{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:40:46Z","timestamp":1791330046877,"version":"4.3.1"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"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>\n                    Several cartilage and bone organoids have been developed\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    using adult mesenchymal stromal\/stem cells (MSCs) or pluripotent stem cells (PSCs) to mimic different phases of endochondral ossification (ECO), as one of the main processes driving skeletal development and growth. While cellular and molecular features of growth plate-like structures have been observed through the generation and\n                    <jats:italic>in vivo<\/jats:italic>\n                    implantation of hypertrophic cartilage tissues, no functional analogue or model of the growth plate has yet been engineered. Herein, after a brief introduction about the growth plate architecture and function, we summarize the recent progress in dissecting the biology of the growth plate and indicate the knowledge gaps to better understand the mechanisms of its development and maintenance. We then discuss how this knowledge could be integrated with state-of-art bioengineering approaches to generate a functional\n                    <jats:italic>in vitro<\/jats:italic>\n                    growth plate model.\n                  <\/jats:p>","DOI":"10.3389\/fbioe.2025.1550713","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T02:10:21Z","timestamp":1741054221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Challenges of engineering a functional growth plate in vitro"],"prefix":"10.3389","volume":"13","author":[{"given":"Gangyu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Moya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Scherberich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1210\/endo.143.5.8776","article-title":"The role of the resting zone in growth plate chondrogenesis","volume":"143","author":"Abad","year":"2002","journal-title":"Endocrinology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"12025","DOI":"10.1073\/pnas.192291499","article-title":"Engineering growing tissues","volume":"99","author":"Alsberg","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B3","doi-asserted-by":"publisher","first-page":"14794","DOI":"10.1073\/pnas.0405091101","article-title":"Stimulatory G protein directly regulates hypertrophic differentiation of growth plate cartilage in vivo","volume":"101","author":"Bastepe","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B4","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/nm.3028","article-title":"The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine","volume":"19","author":"Bianco","year":"2013","journal-title":"Nat. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1242\/dev.102210","article-title":"Skeletal stem cells","volume":"142","author":"Bianco","year":"2015","journal-title":"Development"},{"key":"B6","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1002\/jor.1100090504","article-title":"Mesenchymal stem cells","volume":"9","author":"Caplan","year":"1991","journal-title":"J. Orthop. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.2106\/00004623-198365080-00005","article-title":"Salter-Harris Type-IV injuries of the distal tibial epiphyseal growth plate, with emphasis on those involving the medial malleolus","volume":"65","author":"Cass","year":"1983","journal-title":"J. Bone Jt. Surg. Am."},{"key":"B8","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1182\/blood.v56.2.289.289","article-title":"Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny","volume":"56","author":"Castro-Malaspina","year":"1980","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.cell.2014.12.002","article-title":"Identification and specification of the mouse skeletal stem cell","volume":"160","author":"Chan","year":"2015","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.cell.2018.07.029","article-title":"Identification of the human skeletal stem cell","volume":"175","author":"Chan","year":"2018","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/nmat4489","article-title":"Hydrogels with tunable stress relaxation regulate stem cell fate and activity","volume":"15","author":"Chaudhuri","year":"2016","journal-title":"Nat. Mater"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1093\/icb\/icz082","article-title":"Developmental and evolutionary allometry of the mammalian limb skeleton","volume":"59","author":"Cooper","year":"2019","journal-title":"Integr. Comp. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/nbt.3210","article-title":"Generation of articular chondrocytes from human pluripotent stem cells","volume":"33","author":"Craft","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1038\/nri.2017.53","article-title":"Adult haematopoietic stem cell niches","volume":"17","author":"Crane","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/nmat4483","article-title":"Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels","volume":"15","author":"Das","year":"2016","journal-title":"Nat. Mater"},{"key":"B16","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1002\/jbmr.4524","article-title":"Differentiation of induced pluripotent stem cells into chondrocytes: methods and applications for disease modeling and drug discovery","volume":"37","author":"De Kinderen","year":"2022","journal-title":"J. Bone Min. Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"B18","doi-asserted-by":"publisher","first-page":"105102","DOI":"10.1016\/j.jmbbm.2022.105102","article-title":"The heterogeneous mechanical properties of adolescent growth plate cartilage: a study in rabbit","volume":"128","author":"Eckstein","year":"2022","journal-title":"J. Mech. Behav. Biomed. Mater"},{"key":"B19","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1471-2474-12-31","article-title":"In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells","volume":"12","author":"Farrell","year":"2011","journal-title":"BMC Musculoskelet. Disord."},{"key":"B20","doi-asserted-by":"publisher","first-page":"111013","DOI":"10.1016\/j.jbiomech.2022.111013","article-title":"Material properties and strain distribution patterns of bovine growth plate cartilage vary with anatomic location and depth","volume":"134","author":"Fischenich","year":"2022","journal-title":"J. Biomech."},{"key":"B21","doi-asserted-by":"publisher","first-page":"eabb5093","DOI":"10.1126\/sciadv.abb5093","article-title":"3D bioprinting spatiotemporally defined patterns of growth factors to tightly control tissue regeneration","volume":"6","author":"Freeman","year":"2020","journal-title":"Sci. Adv."},{"key":"B22","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1242\/dev.16.3.381","article-title":"Osteogenesis in transplants of bone marrow cells","volume":"16","author":"Friedenstein","year":"1966","journal-title":"J. Embryol. Exp. Morphol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"105808","DOI":"10.1016\/j.isci.2022.105808","article-title":"Deciphering postnatal limb development at single-cell resolution","volume":"26","author":"Gao","year":"2023","journal-title":"iScience"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3431","DOI":"10.1002\/elps.201100237","article-title":"A simple elastic membrane-based microfluidic chip for the proliferation and differentiation of mesenchymal stem cells under tensile stress","volume":"32","author":"Gao","year":"2011","journal-title":"Electrophoresis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.bbrc.2009.08.072","article-title":"Effects of cyclic stretch on proliferation of mesenchymal stem cells and their differentiation to smooth muscle cells","volume":"388","author":"Ghazanfari","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1096\/fj.07-087924","article-title":"Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs)","volume":"22","author":"Gong","year":"2008","journal-title":"Faseb J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e6067","DOI":"10.1371\/journal.pone.0006067","article-title":"The wnt\/\u03b2-catenin pathway interacts differentially with PTHrP signaling to control chondrocyte hypertrophy and final maturation","volume":"4","author":"Guo","year":"2009","journal-title":"PLoS One"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e64513","DOI":"10.7554\/elife.64513","article-title":"Chondrocytes in the resting zone of the growth plate are maintained in a Wnt-inhibitory environment","volume":"10","author":"Hallett","year":"2021","journal-title":"Elife"},{"key":"B29","doi-asserted-by":"publisher","first-page":"6009","DOI":"10.3390\/ijms20236009","article-title":"Growth Plate chondrocytes: skeletal development, growth and beyond","volume":"20","author":"Hallett","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1038\/s41422-021-00467-z","article-title":"Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses","volume":"31","author":"He","year":"2021","journal-title":"Cell Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"9924","DOI":"10.1074\/jbc.m112.409342","article-title":"Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium","volume":"288","author":"Hojo","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1242\/dev.01564","article-title":"Sequential roles of Hedgehog and Wnt signaling in osteoblast development","volume":"132","author":"Hu","year":"2005","journal-title":"Development"},{"key":"B33","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1634\/stemcells.22-3-313","article-title":"Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells","volume":"22","author":"Huang","year":"2004","journal-title":"Stem Cells"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1038\/nmat4407","article-title":"Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation","volume":"14","author":"Huebsch","year":"2015","journal-title":"Nat. Mater"},{"key":"B35","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1097\/00003086-200004000-00006","article-title":"Epiphyseal plate involvement in osteosarcoma","volume":"373","author":"Jesus-Garcia","year":"2000","journal-title":"Clin. Orthop. Relat. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1046\/j.1365-2443.1999.00250.x","article-title":"Developmental patterning in chondrocytic cultures by morphogenic gradients: BMP induces expression of indian hedgehog and noggin","volume":"4","author":"Kameda","year":"1999","journal-title":"Genes cells."},{"key":"B37","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nature01657","article-title":"Developmental regulation of the growth plate","volume":"423","author":"Kronenberg","year":"2003","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e2211510120","DOI":"10.1073\/pnas.2211510120","article-title":"Modeling human skeletal development using human pluripotent stem cells","volume":"120","author":"Lamande","year":"2023","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1016\/j.celrep.2016.04.043","article-title":"Systematic reconstruction of molecular cascades regulating GP development using single-cell RNA-seq","volume":"15","author":"Li","year":"2016","journal-title":"Cell Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41413-022-00235-8","article-title":"Insights into skeletal stem cells","volume":"10","author":"Li","year":"2022","journal-title":"Bone Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.cell.2016.06.011","article-title":"Mapping the pairwise choices leading from pluripotency to human bone, heart, and other mesoderm cell types","volume":"166","author":"Loh","year":"2016","journal-title":"Cell."},{"key":"B42","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.biocel.2007.06.009","article-title":"Endochondral ossification: how cartilage is converted into bone in the developing skeleton","volume":"40","author":"Mackie","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1530\/joe-11-0048","article-title":"The skeleton: a multi-functional complex organ: the growth plate chondrocyte and endochondral ossification","volume":"211","author":"Mackie","year":"2011","journal-title":"J. Endocrinol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1002\/adhm.201300263","article-title":"Microfluidic generation of gradient hydrogels to modulate hematopoietic stem cell culture environment","volume":"3","author":"Mahadik","year":"2014","journal-title":"Adv. Healthc. Mater"},{"key":"B45","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/s41586-020-2144-9","article-title":"Recapitulating the human segmentation clock with pluripotent stem cells","volume":"580","author":"Matsuda","year":"2020","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/s41556-020-0567-z","article-title":"Cellular and molecular architecture of the intestinal stem cell niche","volume":"22","author":"McCarthy","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.stem.2009.05.008","article-title":"Home at last: neural stem cell niches defined","volume":"4","author":"Miller","year":"2009","journal-title":"Cell Stem Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1038\/nmat3357","article-title":"Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues","volume":"11","author":"Miller","year":"2012","journal-title":"Nat. Mater"},{"key":"B49","doi-asserted-by":"publisher","first-page":"4523","DOI":"10.1242\/dev.128.22.4523","article-title":"BMP and Ihh\/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation","volume":"128","author":"Minina","year":"2001","journal-title":"Development"},{"key":"B50","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/s41586-018-0662-5","article-title":"Resting zone of the growth plate houses a unique class of skeletal stem cells","volume":"563","author":"Mizuhashi","year":"2018","journal-title":"Nature"},{"key":"B51","doi-asserted-by":"publisher","first-page":"224","DOI":"10.22203\/ecm.v024a16","article-title":"Interleukin-1\u03b2 modulates endochondral ossification by human adult bone marrow stromal cells","volume":"24","author":"Mumme","year":"2012","journal-title":"Eur. Cell Mater"},{"key":"B52","doi-asserted-by":"publisher","first-page":"2515","DOI":"10.1038\/s41467-022-30247-1","article-title":"A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury","volume":"13","author":"Muruganandan","year":"2022","journal-title":"Nat. Commun."