{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:38:42Z","timestamp":1790177922428,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":135,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean Government","award":["NRF-2018R1A5A2023879"],"award-info":[{"award-number":["NRF-2018R1A5A2023879"]}]},{"name":"Korean Government","award":["NRF-2022R1A2C1092088"],"award-info":[{"award-number":["NRF-2022R1A2C1092088"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean Government","award":["2022R1A2C2005011"],"award-info":[{"award-number":["2022R1A2C2005011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Treating bone defects is a critical challenge in regenerative medicine. Carbon nanomaterials, with their unique physicochemical properties, offer significant potential for enhancing bone regeneration. In this study, we developed tartaric acid (TA)-based carbon dots (CDs) by synthesizing TA with branched polyethyleneimine (bPEI). These TA-bPEI CDs were systematically evaluated to determine their effects on osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (BMSCs) and their capacity to repair calvarial defects in an in vivo model. Characterization of TA-bPEI CDs revealed a size of approximately 10\u2009nm and a positive surface charge. The CDs exhibited fluorescence emission peaks between 464 and 506\u2009nm under excitation wavelengths of 340\u2013440\u2009nm. Cytotoxicity assays demonstrated that TA-bPEI CDs maintained BMSC viability at concentrations up to 250\u2009\u03bcg\/ml. However, at concentrations of 500\u2009\u03bcg\/ml and above, apoptosis was induced. Treatment with TA-bPEI significantly enhanced osteogenic differentiation in vitro, as evidenced by increased expression of osteogenic-specific proteins such as Runx2, ALP, OCN and OPN. In vivo, the application of TA-bPEI CDs in a mouse calvarial defect model promoted robust new bone formation, reduced defect gaps, and improved bone morphometric parameters, including bone volume fraction and trabecular thickness. These results suggest that TA-bPEI CDs enhance osteogenesis by directly stimulating osteogenic differentiation and upregulating osteogenesis-specific genes. This study demonstrates the high potential of TA-bPEI CDs as a novel nanomaterial for bone regeneration applications.<\/jats:p>","DOI":"10.1093\/rb\/rbaf030","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T17:58:12Z","timestamp":1747418292000},"source":"Crossref","is-referenced-by-count":7,"title":["Tartaric acid-branched polyethyleneimine carbon dots promote repair of bone defect via osteogenic differentiation"],"prefix":"10.1093","volume":"12","author":[{"given":"Soon Chul","family":"Heo","sequence":"first","affiliation":[{"name":"Department of Oral Physiology, Periodontal Diseases Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University , Yangsan 50612,","place":["Republic of Korea"]},{"name":"Institute of Tissue Regeneration Engineering (ITREN), Mechanobiology Dental Medicine Research Center, Dankook University , Cheonan 31116,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Won","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, University of Tennessee Health Science Center , Memphis, TN 38163,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Joon","family":"Lee","sequence":"additional","affiliation":[{"name":"Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill , Chapel Hill, NC 27514,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin","family":"Garcia-Godoy","sequence":"additional","affiliation":[{"name":"Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center , Memphis, TN 38103,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Ram","family":"Keum","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, Periodontal Diseases Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University , Yangsan 50612,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Hoon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Dental Materials, School of Dentistry, Pusan National University , Yangsan 50612,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2962-9553","authenticated-orcid":false,"given":"Hyung Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, Periodontal Diseases Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University , Yangsan 