{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T18:52:29Z","timestamp":1792867949124,"version":"4.5.0"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,3,28]],"date-time":"2018-03-28T00:00:00Z","timestamp":1522195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Periodontal disease is a widespread disease, which without proper treatment, may lead to tooth loss in adults. Because stem cells from the inflammatory microenvironment created by periodontal disease exhibit impaired regeneration potential even under favorable conditions, it is difficult to obtain satisfactory therapeutic outcomes using traditional treatments, which only focus on the control of inflammation. Therefore, a new stem cell-based therapy known as cell aggregates\/cell sheets technology has emerged. This approach provides sufficient numbers of stem cells with high viability for treating the defective site and offers new hope in the field of periodontal regeneration. However, it is not sufficient for regenerating periodontal tissues by delivering cell aggregates\/cell sheets to the impaired microenvironment in order to suppress the function of resident cells. In the present review, we summarize some promising bioactive molecules that act as cellular signals, which recreate a favorable microenvironment for tissue regeneration, recruit endogenous cells into the defective site and enhance the viability of exogenous cells.<\/jats:p>","DOI":"10.3390\/ijms19041016","type":"journal-article","created":{"date-parts":[[2018,3,29]],"date-time":"2018-03-29T05:26:37Z","timestamp":1522301197000},"page":"1016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Contributions of Bioactive Molecules in Stem Cell-Based Periodontal Regeneration"],"prefix":"10.3390","volume":"19","author":[{"given":"An-Qi","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hu","family":"Hu","sequence":"additional","affiliation":[{"name":"Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Jin","sequence":"additional","affiliation":[{"name":"Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Shu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Xuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1902\/annals.1999.4.1.1","article-title":"Development of a classification system for periodontal diseases and conditions","volume":"4","author":"Armitage","year":"1999","journal-title":"Ann. Periodontol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0140-6736(05)67728-8","article-title":"Periodontal diseases","volume":"366","author":"Pihlstrom","year":"2005","journal-title":"Lancet"},{"key":"ref_3","first-page":"1383","article-title":"Periodontal diseases and systemic diseases","volume":"27","author":"Amano","year":"2017","journal-title":"Clin. Calcium"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1128\/JB.183.12.3770-3783.2001","article-title":"Bacterial diversity in human subgingival plaque","volume":"183","author":"Paster","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4103\/0972-0707.92599","article-title":"Biologic width and its importance in periodontal and restorative dentistry","volume":"15","author":"Nugala","year":"2012","journal-title":"J. Conserv. Dent."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6320","DOI":"10.1016\/j.biomaterials.2012.05.048","article-title":"Stem cell-delivery therapeutics for periodontal tissue regeneration","volume":"33","author":"Chen","year":"2012","journal-title":"Biomaterials"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1182\/blood.V91.3.756","article-title":"Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases","volume":"91","author":"Slavin","year":"1998","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rohban, R., and Pieber, T.R. (2017). Mesenchymal Stem and Progenitor Cells in Regeneration, Tissue Specificity and Regenerative Potential. Stem Cells Int., 2017.","DOI":"10.1155\/2017\/5173732"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0140-6736(04)16627-0","article-title":"Investigation of multipotent postnatal stem cells from human periodontal ligament","volume":"364","author":"Seo","year":"2004","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5521","DOI":"10.1016\/j.actbio.2012.10.041","article-title":"High-resolution PLA-based composite scaffolds via 3-D printing technology","volume":"9","author":"Serra","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_11","doi-asserted-by":"crossref","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":"ref_12","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.1002\/adma.201400154","article-title":"Phage nanofibers induce vascularized osteogenesis in 3D printed bone scaffolds","volume":"26","author":"Wang","year":"2014","journal-title":"Adv. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1016\/j.biomaterials.2012.11.012","article-title":"The guidance of stem cell differentiation by substrate alignment and mechanical stimulation","volume":"34","author":"Subramony","year":"2013","journal-title":"Biomaterials"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hu, X., Wang, Y., Tan, Y., Wang, J., Liu, H., Wang, Y., Yang, S., Shi, M., Zhao, S., and Zhang, Y. (2017). A Difunctional Regeneration Scaffold for Knee Repair based on Aptamer-Directed Cell Recruitment. Adv. Mater., 29.","DOI":"10.1002\/adma.201605235"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/scitranslmed.aal3128","article-title":"In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs","volume":"9","author":"Bez","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1525-1594.2009.00991.x","article-title":"A Novel Possible Strategy Based on Self-Assembly Approach to Achieve Complete Periodontal Regeneration","volume":"34","author":"Yang","year":"2010","journal-title":"Artif. Organs"},{"key":"ref_17","first-page":"1","article-title":"Osthole improves function of periodontitis periodontal ligament stem cells via epigenetic modification in cell sheets engineering","volume":"7","author":"Sun","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/jre.12485","article-title":"Platelet-rich fibrin\/aspirin complex promotes alveolar bone regeneration in periodontal defect in rats","volume":"53","author":"Du","year":"2018","journal-title":"J. Periodontal Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.freeradbiomed.2012.11.002","article-title":"Immune modulatory and antioxidant effects of melatonin in experimental periodontitis in rats","volume":"55","author":"Kara","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.actbio.2015.10.031","article-title":"Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis","volume":"29","author":"Bhattarai","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/jcpe.12501","article-title":"Stem cells derived from \u201cinflamed\u201d and healthy periodontal ligament tissues and their sheet functionalities, a patient-matched comparison","volume":"43","author":"Tang","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref_22","unstructured":"Sui, B.D., Hu, C.H., Liu, A.Q., Zheng, C.X., Xuan, K., and Jin, Y. (2017). Stem cell-based bone regeneration in diseased microenvironments, Challenges and solutions. Biomaterials."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1111\/jcpe.12009","article-title":"Mesenchymal stem cells derived from inflamed periodontal ligaments exhibit impaired immunomodulation","volume":"39","author":"Liu","year":"2012","journal-title":"J. Clin. Periodontol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Liu, J., Wang, L., Liu, W., Li, Q., Jin, Z., and Jin, Y. (2014). Dental follicle cells rescue the regenerative capacity of periodontal ligament stem cells in an inflammatory microenvironment. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108752"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1089\/ten.tea.2008.0562","article-title":"Loss of proliferation and differentiation capacity of aged human periodontal ligament stem cells and rejuvenation by exposure to the young extrinsic environment","volume":"15","author":"Zheng","year":"2009","journal-title":"Tissue Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/boc.201200064","article-title":"Inflammatory environment induces gingival tissue-specific mesenchymal stem cells to differentiate towards a pro-fibrotic phenotype","volume":"105","author":"Li","year":"2013","journal-title":"Biol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.progpolymsci.2015.02.004","article-title":"Advancing biomaterials of human origin for tissue engineering","volume":"53","author":"Chen","year":"2016","journal-title":"Prog. Polym. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1089\/scd.2016.0349","article-title":"Effect of the Microenvironment on Mesenchymal Stem Cell Paracrine Signaling, Opportunities to Engineer the Therapeutic Effect","volume":"26","author":"Kusuma","year":"2017","journal-title":"Stem Cells Dev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/stem.2575","article-title":"Concise Review, MSC-Derived Exosomes for Cell-Free Therapy","volume":"35","author":"Phinney","year":"2017","journal-title":"Stem Cells"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.yexcr.2016.10.008","article-title":"Conditioned medium of periodontal ligament mesenchymal stem cells exert anti-inflammatory effects in lipopolysaccharide-activated mouse motoneurons","volume":"349","author":"Rajan","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ohyashiki, J.H., Umezu, T., and Ohyashiki, K. (2018). Extracellular vesicle-mediated cell-cell communication in haematological neoplasms. Philos. Trans. R. Soc. Lond. B Biol. Sci., 373.","DOI":"10.1098\/rstb.2016.0484"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1111\/jre.12405","article-title":"In vivo periodontal tissue regeneration by periodontal ligament stem cells and endothelial cells in three-dimensional cell sheet constructs","volume":"52","author":"Panduwawala","year":"2017","journal-title":"J. Periodontal Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13287-016-0288-1","article-title":"Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: A randomized clinical trial","volume":"7","author":"Chen","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1902\/jop.2015.150389","article-title":"Effect of Enamel Matrix Derivative Liquid on Osteoblast and Periodontal Ligament Cell Proliferation and Differentiation","volume":"87","author":"Miron","year":"2016","journal-title":"J. Periodontol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/clr.12802","article-title":"Osteogain improves osteoblast adhesion, proliferation and differentiation on a bovine-derived natural bone mineral","volume":"28","author":"Miron","year":"2017","journal-title":"Clin. Oral Implants Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/jcpe.12546","article-title":"Twenty years of enamel matrix derivative, the