},{"key":"B53","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/978-1-0716-0989-7_2","article-title":"Expansion and chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells","volume":"2221","author":"Narcisi","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"4977","DOI":"10.1242\/dev.125.24.4977","article-title":"Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3","volume":"125","author":"Naski","year":"1998","journal-title":"Development"},{"key":"B55","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41586-019-0989-6","article-title":"A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate","volume":"567","author":"Newton","year":"2019","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1002\/jbmr.5650091107","article-title":"Analysis of type II and type X collagen synthesis in cultured growth plate chondrocytes by in situ hybridization: rapid induction of type X collagen in culture","volume":"9","author":"O'Keefe","year":"1994","journal-title":"J. Bone Min. Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1038\/ncb3067","article-title":"A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones","volume":"16","author":"Ono","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e165619","DOI":"10.1172\/jci.insight.165619","article-title":"Hedgehog activation promotes osteogenic fates of growth plate resting zone chondrocytes through transient clonal competency","volume":"9","author":"Orikasa","year":"2024","journal-title":"JCI Insight"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.5966\/sctm.2015-0256","article-title":"Generation of a bone organ by human adipose-derived stromal cells through endochondral ossification","volume":"5","author":"Osinga","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/9780470513637.ch4","article-title":"Stromal stem cells: marrow-derived osteogenic precursors","volume":"136","author":"Owen","year":"1988","journal-title":"Ciba Found. Symp."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.actbio.2016.01.037","article-title":"Differentiation of mesenchymal stem cells for cartilage tissue engineering: individual and synergetic effects of three-dimensional environment and mechanical loading","volume":"33","author":"Panadero","year":"2016","journal-title":"Acta Biomater."},{"key":"B62","doi-asserted-by":"publisher","first-page":"3254","DOI":"10.1002\/art.22136","article-title":"Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice","volume":"54","author":"Pelttari","year":"2006","journal-title":"Arthritis Rheum."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1038\/nm.3314","article-title":"Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification","volume":"19","author":"Regard","year":"2013","journal-title":"Nat. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"e79925","DOI":"10.7554\/elife.79925","article-title":"Lineage-specific differences and regulatory networks governing human chondrocyte development","volume":"12","author":"Richard","year":"2023","journal-title":"Elife"},{"key":"B65","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/371252a0","article-title":"Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia","volume":"371","author":"Rousseau","year":"1994","journal-title":"Nature"},{"key":"B66","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1359\/jbmr.041210","article-title":"Chondrocyte-specific knockout of the G protein gs\u03b1 leads to epiphyseal and Growth Plate abnormalities and ectopic chondrocyte formation","volume":"20","author":"Sakamoto","year":"2005","journal-title":"J. Bone Min. Res."},{"key":"B67","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.semcdb.2016.07.008","article-title":"Signaling pathways regulating cartilage growth plate formation and activity","volume":"62","author":"Samsa","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1083\/jcb.104.4.1077","article-title":"Localization of types I, II, and III collagen mRNAs in developing human skeletal tissues by in situ hybridization","volume":"104","author":"Sandberg","year":"1987","journal-title":"J. Cell Biol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"20417314221133480","DOI":"10.1177\/20417314221133480","article-title":"Biofabrication of the osteochondral unit and its applications: current and future directions for 3D bioprinting","volume":"13","author":"Santos-Beato","year":"2022","journal-title":"J. Tissue Eng."},{"key":"B70","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche","volume":"459","author":"Sato","year":"2009","journal-title":"Nature"},{"key":"B71","first-page":"7","article-title":"The relationship between the spleen colony-forming cell and the haemopoietic stem cell","volume":"4","author":"Schofield","year":"1978","journal-title":"Blood Cells"},{"key":"B72","doi-asserted-by":"publisher","first-page":"7251","DOI":"10.1073\/pnas.1000302107","article-title":"Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering","volume":"107","author":"Scotti","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B73","doi-asserted-by":"publisher","first-page":"dev179325","DOI":"10.1242\/dev.179325","article-title":"Skeletal stem cells: insights into maintaining and regenerating the skeleton","volume":"147","author":"Serowoky","year":"2020","journal-title":"Development"},{"key":"B74","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/0092-8674(94)90302-6","article-title":"Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia","volume":"78","author":"Shiang","year":"1994","journal-title":"Cell."