{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:50:46Z","timestamp":1793508646133,"version":"4.5.0"},"reference-count":122,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,4]],"date-time":"2019-06-04T00:00:00Z","timestamp":1559606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81704128"],"award-info":[{"award-number":["81704128"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Fundamental Research Funds for the Central Universities","award":["xjj2016099"],"award-info":[{"award-number":["xjj2016099"]}]},{"name":"University of Maryland Baltimore seed grant","award":["no number"],"award-info":[{"award-number":["no number"]}],"id":[{"id":"https:\/\/ror.org\/04rq5mt64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Maryland Dental School Bridging Fund","award":["no number"],"award-info":[{"award-number":["no number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region.<\/jats:p>","DOI":"10.3390\/cells8060537","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T09:37:58Z","timestamp":1559727478000},"page":"537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":258,"title":["Periodontal Bone-Ligament-Cementum Regeneration via Scaffolds and Stem Cells"],"prefix":"10.3390","volume":"8","author":[{"given":"Jin","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, 98 XiWu Road, Xi\u2019an 710004, China"},{"name":"Clinical Research Center of Shannxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, 98 XiWu Road, Xi\u2019an 710004, China"},{"name":"Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Ruan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, 98 XiWu Road, Xi\u2019an 710004, China"},{"name":"Clinical Research Center of Shannxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, 98 XiWu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Weir","sequence":"additional","affiliation":[{"name":"Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Neural and Pain Sciences, School of Dentistry, &amp; Program in Neuroscience, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, USA"},{"name":"Member, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Oates","sequence":"additional","affiliation":[{"name":"Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Chang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, 98 XiWu Road, Xi\u2019an 710004, China"},{"name":"Clinical Research Center of Shannxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, 98 XiWu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hockin H. K.","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA"},{"name":"Member, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Center for Stem Cell Biology &amp; Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Monjaraz, B., Santiago-Osorio, E., Monroy-Garc\u00eda, A., Ledesma-Mart\u00ednez, E., and Mendoza-N\u00fa\u00f1ez, V.M. (2018). Mesenchymal stem cells of dental origin for inducing tissue regeneration in periodontitis: A mini-review. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040944"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/jcpe.12558","article-title":"Periodontal conditions among employed adults in spain","volume":"43","author":"Carasol","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"978","DOI":"10.14219\/jada.archive.2009.0307","article-title":"Periodontitis: An archetypical biofilm disease","volume":"140","author":"Schaudinn","year":"2009","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_4","unstructured":"Han, M.A. (2018). Oral health status and behavior among cancer survivors in korea using nationwide survey. Int. J. Environ. Res. Public Health, 15."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1136\/jech-2015-206745","article-title":"Periodontitis is an independent risk indicator for atherosclerotic cardiovascular diseases among 60 174 participants in a large dental school in the netherlands","volume":"71","author":"Beukers","year":"2017","journal-title":"J. Epidemiol. Community Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1902\/jop.2013.1340019","article-title":"Periodontitis and atherosclerotic cardiovascular disease","volume":"84","author":"Tonetti","year":"2013","journal-title":"J. Periodontol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1177\/154411130401500606","article-title":"Oral health, atherosclerosis, and cardiovascular disease","volume":"15","author":"Meurman","year":"2004","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1097\/SCS.0000000000003433","article-title":"Association between odontoma and impacted teeth","volume":"28","author":"Isola","year":"2017","journal-title":"J. Craniofac. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ferlazzo, N., Curr\u00f2, M., Zinellu, A., Caccamo, D., Isola, G., Ventura, V., Carru, C., Matarese, G., and Ientile, R. (2017). Influence of mthfr genetic background on p16 and mgmt methylation in oral squamous cell cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040724"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/prd.12091","article-title":"Wound models for periodontal and bone regeneration: The role of biologic research","volume":"68","author":"Sculean","year":"2015","journal-title":"Periodontology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1601252","DOI":"10.1002\/adhm.201601251","article-title":"Tri-layered nanocomposite hydrogel scaffold for the concurrent regeneration of cementum, periodontal ligament, and alveolar bone","volume":"6","author":"Sowmya","year":"2017","journal-title":"Adv. Healthc. Mater."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4103\/srmjrds.srmjrds_17_18","article-title":"Critical issues in periodontal regeneration","volume":"9","author":"Maske","year":"2018","journal-title":"SRM J. Res. Dent. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1002\/sctm.18-0181","article-title":"Concise review: Periodontal tissue regeneration using stem cells: Strategies and translational considerations","volume":"8","author":"Xu","year":"2018","journal-title":"Stem Cells Transl. Med."},{"key":"ref_14","first-page":"59269","article-title":"Guide the tissues for periodontal regeneration (gtr): A review","volume":"9","author":"Chaudhari","year":"2017","journal-title":"Int. J. Curr. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40824-017-0095-5","article-title":"Natural graft tissues and synthetic biomaterials for periodontal and alveolar bone reconstructive applications: A review","volume":"21","author":"Sheikh","year":"2017","journal-title":"Biomater. Res."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4103\/1735-3327.150307","article-title":"Periodontal bone regeneration in intrabony defects using osteoconductive bone graft versus combination of osteoconductive and osteostimulative bone graft: A comparative study","volume":"12","author":"Anushi","year":"2015","journal-title":"Dent. Res. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1155\/2019\/1202159","article-title":"Nanocrystalline hydroxyapatite-based scaffold adsorbs and gives sustained release of osteoinductive growth factor and facilitates bone regeneration in mice ectopic model","volume":"2019","author":"Zhou","year":"2019","journal-title":"J. Nanomater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10529-019-02649-7","article-title":"Mesenchymal stem cell sheets: A new cell-based strategy for bone repair and regeneration","volume":"41","author":"Chen","year":"2019","journal-title":"Biotechnol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1177\/0022034514544301","article-title":"Multiphasic scaffolds for periodontal tissue engineering","volume":"93","author":"Ivanovski","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Park, C.H., Kim, K.H., Lee, Y.M., and Seol, Y.J. (2016). Advanced engineering strategies for periodontal complex regeneration. Materials, 9.","DOI":"10.3390\/ma9010057"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40729-017-0084-4","article-title":"Autogenous bone grafts in oral implantology\u2014Is it still a \u201cgold standard\u201d? A consecutive review of 279 patients with 456 clinical procedures","volume":"3","author":"Sakkas","year":"2017","journal-title":"Int. J. Implant Dent."},{"key":"ref_23","first-page":"55","article-title":"Regeneration of periodontal tissue: Bone replacement grafts","volume":"54","author":"Reynolds","year":"2010","journal-title":"Dent. Clin."},{"key":"ref_24","first-page":"320","article-title":"Clinical and histologic evaluation of a mineralized block allograft: Results from the developmental period (2001\u20132004)","volume":"26","author":"Keith","year":"2006","journal-title":"Int. J. Periodont. Restor. Dent."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/0142-9612(96)85915-1","article-title":"Comparison of bone regeneration with the use of mineralized and demineralized freeze-dried bone allografts: A histological and histochemical study in man","volume":"17","author":"Piattelli","year":"1996","journal-title":"Biomaterials"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.archoralbio.2016.01.004","article-title":"Maxillary sinus floor augmentation and dental implant placement using dentin matrix protein-1 gene-modified bone marrow stromal cells mixed with deproteinized boving bone: A comparative study in beagles","volume":"64","author":"Liu","year":"2016","journal-title":"Arch. Oral Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s10856-006-8471-z","article-title":"In-situ hardening hydroxyapatite-based scaffold for bone