50612,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"2025052300565269600_rbaf030-B1","first-page":"115","article-title":"Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis","volume":"21","author":"Manolagas","year":"2000","journal-title":"Endocr Rev"},{"key":"2025052300565269600_rbaf030-B2","doi-asserted-by":"crossref","first-page":"133202","DOI":"10.1016\/j.ijbiomac.2024.133202","article-title":"Nanosilicate-reinforced GelMA-PEGDA hydrogel promotes angiogenesis for bone regeneration","volume":"277","author":"Long","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"2025052300565269600_rbaf030-B3","doi-asserted-by":"crossref","first-page":"129927","DOI":"10.1016\/j.ijbiomac.2024.129927","article-title":"Janus silk fibroin\/polycaprolactone-based scaffold with directionally aligned fibers and porous structure for bone regeneration","volume":"262","author":"Tang","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"2025052300565269600_rbaf030-B4","doi-asserted-by":"crossref","first-page":"e2101834","DOI":"10.1002\/adhm.202101834","article-title":"Carbon-based materials for articular tissue engineering: from innovative scaffolding materials toward engineered living carbon","volume":"11","author":"Islam","year":"2022","journal-title":"Adv Healthc Mater"},{"key":"2025052300565269600_rbaf030-B5","doi-asserted-by":"crossref","first-page":"1901316","DOI":"10.1002\/advs.201901316","article-title":"Evolution and synthesis of carbon dots: from carbon dots to carbonized polymer dots","volume":"6","author":"Xia","year":"2019","journal-title":"Adv Sci (Weinh)"},{"key":"2025052300565269600_rbaf030-B6","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1021\/acscentsci.0c01306","article-title":"Carbon dots: a new type of carbon-based nanomaterial with wide applications","volume":"6","author":"Liu","year":"2020","journal-title":"ACS Cent Sci"},{"key":"2025052300565269600_rbaf030-B7","doi-asserted-by":"crossref","first-page":"19214","DOI":"10.1039\/C9NR05647E","article-title":"Carbon dots: advances in nanocarbon applications","volume":"11","author":"Kang","year":"2019","journal-title":"Nanoscale"},{"key":"2025052300565269600_rbaf030-B8","doi-asserted-by":"crossref","first-page":"100879","DOI":"10.1016\/j.nantod.2020.100879","article-title":"Hetero-atom-doped carbon dots: doping strategies, properties and applications","volume":"33","author":"Miao","year":"2020","journal-title":"Nano Today"},{"key":"2025052300565269600_rbaf030-B9","doi-asserted-by":"crossref","first-page":"6111","DOI":"10.1039\/C7CS00235A","article-title":"Carbon dots as photosensitisers for solar-driven catalysis","volume":"46","author":"Hutton","year":"2017","journal-title":"Chem Soc Rev"},{"key":"2025052300565269600_rbaf030-B10","doi-asserted-by":"crossref","first-page":"5735","DOI":"10.1038\/s41467-022-33474-8","article-title":"Near-infrared phosphorescent carbon dots for sonodynamic precision tumor therapy","volume":"13","author":"Geng","year":"2022","journal-title":"Nat Commun"},{"key":"2025052300565269600_rbaf030-B11","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1021\/acsnano.6b07138","article-title":"Accelerated bone regeneration by two-photon photoactivated carbon nitride nanosheets","volume":"11","author":"Tiwari","year":"2017","journal-title":"Acs Nano"},{"key":"2025052300565269600_rbaf030-B12","doi-asserted-by":"crossref","first-page":"50287","DOI":"10.1021\/acsami.0c15425","article-title":"Ascorbic acid-PEI carbon dots with osteogenic effects as miR-2861 carriers to effectively enhance bone regeneration","volume":"12","author":"Bu","year":"2020","journal-title":"ACS Appl Mater Interfaces"},{"key":"2025052300565269600_rbaf030-B13","doi-asserted-by":"crossref","first-page":"9115","DOI":"10.1021\/acs.langmuir.9b00595","article-title":"Carbon dots: diverse preparation, application, and perspective in surface chemistry","volume":"35","author":"Zhou","year":"2019","journal-title":"Langmuir"},{"key":"2025052300565269600_rbaf030-B14","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.3390\/nano11102525","article-title":"Carbon dots: classification, properties, synthesis, characterization, and applications in health care \u2013 an updated review (2018\u20132021)","volume":"11","author":"Mansuriya","year":"2021","journal-title":"Nanomaterials"},{"key":"2025052300565269600_rbaf030-B15","doi-asserted-by":"crossref","first-page":"e2106342","DOI":"10.1002\/smll.202106342","article-title":"Carbon