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1093\/bioinformatics\/btz610","article-title":"VirtualCytometry: a webserver for evaluating immune cell differentiation using single-cell RNA sequencing data","volume":"36","author":"Kim","year":"2020","journal-title":"Bioinformatics"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.3390\/cells13231991","article-title":"Transcriptomic analysis of air\u2013liquid interface culture in human lung organoids reveals regulators of epithelial differentiation","volume":"13","author":"Kim","year":"2024","journal-title":"Cells"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1397067","DOI":"10.3389\/fphys.2024.1397067","article-title":"Immune niches for hair follicle development and homeostasis","volume":"15","author":"Kiselev","year":"2024","journal-title":"Front. Physiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2303161","DOI":"10.1002\/adhm.202303161","article-title":"Patient-derived microphysiological systems for precision medicine","volume":"13","author":"Ko","year":"2024","journal-title":"Adv. Healthc. Mat."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2041731417724640","DOI":"10.1177\/2041731417724640","article-title":"Design of biomimetic cellular scaffolds for co-culture system and their application","volume":"8","author":"Kook","year":"2017","journal-title":"J. Tissue Eng."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1007\/s11517-024-03062-7","article-title":"Advances and challenges in organ-on-chip technology: toward mimicking human physiology and disease in vitro","volume":"62","author":"Kumar","year":"2024","journal-title":"Med. Biol. Eng. Comput."},{"key":"B51","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/s12276-023-01151-5","article-title":"Deciphering the molecular mechanisms of stem cell dynamics in hair follicle regeneration","volume":"56","author":"Lee","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41586-020-2352-3","article-title":"Hair-bearing human skin generated entirely from pluripotent stem cells","volume":"582","author":"Lee","year":"2020","journal-title":"Nature"},{"key":"B53","doi-asserted-by":"publisher","first-page":"114866","DOI":"10.1016\/j.addr.2023.114866","article-title":"Air-liquid interface cultures to model drug delivery through the mucociliary epithelial barrier","volume":"198","author":"Lee","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B54","doi-asserted-by":"publisher","first-page":"101216","DOI":"10.1016\/j.pmatsci.2023.101216","article-title":"Engineered biomimetic hydrogels for organoids","volume":"141","author":"Li","year":"2024","journal-title":"Prog. Mater. Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"899095","DOI":"10.3389\/fcell.2022.899095","article-title":"Morphogenesis, growth cycle and molecular regulation of hair follicles","volume":"10","author":"Lin","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/s41586-024-07237-y","article-title":"CGRP sensory neurons promote tissue healing via neutrophils and macrophages","volume":"628","author":"Lu","year":"2024","journal-title":"Nature"},{"key":"B57","doi-asserted-by":"publisher","first-page":"863786","DOI":"10.3389\/fmed.2022.863786","article-title":"Epithelial-mesenchymal interaction in hair regeneration and skin wound healing","volume":"9","author":"Mao","year":"2022","journal-title":"Front. Med."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1195858","DOI":"10.3389\/fimmu.2023.1195858","article-title":"The evaluation of JAK inhibitors on effect and safety in alopecia areata: a systematic review and meta-analysis of 2018 patients","volume":"14","author":"Mao","year":"2023","journal-title":"Front. Immunol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"5001","DOI":"10.3390\/ijms24055001","article-title":"Molecular mechanisms of neurogenic inflammation of the skin","volume":"24","author":"Marek-Jozefowicz","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1007\/s00396-020-04601-y","article-title":"Janus particles: from concepts to environmentally friendly materials and sustainable applications","volume":"298","author":"Marschelke","year":"2020","journal-title":"Colloid Polym. Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"8861","DOI":"10.1038\/s41598-023-34796-3","article-title":"Design and evaluation of a skin-on-a-chip pumpless microfluidic device","volume":"13","author":"Mohamadali","year":"2023","journal-title":"Sci. Rep."