repair","volume":"17","author":"Zhang","year":"2006","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_28","first-page":"114","article-title":"Treatment of human class ii furcation defects using connective tissue grafts, bioabsorbable membrane, and resorbable hydroxylapatite: A comparative study","volume":"7","author":"Belal","year":"2005","journal-title":"J. Int. Acad. Periodontol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1002\/jbm.a.30461","article-title":"Effects of synergistic reinforcement and absorbable fiber strength on hydroxyapatite bone cement","volume":"75A","author":"Zhang","year":"2005","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1902\/jop.2006.050283","article-title":"Injectable calcium phosphate bone cement provides favorable space and a scaffold for periodontal regeneration in dogs","volume":"77","author":"Hayashi","year":"2006","journal-title":"J. Periodontol."},{"key":"ref_31","first-page":"87","article-title":"Hydroxyapatite\/pmma composites as bone cements","volume":"14","author":"Chu","year":"2004","journal-title":"BioMed. Mater. Eng."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5460","DOI":"10.1002\/adfm.201370227","article-title":"Tissue engineering: Toward strong and tough glass and ceramic scaffolds for bone repair","volume":"23","author":"Fu","year":"2013","journal-title":"Adv. Funct. Mater"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jfma.2014.10.009","article-title":"Novel microinjector for carrying bone substitutes for bone regeneration in periodontal diseases","volume":"115","author":"Tsai","year":"2016","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0736-0266(01)00140-1","article-title":"Preliminary report on the biocompatibility of a moldable, resorbable, composite bone graft consisting of calcium phosphate cement and poly (lactide-co-glycolide) microspheres","volume":"20","author":"Simon","year":"2002","journal-title":"J. Orthopaed. Res."},{"key":"ref_35","unstructured":"Brown, W.E., and Chow, L.C. (1986). Combinations of Sparingly Soluble Calcium Phosphates in Slurries and Pastes as Mineralizers and Cements. (4,612,053), U.S. Patent."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S0109-5641(03)00028-9","article-title":"Properties of elastomeric calcium phosphate cement\u2013chitosan composites","volume":"19","author":"Takagi","year":"2003","journal-title":"Dent. Mater."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17056","DOI":"10.1038\/boneres.2017.56","article-title":"Calcium phosphate cements for bone engineering and their biological properties","volume":"5","author":"Xu","year":"2017","journal-title":"Bone Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1089\/ten.teb.2009.0527","article-title":"Cell-seeding techniques in vascular tissue engineering","volume":"16","author":"Villalona","year":"2010","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.dental.2015.11.019","article-title":"A self-setting ipsmsc-alginate-calcium phosphate paste for bone tissue engineering","volume":"32","author":"Wang","year":"2016","journal-title":"Dent. Mater."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"015009","DOI":"10.1088\/1748-605X\/12\/1\/015009","article-title":"Long-term biological performance of injectable and degradable calcium phosphate cement","volume":"12","author":"Grosfeld","year":"2016","journal-title":"Biomed. Mater."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.msec.2017.02.158","article-title":"Engineering bone regeneration with novel cell-laden hydrogel microfiber-injectable calcium phosphate scaffold","volume":"75","author":"Song","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6502","DOI":"10.1016\/j.biomaterials.2010.05.017","article-title":"An injectable calcium phosphate-alginate hydrogel-umbilical cord mesenchymal stem cell paste for bone tissue engineering","volume":"31","author":"Zhao","year":"2010","journal-title":"Biomaterials"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1177\/0022034511405386","article-title":"Dental pulp stem cells, niches, and notch signaling in tooth injury","volume":"23","author":"Mitsiadis","year":"2011","journal-title":"Adv. Dent. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.actbio.2015.02.011","article-title":"Bone tissue engineering via human induced pluripotent, umbilical cord and bone marrow mesenchymal stem cells in rat cranium","volume":"18","author":"Wang","year":"2015","journal-title":"Acta Biomater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.msec.2016.08.019","article-title":"Injectable calcium phosphate with hydrogel fibers encapsulating induced pluripotent, dental pulp and bone marrow stem cells for bone repair","volume":"69","author":"Wang","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.msec.2018.04.049","article-title":"Injectable synthetic hydrogel for bone regeneration: Physicochemical characterisation of a high and a low ph gelling system","volume":"90","author":"Schweikle","year":"2018","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1097\/SCS.0000000000002932","article-title":"Is more cortical bone decortication effective on guided bone augmentation?","volume":"27","author":"Acar","year":"2016","journal-title":"J. Craniofac. Surg."