past, the present and the future","volume":"43","author":"Miron","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/jbm.a.36227","article-title":"Extracellular matrix derived from periodontal ligament cells maintains their stemness and enhances redifferentiation via the wnt pathway","volume":"106","author":"Zhang","year":"2017","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/jcpe.12663","article-title":"Effects of EMD liquid (Osteogain) on periodontal healing in class III furcation defects in monkeys","volume":"44","author":"Shirakata","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_39","first-page":"86","article-title":"Efficacy of platelet-rich fibrin vs. enamel matrix derivative in the treatment of periodontal intrabony defects, a clinical and cone beam computed tomography study","volume":"16","author":"Gupta","year":"2014","journal-title":"J. Int. Acad. Periodontol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"797","DOI":"10.11607\/prd.2842","article-title":"Enamel Matrix Derivative Proteins in Combination with a Flapless Approach for Periodontal Regeneration of Intrabony Defects, A 2-Year Prospective Case Series","volume":"36","author":"Aimetti","year":"2016","journal-title":"Int. J. Periodontics Restor. Dent."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9990","DOI":"10.1016\/j.biomaterials.2013.09.030","article-title":"Dual delivery of PDGF and simvastatin to accelerate periodontal regeneration in vivo","volume":"34","author":"Chang","year":"2013","journal-title":"Biomaterials"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/gt.2016.73","article-title":"Effect of sustained PDGF nonviral gene delivery on repair of tooth-supporting bone defects","volume":"24","author":"Plonka","year":"2016","journal-title":"Gene Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1517\/14712598.2011.554814","article-title":"Platelet-derived growth factor applications in periodontal and peri-implant bone regeneration","volume":"11","author":"Kaigler","year":"2011","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/jcpe.12643","article-title":"Regenerative potential of leucocyte- and platelet-rich fibrin. Part, A.; intra-bony defects, furcation defects and periodontal plastic surgery. A systematic review and meta-analysis","volume":"44","author":"Castro","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1111\/jcpe.12598","article-title":"Evaluation of the adjunctive effect of platelet-rich fibrin to enamel matrix derivative in the treatment of intrabony defects. Six-month results of a randomized, split-mouth, controlled clinical study","volume":"43","author":"Demirer","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/6205910","article-title":"Phase I\/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three-Dimensional Woven-Fabric Scaffold for Periodontitis","volume":"2016","author":"Baba","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9937","DOI":"10.1016\/j.biomaterials.2013.09.017","article-title":"The effect of the coumarin-like derivative osthole on the osteogenic properties of human periodontal ligament and jaw bone marrow mesenchymal stem cell sheets","volume":"34","author":"Gao","year":"2013","journal-title":"Biomaterials"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.freeradbiomed.2014.07.034","article-title":"Resveratrol improves oxidative stress and prevents the progression of periodontitis via the activation of the Sirt1\/AMPK and the Nrf2\/antioxidant defense pathways in a rat periodontitis model","volume":"75","author":"Tamaki","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","first-page":"1","article-title":"Quercitrin for periodontal regeneration, effects on human gingival fibroblasts and mesenchymal stem cells","volume":"5","author":"Monjo","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1902\/jop.2014.130438","article-title":"Identification of quercitrin as a potential therapeutic agent for periodontal applications","volume":"85","author":"Monjo","year":"2014","journal-title":"J. Periodontol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E3893","DOI":"10.1073\/pnas.1501759112","article-title":"PDGFB-based stem cell gene therapy increases bone strength in the mouse","volume":"112","author":"Chen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wang, Z., Feng, Z., Wu, G., Bai, S., Dong, Y., Chen, F., and Zhao, Y. (2016). The use of platelet-rich fibrin combined with periodontal ligament and jaw bone mesenchymal stem cell sheets for periodontal tissue engineering. Sci. Rep., 6.","DOI":"10.1038\/srep28126"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"55016","DOI":"10.1088\/1748-6041\/10\/5\/055016","article-title":"Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges","volume":"10","author":"Nakajima","year":"2015","journal-title":"Biomed. Mater."