dot therapeutic platforms: administration, distribution, metabolism, excretion, toxicity, and therapeutic potential","volume":"18","author":"Truskewycz","year":"2022","journal-title":"Small"},{"key":"2025052300565269600_rbaf030-B16","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jconrel.2009.07.009","article-title":"Revisit the complexation of PEI and DNA\u2014how to make low cytotoxic and highly efficient PEI gene transfection non-viral vectors with a controllable chain length and structure?","volume":"140","author":"Deng","year":"2009","journal-title":"J Control Release"},{"key":"2025052300565269600_rbaf030-B17","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.ijbiomac.2020.06.090","article-title":"Low molecular weight polyethyleneimine conjugated guar gum for targeted gene delivery to triple negative breast cancer","volume":"161","author":"Jana","year":"2020","journal-title":"Int J Biol Macromol"},{"key":"2025052300565269600_rbaf030-B18","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s11684-011-0161-7","article-title":"Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region","volume":"5","author":"Zhang","year":"2011","journal-title":"Front Med"},{"key":"2025052300565269600_rbaf030-B19","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/jcp.21200","article-title":"Adult mesenchymal stem cells for tissue engineering versus regenerative medicine","volume":"213","author":"Caplan","year":"2007","journal-title":"J Cell Physiol"},{"key":"2025052300565269600_rbaf030-B20","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1056\/NEJMra022361","article-title":"Adult stem cells for tissue repair\u2014a new therapeutic concept?","volume":"349","author":"Korbling","year":"2003","journal-title":"N Engl J Med"},{"key":"2025052300565269600_rbaf030-B21","doi-asserted-by":"crossref","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":"2025052300565269600_rbaf030-B22","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1097\/SCS.0000000000005250","article-title":"Stem cells for bone regeneration: current state and future directions","volume":"30","author":"Luby","year":"2019","journal-title":"J Craniofac Surg"},{"key":"2025052300565269600_rbaf030-B23","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.jds.2023.01.029","article-title":"Lysophosphatidic acid induces proliferation and osteogenic differentiation of human dental pulp stem cell through lysophosphatidic acid receptor 3\/extracellular signal-regulated kinase signaling axis","volume":"18","author":"Heo","year":"2023","journal-title":"J Dent Sci"},{"key":"2025052300565269600_rbaf030-B24","doi-asserted-by":"crossref","first-page":"e0116698","DOI":"10.1371\/journal.pone.0116698","article-title":"Periostin accelerates bone healing mediated by human mesenchymal stem cell-embedded hydroxyapatite\/tricalcium phosphate scaffold","volume":"10","author":"Heo","year":"2015","journal-title":"PLoS One"},{"key":"2025052300565269600_rbaf030-B25","doi-asserted-by":"crossref","first-page":"6030","DOI":"10.1021\/acs.nanolett.5b02215","article-title":"Carbon dots: a unique fluorescent cocktail of polycyclic aromatic hydrocarbons","volume":"15","author":"Fu","year":"2015","journal-title":"Nano Lett"},{"key":"2025052300565269600_rbaf030-B26","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/iwj.12231","article-title":"Basic concepts regarding fracture healing and the current options and future directions in managing bone fractures","volume":"12","author":"Bigham-Sadegh","year":"2015","journal-title":"Int Wound J"},{"key":"2025052300565269600_rbaf030-B27","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s12015-016-9665-5","article-title":"Stem cells in bone regeneration","volume":"12","author":"Walmsley","year":"2016","journal-title":"Stem Cell Rev Rep"},{"key":"2025052300565269600_rbaf030-B28","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1089\/ten.teb.2016.0454","article-title":"Osteoblast differentiation and bone matrix formation in vivo and in vitro","volume":"23","author":"Blair","year":"2017","journal-title":"Tissue Eng Part B Rev"},{"key":"2025052300565269600_rbaf030-B29","doi-asserted-by":"crossref","first-page":"269","DOI":"10.22203\/eCM.v028a19","article-title":"Role and regulation of RUNX2 in osteogenesis","volume":"28","author":"Bruderer","year":"2014","journal-title":"Eur Cell