},{"key":"B62","doi-asserted-by":"publisher","first-page":"615","DOI":"10.3390\/pharmaceutics16050615","article-title":"Organ-on-a-chip: ubi sumus? Fundamentals and design aspects","volume":"16","author":"Morais","year":"2024","journal-title":"Pharmaceutics"},{"key":"B63","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.biomaterials.2016.11.031","article-title":"Skin integrated with perfusable vascular channels on a chip","volume":"116","author":"Mori","year":"2017","journal-title":"Biomaterials"},{"key":"B64","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/s41592-022-01435-0","article-title":"Unraveling immune cell behavior","volume":"19","author":"Mukhopadhyay","year":"2022","journal-title":"Nat. Methods"},{"key":"B65","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/s41551-024-01236-0","article-title":"Standardizing designed and emergent quantitative features in microphysiological systems","volume":"8","author":"Nahon","year":"2024","journal-title":"Nat. Biomed. Eng."},{"key":"B66","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nmeth1012","article-title":"The development of a bioengineered organ germ method","volume":"4","author":"Nakao","year":"2007","journal-title":"Nat. Methods"},{"key":"B67","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.cell.2015.11.058","article-title":"WNT-SHH antagonism specifies and expands stem cells prior to niche formation","volume":"164","author":"Ouspenskaia","year":"2016","journal-title":"Cell"},{"key":"B68","doi-asserted-by":"publisher","first-page":"101","DOI":"10.2165\/00128071-200001020-00004","article-title":"Alopecia areata: pathogenesis, diagnosis, and therapy","volume":"1","author":"Papadopoulos","year":"2000","journal-title":"Am. J. Clin. Dermatol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1093\/cei\/uxae004","article-title":"Revolutionizing immune research with organoid-based co-culture and chip systems","volume":"218","author":"Papp","year":"2024","journal-title":"Clin. Exp. Immunol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"933370","DOI":"10.3389\/fcell.2022.933370","article-title":"Hair follicle morphogenesis during embryogenesis, neogenesis, and organogenesis","volume":"10","author":"Park","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1046\/j.1365-2133.1996.d01-1099.x","article-title":"Effects of interleukins, colony-stimulating factor and tumour necrosis factor on human hair follicle growth in vitro: a possible role for interleukin-1 and tumour necrosis factor-\u03b1 in alopecia areata","volume":"135","author":"Philpott","year":"1996","journal-title":"Br. J. Dermatol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"856","DOI":"10.3390\/cells9040856","article-title":"Macrophage-derived extracellular vesicle promotes hair growth","volume":"9","author":"Rajendran","year":"2020","journal-title":"Cells"},{"key":"B73","doi-asserted-by":"publisher","first-page":"565","DOI":"10.3390\/mi11060565","article-title":"OOCHIP: compartmentalized microfluidic perfusion system with porous barriers for enhanced cell\u2013cell crosstalk in organ-on-a-chip","volume":"11","author":"Ramadan","year":"2020","journal-title":"Micromachines"},{"key":"B74","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1111\/j.0022-202X.2004.23461.x","article-title":"Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance?","volume":"123","author":"Rosenblum","year":"2004","journal-title":"J. Invest. Dermatol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"115057","DOI":"10.1016\/j.bios.2022.115057","article-title":"Integrated technologies for continuous monitoring of organs-on-chips: current challenges and potential solutions","volume":"224","author":"Sabat\u00e9 Del R\u00edo","year":"2023","journal-title":"Biosens. Bioelectron."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/bit.70229","article-title":"Microphysiological systems: transforming biomedical and clinical research","author":"Sahoo","year":"2026","journal-title":"Biotechnol. Bioeng. Bit."},{"key":"B77","doi-asserted-by":"publisher","first-page":"R132","DOI":"10.1016\/j.cub.2008.12.005","article-title":"The hair follicle as a dynamic miniorgan","volume":"19","author":"Schneider","year":"2009","journal-title":"Curr. Biol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1089\/ars.2005.7.1249","article-title":"Mechanisms of monocyte recruitment in vascular repair after injury","volume":"7","author":"Schober","year":"2005","journal-title":"Antioxid. Redox Signal."