{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:21:53Z","timestamp":1792790513698,"version":"4.5.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"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><jats:bold>Introduction:<\/jats:bold> Growth plate injury is a significant challenge in clinical practice, as it could severely affect the limb development of children, leading to limb deformity. Tissue engineering and 3D bioprinting technology have great potential in the repair and regeneration of injured growth plate, but there are still challenges associated with achieving successful repair outcomes.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In this study, GelMA hydrogel containing PLGA microspheres loaded with chondrogenic factor PTH(1\u201334) was combined with BMSCs and Polycaprolactone (PCL) to develop the PTH(1\u201334)@PLGA\/BMSCs\/GelMA-PCL scaffold using bio-3D printing technology.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The scaffold exhibited a three-dimensional interconnected porous network structure, good mechanical properties, biocompatibility, and was suitable for cellchondrogenic differentiation. And a rabbit model of growth plate injury was appliedto validate the effect of scaffold on the repair of injured growth plate. The resultsshowed that the scaffold was more effective than injectable hydrogel in promotingcartilage regeneration and reducing bone bridge formation. Moreover, the addition ofPCL to the scaffold provided good mechanical support, significantly reducing limbdeformities after growth plate injury compared with directly injected hydrogel.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Accordingly, our study demonstrates the feasibility of using 3D printed scaffolds for treating growth plate injuries and could offer a new strategy for the development of growth plate tissue engineering therapy.<\/jats:p>","DOI":"10.3389\/fbioe.2023.1210786","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T10:33:25Z","timestamp":1685529205000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["3D bioprinted hydrogel\/polymer scaffold with factor delivery and mechanical support for growth plate injury repair"],"prefix":"10.3389","volume":"11","author":[{"given":"Minjie","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Qiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjie","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Ben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1302\/2058-5241.5.190088","article-title":"The growth plate: A physiologic overview","volume":"5","author":"Agirdil","year":"2020","journal-title":"EFORT Open Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1002\/jbm.b.34997","article-title":"Polycaprolactone usage in additive manufacturing strategies for tissue engineering applications: A review","volume":"110","author":"Backes","year":"2022","journal-title":"J. Biomed. Mater Res. B Appl. Biomater."},{"key":"B3","doi-asserted-by":"publisher","first-page":"110496","DOI":"10.1016\/j.msec.2019.110496","article-title":"Efficient and prolonged antibacterial activity from porous plga microparticles and their application in food preservation","volume":"108","author":"Biswal","year":"2020","journal-title":"Mater Sci. Eng. C Mater Biol. Appl."},{"key":"B4","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1002\/term.192","article-title":"Signalling molecules and growth factors for tissue engineering of cartilage-what can we learn from the growth plate?","volume":"3","author":"Brochhausen","year":"2009","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1530\/JME-10-0177","article-title":"Organization of the Indian hedgehog-parathyroid hormone-related protein system in the postnatal growth plate","volume":"47","author":"Chau","year":"2011","journal-title":"J. Mol. Endocrinol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1097\/01241398-200307000-00002","article-title":"Cultured mesenchymal stem cell transfers in the treatment of partial growth arrest","volume":"23","author":"Chen","year":"2003","journal-title":"J. Pediatr. Orthop."},{"key":"B7","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1359\/JBMR.051005","article-title":"Initial characterization of pth-related protein gene-driven lacz expression in the mouse","volume":"21","author":"Chen","year":"2006","journal-title":"J. Bone Min. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"T45","DOI":"10.1530\/JME-14-0062","article-title":"Recent research on the growth plate: Mechanisms for growth plate injury repair and potential cell-based therapies for regeneration","volume":"53","author":"Chung","year":"2014","journal-title":"J. Mol. Endocrinol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1089\/biores.2014.0034","article-title":"Treating proximal tibial growth plate injuries using poly(lactic-Co-glycolic acid) scaffolds","volume":"4","author":"Clark","year":"2015","journal-title":"Biores Open Access"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1016\/j.bone.2010.02.017","article-title":"Characterization of a small animal growth plate injury model using microcomputed tomography","volume":"46","author":"Coleman","year":"2010","journal-title":"Bone"},{"key":"B11","doi-asserted-by":"publisher","first-page":"4891","DOI":"10.1039\/d1bm00535a","article-title":"3d bio-printed biphasic scaffolds with dual modification of silk fibroin for the integrated repair of osteochondral defects","volume":"9","author":"Deng","year":"2021","journal-title":"Biomater. Sci."