},{"key":"B75","doi-asserted-by":"publisher","first-page":"034112","DOI":"10.1088\/1758-5082\/3\/3\/034112","article-title":"Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip","volume":"3","author":"Snyder","year":"2011","journal-title":"Biofabrication"},{"key":"B76","doi-asserted-by":"publisher","first-page":"3039","DOI":"10.1242\/dev.02471","article-title":"Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis","volume":"133","author":"Sp\u00e4ter","year":"2006","journal-title":"Development"},{"key":"B77","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1126\/science.161.3836.54","article-title":"Transplantation of marrow to extramedullary sites","volume":"161","author":"Tavassoli","year":"1968","journal-title":"Science"},{"key":"B78","doi-asserted-by":"publisher","first-page":"e165226","DOI":"10.1172\/jci.insight.165226","article-title":"Stimulation of skeletal stem cells in the growth plate promotes linear bone growth","volume":"9","author":"Trompet","year":"2024","journal-title":"JCI Insight"},{"key":"B79","doi-asserted-by":"publisher","first-page":"4166","DOI":"10.1038\/s41467-022-31592-x","article-title":"Periosteal stem cells control growth plate stem cells during postnatal skeletal growth","volume":"13","author":"Tsukasaki","year":"2022","journal-title":"Nat. Commun."},{"key":"B80","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1126\/science.1092436","article-title":"Defining the epithelial stem cell niche in skin","volume":"303","author":"Tumbar","year":"2004","journal-title":"Science"},{"key":"B81","doi-asserted-by":"publisher","first-page":"137","DOI":"10.22203\/ecm.v027a11","article-title":"Chondrogenically differentiated mesenchymal stromal cell pellets stimulate endochondral bone regeneration in critical-sized bone defects","volume":"27","author":"van der Stok","year":"2014","journal-title":"Eur. Cell Mater"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1016\/j.addr.2012.01.016","article-title":"Strategies for controlled delivery of growth factors and cells for bone regeneration","volume":"64","author":"Vo","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1002\/jbmr.359","article-title":"IGF-1R signaling in chondrocytes modulates growth plate development by interacting with the PTHrP\/Ihh pathway","volume":"26","author":"Wang","year":"2011","journal-title":"J. Bone Min. Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"16009","DOI":"10.1038\/boneres.2016.9","article-title":"TGF-\u03b2 and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease","volume":"4","author":"Wu","year":"2016","journal-title":"Bone Res."},{"key":"B85","doi-asserted-by":"publisher","first-page":"H178","DOI":"10.1002\/adma.201004625","article-title":"Omnidirectional printing of 3D microvascular networks","volume":"23","author":"Wu","year":"2011","journal-title":"Adv. Mater"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1026911","DOI":"10.3389\/fbioe.2022.1026911","article-title":"Superwettable and injectable GelMA-MSC microspheres promote cartilage repair in temporomandibular joints","volume":"10","author":"Yang","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.actbio.2022.05.012","article-title":"Articular cartilage reconstruction with TGF-\u03b21-simulating self-assembling peptide hydrogel-based composite scaffold","volume":"146","author":"Ye","year":"2022","journal-title":"Acta Biomater."},{"key":"B88","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s41586-023-06806-x","article-title":"A human embryonic limb cell atlas resolved in space and time","volume":"635","author":"Zhang","year":"2023","journal-title":"Nature"},{"key":"B89","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.biomaterials.2016.09.003","article-title":"Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip","volume":"110","author":"Zhang","year":"2016","journal-title":"Biomaterials"},{"key":"B90","doi-asserted-by":"publisher","first-page":"e1005214","DOI":"10.1371\/journal.pgen.1005214","article-title":"FGFR3 deficiency causes multiple chondroma-like lesions by upregulating hedgehog signaling","volume":"11","author":"Zhou","year":"2015","journal-title":"PLoS Genet."}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2025.1550713\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T02:10:25Z","timestamp":1741054225000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2025.1550713\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":90,"alternative-id":["10.3389\/fbioe.2025.1550713"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2025.1550713","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]},"article-number":"1550713"}}