},{"key":"ref_48","first-page":"2555","article-title":"Angiogenesis and bone regeneration of porous nano-hydroxyapatite\/coralline blocks coated with rhvegf165 in critical-size alveolar bone defects in vivo","volume":"10","author":"Du","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.msec.2017.05.035","article-title":"Novel hipsc-based tri-culture for pre-vascularization of calcium phosphate scaffold to enhance bone and vessel formation","volume":"79","author":"Zhang","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1021\/nn505015e","article-title":"Review of nanomaterials in dentistry: Interactions with the oral microenvironment, clinical applications, hazards, and benefits","volume":"9","author":"Besinis","year":"2015","journal-title":"ACS Nano"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Batool, F., Strub, M., Petit, C., Bugueno, I., Bornert, F., Clauss, F., Huck, O., Kuchler-Bopp, S., and Benkirane-Jessel, N. (2018). Periodontal tissues, maxillary jaw bone, and tooth regeneration approaches: From animal models analyses to clinical applications. Nanomaterials, 8.","DOI":"10.3390\/nano8050337"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.2217\/nnm.12.146","article-title":"Nanodentistry: Combining nanostructured materials and stem cells for dental tissue regeneration","volume":"7","author":"Mitsiadis","year":"2012","journal-title":"Nanomedicine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/wnan.1224","article-title":"Dental applications of nanostructured bioactive glass and its composites","volume":"5","author":"Polini","year":"2013","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Xu, H.H., Weir, M.D., Zhao, L., Moreau, J.L., Arola, D.D., and Simon, C.G. (2012). Nano-Apatitic Composite Scaffolds for Stem Cell Delivery and Bone Tissue Engineering. Emerging Nanotechnologies in Dentistry, William Andrew Publishing.","DOI":"10.1016\/B978-1-4557-7862-1.00012-2"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1177\/0022034517706678","article-title":"Nanomaterials for craniofacial and dental tissue engineering","volume":"96","author":"Li","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_56","first-page":"973","article-title":"Enhancement of bone formation by bmp-7 transduced mscs on biomimetic nano-hydroxyapatite\/polyamide composite scaffolds in repair of mandibular defects","volume":"95","author":"Li","year":"2010","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.nano.2017.08.014","article-title":"Gold nanoparticles in injectable calcium phosphate cement enhance osteogenic differentiation of human dental pulp stem cells","volume":"14","author":"Xia","year":"2018","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1186\/s12967-015-0719-2","article-title":"Pdl regeneration via cell homing in delayed replantation of avulsed teeth","volume":"13","author":"Zhu","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1600-0757.2005.00139.x","article-title":"Stem cells and periodontal regeneration","volume":"40","author":"Bartold","year":"2006","journal-title":"Periodontology 2000"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1111\/j.1582-4934.2010.01251.x","article-title":"Future dentistry: Cell therapy meets tooth and periodontal repair and regeneration","volume":"15","author":"Bostanci","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_61","first-page":"4030","article-title":"Improved biphasic calcium phosphate combined with periodontal ligament stem cells may serve as a promising method for periodontal regeneration","volume":"10","author":"Shi","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1177\/0022034513513026","article-title":"Allogeneic bone marrow mesenchymal stem cell transplantation for periodontal regeneration","volume":"93","author":"Du","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Mohammed, E., Khalil, E., and Sabry, D. (2018). Effect of adipose-derived stem cells and their exo as adjunctive therapy to nonsurgical periodontal treatment: A histologic and histomorphometric study in rats. Biomolecules, 8.","DOI":"10.3390\/biom8040167"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/jcp.22316","article-title":"Application of induced pluripotent stem (ips) cells in periodontal tissue regeneration","volume":"226","author":"Duan","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/j.1600-0757.2009.00317.x","article-title":"Does periodontal tissue regeneration really work?","volume":"51","author":"Bosshardt","year":"2009","journal-title":"Periodontol. 