},{"key":"B12","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":"B13","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1089\/ten.tea.2017.0091","article-title":"A tunable, three-dimensional in vitro culture model of growth plate cartilage using alginate hydrogel scaffolds","volume":"24","author":"Erickson","year":"2018","journal-title":"Tissue Eng. Part A"},{"key":"B14","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.bioactmat.2021.09.010","article-title":"Exosome-loaded extracellular matrix-mimic hydrogel with anti-inflammatory property facilitates\/promotes growth plate injury repair","volume":"10","author":"Guan","year":"2022","journal-title":"Bioact. Mater"},{"key":"B15","doi-asserted-by":"publisher","first-page":"116776","DOI":"10.1016\/j.carbpol.2020.116776","article-title":"Asc\/chondrocyte-laden alginate hydrogel\/pcl hybrid scaffold fabricated using 3d printing for auricle regeneration","volume":"248","author":"Jang","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"B16","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1159\/000095510","article-title":"Treatment of rabbit growth plate injuries with an autologous tissue-engineered composite","volume":"183","author":"Jin","year":"2006","journal-title":"Cells Tissues Organs"},{"key":"B17","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1242\/dev.105536","article-title":"A pathway to bone: Signaling molecules and transcription factors involved in chondrocyte development and maturation","volume":"142","author":"Kozhemyakina","year":"2015","journal-title":"Development"},{"key":"B18","doi-asserted-by":"publisher","first-page":"121131","DOI":"10.1016\/j.biomaterials.2021.121131","article-title":"Chitosan hydrogel\/3D-printed poly(\u03b5-caprolactone) hybrid scaffold containing synovial mesenchymal stem cells for cartilage regeneration based on tetrahedral framework nucleic acid recruitment","volume":"278","author":"Li","year":"2021","journal-title":"Biomaterials"},{"key":"B19","doi-asserted-by":"publisher","first-page":"a008334","DOI":"10.1101\/cshperspect.a008334","article-title":"Development of the endochondral skeleton","volume":"5","author":"Long","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"5099","DOI":"10.1242\/dev.128.24.5099","article-title":"Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation","volume":"128","author":"Long","year":"2001","journal-title":"Development"},{"key":"B21","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1530\/JOE-20-0045","article-title":"Home for a rest: Stem cell niche of the postnatal growth plate","volume":"246","author":"Lui","year":"2020","journal-title":"J. Endocrinol."},{"key":"B22","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":"B23","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s11914-014-0232-1","article-title":"Extracellular matrix and developing growth plate","volume":"12","author":"Myllyharju","year":"2014","journal-title":"Curr. Osteoporos. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"451","DOI":"10.2174\/1574888x1130800063","article-title":"Applications of stem cell therapy for physeal injuries","volume":"8","author":"Sanghani","year":"2013","journal-title":"Curr. Stem Cell. Res. Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1089\/ten.TEB.2017.0274","article-title":"Regenerative medicine approaches for the treatment of pediatric physeal injuries","volume":"24","author":"Shaw","year":"2018","journal-title":"Tissue Eng. Part B Rev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1007\/s12033-018-0084-5","article-title":"Pcl-based composite scaffold matrices for tissue engineering applications","volume":"60","author":"Siddiqui","year":"2018","journal-title":"Mol. Biotechnol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3087","DOI":"10.3390\/ma13143087","article-title":"Potential implantable nanofibrous biomaterials combined with stem cells for subchondral bone regeneration","volume":"13","author":"Smaida","year":"2020","journal-title":"Mater. (Basel)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"E202","DOI":"10.1002\/term.1670","article-title":"Treatment of growth plate injury using igf-I-loaded plga scaffolds","volume":"9","author":"Sundararaj","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e2200471","DOI":"10.1002\/adhm.202200471","article-title":"Growing pains: The need for engineered platforms to study growth plate biology","volume":"11","author":"Tiffany","year":"2022","journal-title":"Adv. Healthc. Mater"},{"key":"B30","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1080\/000164702320155383","article-title":"Treatment of growth plate injury with autogenous chondrocytes: A study in rabbits","volume":"73","author":"Tobita","year":"2002","journal-title":"Acta Orthop. Scand."},{"key":"B31","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jconrel.2017.01.045","article-title":"Cmrna\/lipoplex encapsulation in plga microspheres enables transfection via calcium phosphate cement (Cpc)\/Plga composites","volume":"249","author":"Utzinger","year":"2017","journal-title":"J. Control Release"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1016\/j.jbiomech.2009.05.021","article-title":"Growth Plate mechanics and mechanobiology. A survey of present understanding","volume":"42","author":"Villemure","year":"2009","journal-title":"J. Biomech."},{"key":"B33","doi-asserted-by":"publisher","first-page":"654087","DOI":"10.3389\/fbioe.2021.654087","article-title":"Enlightenment of growth plate regeneration based on cartilage repair theory: A review","volume":"9","author":"Wang","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"213","DOI":"10.2174\/157488806776956904","article-title":"Repair of injured articular and growth plate cartilage using mesenchymal stem cells and chondrogenic gene therapy","volume":"1","author":"Xian","year":"2006","journal-title":"Curr. Stem Cell. Res. Ther."},{"key":"B35","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/s41536-022-00256-1","article-title":"A 3d printed mimetic composite for the treatment of growth plate injuries in a rabbit model","volume":"7","author":"Yu","year":"2022","journal-title":"NPJ Regen. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.biomaterials.2015.08.045","article-title":"Synthesis, properties, and biomedical applications of gelatin methacryloyl (gelma) hydrogels","volume":"73","author":"Yue","year":"2015","journal-title":"Biomaterials"}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2023.1210786\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T10:33:27Z","timestamp":1685529207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2023.1210786\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,31]]},"references-count":36,"alternative-id":["10.3389\/fbioe.2023.1210786"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2023.1210786","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,31]]},"article-number":"1210786"}}