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Jahanban-Esfahlan, R., Mehrzadi, S., Reiter, R.J., Seidi, K., Majidinia, M., Baghi, H.B., Khatami, N., Yousefi, B., and Sadeghpour, A. (2017). Melatonin in regulation of inflammatory pathways in rheumatoid arthritis and osteoarthritis, involvement of circadian clock genes. Br. J. Pharmacol.","DOI":"10.1111\/bph.13898"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.7150\/thno.15412","article-title":"Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion","volume":"6","author":"Shuai","year":"2016","journal-title":"Theranostics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.phrs.2017.09.003","article-title":"Melatonin and periodontal tissues, Molecular and clinical perspectives","volume":"125","author":"Carpentieri","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8835","DOI":"10.1016\/j.biomaterials.2013.07.093","article-title":"Design of a multiple drug delivery system directed at periodontitis","volume":"34","author":"Sundararaj","year":"2013","journal-title":"Biomaterials"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s10096-015-2323-z","article-title":"Biofilm-specific antibiotic tolerance and resistance","volume":"34","author":"Olsen","year":"2015","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_59","first-page":"1","article-title":"Osthole, A Review on Its Bioactivities, Pharmacological Properties, and Potential as Alternative Medicine","volume":"2015","author":"Zhang","year":"2015","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s00223-016-0189-4","article-title":"Osthole Promotes Endochondral Ossification and Accelerates Fracture Healing in Mice","volume":"99","author":"Zhang","year":"2016","journal-title":"Calcif. Tissue Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1002\/jbmr.460","article-title":"Resveratrol promotes osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1\/FOXO3A axis","volume":"26","author":"Tseng","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1517\/17425247.2014.919253","article-title":"Resveratrol, review on therapeutic potential and recent advances in drug delivery","volume":"11","author":"Pangeni","year":"2014","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/eji.200425778","article-title":"In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway","volume":"35","author":"Comalada","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.biopha.2017.02.073","article-title":"Quercitrin attenuates osteoporosis in ovariectomized rats by regulating mitogen-activated protein kinase (MAPK) signaling pathways","volume":"89","author":"Xing","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6415","DOI":"10.1016\/j.biomaterials.2005.04.061","article-title":"Cell sheet engineering, recreating tissues without biodegradable scaffolds","volume":"26","author":"Yang","year":"2005","journal-title":"Biomaterials"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.addr.2007.03.019","article-title":"Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering","volume":"59","author":"Moioli","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1016\/j.bbagen.2014.01.010","article-title":"Extracellular matrix: A dynamic microenvironment for stem cell niche","volume":"1840","author":"Gattazzo","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/(SICI)1097-4636(19990615)45:4<355::AID-JBM10>3.0.CO;2-7","article-title":"Decrease in culture temperature releases monolayer endothelial cell sheets together with deposited fibronectin matrix from temperature-responsive culture surfaces","volume":"45","author":"Kushida","year":"1999","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00441-010-1009-1","article-title":"Assessment of cell sheets derived from human periodontal ligament cells, a pre-clinical study","volume":"341","author":"Washio","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1089\/ten.tec.2008.0561","article-title":"Tissue engineering of cementum\/periodontal-ligament complex using a novel three-dimensional pellet cultivation system for human periodontal ligament stem cells","volume":"15","author":"Yang","year":"2009","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s13287-016-0417-x","article-title":"Composite cell sheet for periodontal regeneration, crosstalk between different types of MSCs in cell sheet facilitates complex periodontal-like tissue regeneration","volume":"7","author":"Zhang","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1016\/j.biomaterials.2013.12.061","article-title":"The effect of licochalcone A on cell-aggregates ECM secretion and osteogenic differentiation during bone formation in metaphyseal defects in ovariectomized rats","volume":"35","author":"Shang","year":"2014","journal-title":"Biomaterials"},{"key":"ref_73","first-page":"1","article-title":"Licochalcone A up-regulates of FasL in mesenchymal stem cells to strengthen bone formation and increase bone mass","volume":"4","author":"Ming","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/term.1953","article-title":"Combination of platelet-rich plasma within periodontal ligament stem cell sheets enhances cell differentiation and matrix production","volume":"11","author":"Xu","year":"2017","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1111\/acel.12635","article-title":"Anti-aging pharmacology in cutaneous wound healing effects of metformin, resveratrol, and rapamycin by local application","volume":"16","author":"Zhao","year":"2017","journal-title":"Aging Cell"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/4\/1016\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:58:51Z","timestamp":1760194731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/4\/1016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,28]]},"references-count":75,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4]]}},"alternative-id":["ijms19041016"],"URL":"https:\/\/doi.org\/10.3390\/ijms19041016","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,28]]}}}