Mater"},{"key":"2025052300565269600_rbaf030-B30","doi-asserted-by":"crossref","first-page":"144855","DOI":"10.1016\/j.gene.2020.144855","article-title":"Alkaline phosphatase: structure, expression and its function in bone mineralization","volume":"754","author":"Vimalraj","year":"2020","journal-title":"Gene"},{"key":"2025052300565269600_rbaf030-B31","doi-asserted-by":"crossref","first-page":"95","DOI":"10.12659\/MSMBR.901142","article-title":"Osteoblast differentiation at a glance","volume":"22","author":"Rutkovskiy","year":"2016","journal-title":"Med Sci Monit Basic Res"},{"key":"2025052300565269600_rbaf030-B32","doi-asserted-by":"crossref","first-page":"10664","DOI":"10.1021\/ie400689q","article-title":"Use of multifunctional carboxylic acids and hydrogen peroxide to improve surface quality and minimize phosphine evolution during chemical mechanical polishing of indium phosphide surfaces","volume":"52","author":"Matovu","year":"2013","journal-title":"Ind Eng Chem Res"},{"key":"2025052300565269600_rbaf030-B33","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1021\/acsnano.6b00043","article-title":"Charge-convertible carbon dots for imaging-guided drug delivery with enhanced in vivo cancer therapeutic efficiency","volume":"10","author":"Feng","year":"2016","journal-title":"ACS Nano"},{"key":"2025052300565269600_rbaf030-B34","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.2c00542","article-title":"On the cellular uptake and exocytosis of carbon dots horizontal line significant cell type dependence and effects of cell division","author":"Liu","year":"2022","journal-title":"ACS Appl Bio Mater"},{"key":"2025052300565269600_rbaf030-B35","doi-asserted-by":"crossref","first-page":"1600271","DOI":"10.1002\/mabi.201600271","article-title":"Nano-bio engineered carbon dot-peptide functionalized water dispersible hyperbranched polyurethane for bone tissue regeneration","volume":"17","author":"Gogoi","year":"2017","journal-title":"Macromol Biosci"},{"key":"2025052300565269600_rbaf030-B36","doi-asserted-by":"crossref","first-page":"055007","DOI":"10.1088\/1748-605X\/ac812f","article-title":"Calcium and phosphorus co-doped carbon dots enhance osteogenic differentiation for calvarial defect repair in situ","volume":"17","author":"Wu","year":"2022","journal-title":"Biomed Mater"},{"key":"2025052300565269600_rbaf030-B37","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/j.actbio.2011.03.019","article-title":"Nanoscale hydroxyapatite particles for bone tissue engineering","volume":"7","author":"Zhou","year":"2011","journal-title":"Acta Biomater"},{"key":"2025052300565269600_rbaf030-B38","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1002\/jbm.b.33950","article-title":"Hydroxyapatite-polymer biocomposites for bone regeneration: a review of current trends","volume":"106","author":"Ramesh","year":"2018","journal-title":"J Biomed Mater Res B Appl Biomater"},{"key":"2025052300565269600_rbaf030-B39","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/S1525-0016(02)00053-9","article-title":"Molecular weight-dependent gene transfection activity of unmodified and galactosylated polyethyleneimine on hepatoma cells and mouse liver","volume":"7","author":"Morimoto","year":"2003","journal-title":"Mol Ther"},{"key":"2025052300565269600_rbaf030-B40","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.ymthe.2005.02.010","article-title":"A two-stage poly(ethylenimine)-mediated cytotoxicity: implications for gene transfer\/therapy","volume":"11","author":"Moghimi","year":"2005","journal-title":"Mol Ther"}],"container-title":["Regenerative Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/rb\/advance-article-pdf\/doi\/10.1093\/rb\/rbaf030\/63212593\/rbaf030.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/rb\/article-pdf\/doi\/10.1093\/rb\/rbaf030\/63212593\/rbaf030.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/rb\/article-pdf\/doi\/10.1093\/rb\/rbaf030\/63212593\/rbaf030.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T04:57:05Z","timestamp":1747976225000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/rb\/article\/doi\/10.1093\/rb\/rbaf030\/8133953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":40,"URL":"https:\/\/doi.org\/10.1093\/rb\/rbaf030","relation":{},"ISSN":["2056-3426"],"issn-type":[{"value":"2056-3426","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"rbaf030"}}