},{"key":"B79","doi-asserted-by":"publisher","first-page":"100113","DOI":"10.1016\/j.xjidi.2022.100113","article-title":"Frontiers in lichen planopilaris and frontal fibrosing alopecia research: pathobiology progress and translational Horizons","volume":"2","author":"Senna","year":"2022","journal-title":"JID Innov."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1805170","DOI":"10.3389\/fmed.2026.1805170","article-title":"Hair follicle immune privilege in autoimmune and immune-mediated alopecias: paths toward reestablishing immune tolerance","volume":"13","author":"Shafiei-Jahani","year":"2026","journal-title":"Front. Med."},{"key":"B81","doi-asserted-by":"publisher","first-page":"100994","DOI":"10.1016\/j.dmpk.2023.100994","article-title":"Air\u2013liquid interface culture and modified culture medium promote the differentiation of human induced pluripotent stem cells into intestinal epithelial cells","volume":"55","author":"Shirai","year":"2024","journal-title":"Drug Metab. Pharmacokinet."},{"key":"B82","doi-asserted-by":"publisher","first-page":"eadu5905","DOI":"10.1126\/sciadv.adu5905","article-title":"3D bioprinting of collagen-based high-resolution internally perfusable scaffolds for engineering fully biologic tissue systems","volume":"11","author":"Shiwarski","year":"2025","journal-title":"Sci. Adv."},{"key":"B83","doi-asserted-by":"publisher","first-page":"100187","DOI":"10.1016\/j.dmd.2025.100187","article-title":"Microphysiological systems as an emerging in vitro approach for the evaluation of drug absorption, distribution, metabolism, and excretion and toxicity","volume":"53","author":"Shrimali","year":"2025","journal-title":"Drug Metab. Dispos."},{"key":"B84","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s40257-024-00899-4","article-title":"Patient-reported hair loss and its impacts as measured by the alopecia areata patient priority outcomes instrument in patients treated with ritlecitinib: the ALLEGRO phase 2b\/3 randomized clinical trial","volume":"26","author":"Sinclair","year":"2025","journal-title":"Am. J. Clin. Dermatol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1152\/physrev.2001.81.1.449","article-title":"Controls of hair follicle cycling","volume":"81","author":"Stenn","year":"2001","journal-title":"Physiol. Rev."},{"key":"B86","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1021\/acsbiomaterials.3c01346","article-title":"Large-scale preparation of hair follicle germs using a microfluidic device","volume":"10","author":"Sugiyama","year":"2024","journal-title":"ACS Biomater. Sci. Eng."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1801363","DOI":"10.1002\/adhm.201801363","article-title":"Organ-on-a-chip for cancer and immune organs modeling","volume":"8","author":"Sun","year":"2019","journal-title":"Adv. Healthc. Mat."},{"key":"B88","doi-asserted-by":"publisher","first-page":"5481","DOI":"10.1038\/s41467-022-33114-1","article-title":"Modeling human HSV infection via a vascularized immune-competent skin-on-chip platform","volume":"13","author":"Sun","year":"2022","journal-title":"Nat. Commun."},{"key":"B89","doi-asserted-by":"publisher","first-page":"7","DOI":"10.33696\/immunology.6.187","article-title":"Hair follicle stem cells: the signaling hub of the skin","volume":"6","author":"Tan","year":"2024","journal-title":"J. Cell. Immunol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"214423","DOI":"10.1016\/j.bioadv.2025.214423","article-title":"Comparative analysis of 3D and 2D cell-culturing methods in hair follicle spheroid morphogenesis and drug responsiveness","volume":"177","author":"Tan","year":"2025","journal-title":"Biomater. Adv."},{"key":"B91","doi-asserted-by":"publisher","first-page":"e21463","DOI":"10.1096\/fj.202002590RRR","article-title":"Organ-on-chip of the cervical epithelial layer: a platform to study normal and pathological cellular remodeling of the cervix","volume":"35","author":"Tantengco","year":"2021","journal-title":"FASEB J."},{"key":"B92","doi-asserted-by":"publisher","first-page":"2301868","DOI":"10.1002\/advs.202301868","article-title":"Generation of human endometrial assembloids with a luminal epithelium using air\u2013liquid interface culture methods","volume":"10","author":"Tian","year":"2023","journal-title":"Adv. Sci."},{"key":"B93","doi-asserted-by":"publisher","first-page":"1191104","DOI":"10.3389\/fbioe.2023.1191104","article-title":"Integration of immune cells in organs-on-chips: a tutorial","volume":"11","author":"Van Os","year":"","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"106485","DOI":"10.1016\/j.ejps.2023.106485","article-title":"Immune cell extravasation in an organ-on-chip to model lung inflammation","volume":"187","author":"Van Os","year":"","journal-title":"Eur. J. Pharm. Sci."