2000"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.sdentj.2017.11.001","article-title":"An overview of periodontal regenerative procedures for the general dental practitioner","volume":"30","author":"Siaili","year":"2018","journal-title":"Saudi Dent. J."},{"key":"ref_67","first-page":"31","article-title":"Gtr membranes: The barriers for periodontal regeneration","volume":"4","author":"Singh","year":"2013","journal-title":"DHR Int. J. Med. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.dental.2012.04.022","article-title":"Recent advances in the development of gtr\/gbr membranes for periodontal regeneration\u2014A materials perspective","volume":"28","author":"Bottino","year":"2012","journal-title":"Dent. Mater."},{"key":"ref_69","unstructured":"Cash, A. (2019). 20 Years of Guided Bone Regeneration in Implant Dentistry, Oxford University Press. [2nd ed.]."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1902\/jop.2008.070571","article-title":"Long-term results of guided tissue regeneration therapy with non-resorbable and bioabsorbable barriers. Iv. A case series of infrabony defects after 10 years","volume":"79","author":"Pretzl","year":"2008","journal-title":"J. Periodontol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1902\/jop.2011.100466","article-title":"Treatment of intrabony defects after impacted mandibular third molar removal with bioabsorbable and non-resorbable membranes","volume":"82","author":"Corinaldesi","year":"2011","journal-title":"J. Periodontol."},{"key":"ref_72","first-page":"611","article-title":"Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in rgd-modified alginate scaffold","volume":"20","author":"Moshaverinia","year":"2013","journal-title":"Tissue Eng. Part A"},{"key":"ref_73","unstructured":"Bollati, D., Morra, M., Cassinelli, C., and Cascardo, G. (2018). Implantable Devices Having Antibacterial Properties and Multifunctional Surfaces. (9,999,706), U.S. Patent."},{"key":"ref_74","first-page":"16","article-title":"Efficacy of natural biopolymer chitosan membrane for guided tissue regeneration","volume":"12","author":"Nyamsuren","year":"2018","journal-title":"Innovation"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1002\/jbm.a.34874","article-title":"In vitro and in vivo evaluation of chitosan\/\u03b2-glycerol phosphate composite membrane for guided bone regeneration","volume":"102","author":"Cui","year":"2014","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"483","DOI":"10.2147\/IJN.S184396","article-title":"Preparation and biological characterization of the mixture of poly (lactic-co-glycolic acid)\/chitosan\/ag nanoparticles for periodontal tissue engineering","volume":"14","author":"Xue","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1804730","DOI":"10.1002\/adfm.201804730","article-title":"Multiphasic collagen scaffolds for engineered tissue interfaces","volume":"28","author":"Lausch","year":"2018","journal-title":"Adv. Funct. Mater."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"055004","DOI":"10.1088\/1748-605X\/aa7b55","article-title":"Development of fish collagen\/bioactive glass\/chitosan composite nanofibers as a gtr\/gbr membrane for inducing periodontal tissue regeneration","volume":"12","author":"Zhou","year":"2017","journal-title":"Biomed. Mater."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Foster, B.L., Nagatomo, K.J., Nociti, F.H., Fong, H., Dunn, D., Tran, A.B., Wang, W., Narisawa, S., Mill\u00e1n, J.L., and Somerman, M.J. (2012). Central role of pyrophosphate in acellular cementum formation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038393"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Matalov\u00e1, E., Lungov\u00e1, V., and Sharpe, P. (2015). Development of Tooth and Associated Structures. Stem Cell Biology and Tissue Engineering in Dental Sciences, Academic Press.","DOI":"10.1016\/B978-0-12-397157-9.00030-8"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0070-2153(06)78003-6","article-title":"Advances in defining regulators of cementum development and periodontal regeneration","volume":"78","author":"Foster","year":"2007","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/prd.12062","article-title":"Cementum proteins: Role in cementogenesis, biomineralization, periodontium formation and regeneration","volume":"67","author":"Arzate","year":"2015","journal-title":"Periodontology 2000"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1042\/CBI20110168","article-title":"Cementum protein 1 (cemp1) induces differentiation by human periodontal ligament cells under three-dimensional culture conditions","volume":"36","author":"Hoz","year":"2012","journal-title":"Cell Biol. Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/(SICI)1097-0185(199606)245:2<267::AID-AR12>3.0.CO;2-N","article-title":"Cementogenesis reviewed: A comparison between human premolars and rodent molars","volume":"245","author":"Bosshardt","year":"1996","journal-title":"Anat. Rec."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1600-0722.1998.tb02198.x","article-title":"Cementum attachment protein manifestation is restricted to the mineralized tissue forming cells of the periodontium","volume":"106","author":"Savion","year":"1998","journal-title":"Eur. J. Oral Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"972313","DOI":"10.1155\/2015\/972313","article-title":"Periodontal ligament stem cells: Current status, concerns, and future prospects","volume":"2015","author":"Zhu","year":"2015","journal-title":"Stem Cells Int."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"656","DOI":"10.5966\/sctm.2016-0028","article-title":"Periodontal tissue regeneration using syngeneic adipose-derived stromal cells in a mouse model","volume":"6","author":"Lemaitre","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/j.biomaterials.2011.11.074","article-title":"Tooth root regeneration using dental follicle cell sheets in combination with a dentin matrix-based scaffold","volume":"33","author":"Yang","year":"2012","journal-title":"Biomaterials"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.archoralbio.2018.04.001","article-title":"Cementum regeneration using stem cells in the dog model: A systematic review","volume":"91","author":"Crossman","year":"2018","journal-title":"Arch. Oral Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1600-0765.2008.01106.x","article-title":"Apical tooth germ cell-conditioned medium enhances the differentiation of periodontal ligament stem cells into cementum\/periodontal ligament-like tissues","volume":"44","author":"Yang","year":"2009","journal-title":"J. Periodont. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1002\/biot.201300432","article-title":"Cell sheet engineering for regenerative medicine: Current challenges and strategies","volume":"9","author":"Owaki","year":"2014","journal-title":"Biotechnol. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1007\/s00784-018-2630-8","article-title":"Cell sheets of human dental pulp stem cells for future application in bone replacement","volume":"23","author":"Pedroni","year":"2018","journal-title":"Clin. Oral Investig."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1155\/2017\/2374161","article-title":"A concise review on the use of mesenchymal stem cells in cell sheet-based tissue engineering with special emphasis on bone tissue regeneration","volume":"2017","author":"Yorukoglu","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1016\/j.biomaterials.2009.01.032","article-title":"Periodontal regeneration with multi-layered periodontal ligament-derived cell sheets in a canine model","volume":"30","author":"Iwata","year":"2009","journal-title":"Biomaterials"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/term.1785","article-title":"Cell sheet engineering and its application for periodontal regeneration","volume":"9","author":"Iwata","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7031","DOI":"10.2147\/IJN.S90343","article-title":"Effect of micro-nano-hybrid structured hydroxyapatite bioceramics on osteogenic and cementogenic differentiation of human periodontal ligament stem cell via wnt signaling pathway","volume":"10","author":"Mao","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1177\/0022034517706070","article-title":"Leveraging stem cell homing for therapeutic regeneration","volume":"96","author":"Yin","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/nbt.2978","article-title":"Modulating the stem cell niche for tissue regeneration","volume":"32","author":"Lane","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.tibtech.2014.06.008","article-title":"Toward in situ tissue engineering: Chemokine-guided stem cell recruitment","volume":"32","author":"Andreas","year":"2014","journal-title":"Trends Biotechnol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7319","DOI":"10.1039\/C5TB01188D","article-title":"Understanding cell homing-based tissue regeneration from the perspective of materials","volume":"3","author":"Zhao","year":"2015","journal-title":"J. Mater. Chem. B"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.msec.2015.04.002","article-title":"Local administration of stromal cell-derived factor-1 promotes stem cell recruitment and bone regeneration in a rat periodontal bone defect model","volume":"53","author":"Liu","year":"2015","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1700022","DOI":"10.1002\/admt.201700022","article-title":"Advanced