},{"key":"B95","doi-asserted-by":"publisher","first-page":"1600773","DOI":"10.1002\/adhm.201600773","article-title":"Multicomponent injectable hydrogels for antigen-specific tolerogenic immune modulation","volume":"6","author":"Verbeke","year":"2017","journal-title":"Adv. Healthc. Mat."},{"key":"B96","doi-asserted-by":"publisher","first-page":"14091","DOI":"10.1038\/ncomms14091","article-title":"Macrophages induce AKT\/\u03b2-catenin-dependent Lgr5+ stem cell activation and hair follicle regeneration through TNF","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun."},{"key":"B97","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1016\/j.apsb.2023.02.006","article-title":"Emerging trends in organ-on-a-chip systems for drug screening","volume":"13","author":"Wang","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"B98","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1089\/ars.2020.8195","article-title":"The impact of oxygen availability and multilineage communication on organoid maturation","volume":"35","author":"W\u00f6rsd\u00f6rfer","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"B99","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.reth.2022.11.003","article-title":"Cells, growth factors and biomaterials used in tissue engineering for hair follicles regeneration","volume":"21","author":"Xu","year":"2022","journal-title":"Regen. Ther."},{"key":"B100","doi-asserted-by":"publisher","first-page":"158","DOI":"10.14715\/cmb\/2024.70.4.25","article-title":"Injectable platelet-rich fibrin promotes proliferation and trichogenic inductivity of dermal papilla cells through activating TGF-\u03b2\/Smad signaling pathway","volume":"70","author":"Xu","year":"2024","journal-title":"Cell Mol. Biol. (Noisy-le-grand)"},{"key":"B101","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/s41580-023-00662-3","article-title":"Local and systemic mechanisms that control the hair follicle stem cell niche","volume":"25","author":"Zhang","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B102","doi-asserted-by":"publisher","first-page":"6950","DOI":"10.1007\/s12035-024-03980-5","article-title":"Photobiomodulation increases M2-type polarization of macrophages by inhibiting versican production after spinal cord injury","volume":"61","author":"Zhang","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.bioactmat.2025.09.021","article-title":"Dynamic hydrogel mechanics in organoid engineering: from matrix design to translational paradigms","volume":"55","author":"Zhang","year":"2026","journal-title":"Bioact. Mat."},{"key":"B104","doi-asserted-by":"publisher","first-page":"637048","DOI":"10.3389\/fbioe.2021.637048","article-title":"Review on the vascularization of organoids and organoids-on-a-chip","volume":"9","author":"Zhao","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1093\/toxsci\/kfad093","article-title":"The frontline of alternatives to animal testing: novel in vitro skin model application in drug development and evaluation","volume":"196","author":"Zhao","year":"2023","journal-title":"Toxicol. Sci."},{"key":"B106","doi-asserted-by":"publisher","first-page":"1621492","DOI":"10.3389\/fimmu.2025.1621492","article-title":"From mechanisms to therapies: current advances breakthroughs in alopecia areata immunopathology","volume":"16","author":"Zhao","year":"2025","journal-title":"Front. Immunol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"3608","DOI":"10.1039\/D1TB00107H","article-title":"Biomaterial-based physical regulation of macrophage behaviour","volume":"9","author":"Zhou","year":"2021","journal-title":"J. Mat. Chem. B"},{"key":"B108","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.jare.2024.05.006","article-title":"Crosstalk between endothelial cells and dermal papilla entails hair regeneration and angiogenesis during aging","volume":"70","author":"Zhou","year":"2025","journal-title":"J. Adv. Res."}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2026.1846566\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:33:18Z","timestamp":1780896798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2026.1846566\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":108,"alternative-id":["10.3389\/fbioe.2026.1846566"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2026.1846566","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]},"article-number":"1846566"}}