biotechnologies toward engineering a cell home for stem cell accommodation","volume":"2","author":"Tian","year":"2017","journal-title":"Adv. Mater. Technol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.apmt.2018.02.004","article-title":"Biomaterials for endogenous regenerative medicine: Coaxing stem cell homing and beyond","volume":"11","author":"Wu","year":"2018","journal-title":"Appl. Mater. Today"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s10439-016-1687-2","article-title":"Additive biomanufacturing: An advanced approach for periodontal tissue regeneration","volume":"45","author":"Carter","year":"2017","journal-title":"Ann. Biomed. Eng."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"143S","DOI":"10.1177\/0022034515588885","article-title":"Three-dimensional bioprinting for regenerative dentistry and craniofacial tissue engineering","volume":"94","author":"Obregon","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_106","unstructured":"Sun, J., and Lee, Y. (2018). 3d Printing of Composition-Controlled Copolymers. (15\/702,779), Google Patent."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.1016\/j.biomaterials.2012.04.038","article-title":"A biphasic scaffold design combined with cell sheet technology for simultaneous regeneration of alveolar bone\/periodontal ligament complex","volume":"33","author":"Vaquette","year":"2012","journal-title":"Biomaterials"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"5945","DOI":"10.1016\/j.biomaterials.2010.04.027","article-title":"Biomimetic hybrid scaffolds for engineering human tooth-ligament interfaces","volume":"31","author":"Park","year":"2010","journal-title":"Biomaterials"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.biomaterials.2011.09.057","article-title":"Tissue engineering bone-ligament complexes using fiber-guiding scaffolds","volume":"33","author":"Park","year":"2012","journal-title":"Biomaterials"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1089\/ten.tec.2013.0619","article-title":"Image-based, fiber guiding scaffolds: A platform for regenerating tissue interfaces","volume":"20","author":"Park","year":"2013","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/jez.b.21104","article-title":"How do genes make teeth to order through development?","volume":"306B","author":"Mitsiadis","year":"2006","journal-title":"J. Exp. Zool. Part B Mol. Dev. Evol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1002\/pi.2098","article-title":"Vapor-based polymer coatings for potential biomedical applications","volume":"55","author":"Lahann","year":"2006","journal-title":"Polym. Int."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1902\/jop.2011.100710","article-title":"Cell-and gene-based therapeutic strategies for periodontal regenerative medicine","volume":"82","author":"Rios","year":"2011","journal-title":"J. Periodontol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3550","DOI":"10.1208\/s12249-018-1161-6","article-title":"Colloidally stable small unilamellar stearyl amine lipoplexes for effective bmp-9 gene delivery to stem cells for osteogenic differentiation","volume":"19","author":"Vhora","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_115","first-page":"A452","article-title":"Gene transfer into periodontal tissue by in vivo electroporation","volume":"81","author":"Tsuchiya","year":"2002","journal-title":"J. Dent. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.ymthe.2004.01.016","article-title":"Engineering of tooth-supporting structures by delivery of pdgf gene therapy vectors","volume":"9","author":"Jin","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature02122","article-title":"A genetic basis for pseudomonas aeruginosa biofilm antibiotic resistance","volume":"426","author":"Mah","year":"2003","journal-title":"Nature"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1128\/IAI.69.5.2928-2934.2001","article-title":"Oral immunization with recombinant streptococcus gordonii expressing porphyromonas gingivalis fima domains","volume":"69","author":"Sharma","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"876316","DOI":"10.1155\/2013\/876316","article-title":"The adaptive nature of the bone-periodontal ligament-cementum complex in a ligature-induced periodontitis rat model","volume":"2013","author":"Lee","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.12659\/MSM.908791","article-title":"Mineralization induction of gingival fibroblasts and construction of a sandwich tissue-engineered complex for repairing periodontal defects","volume":"24","author":"Wu","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1089\/ten.tea.2013.0386","article-title":"Three-dimensional printed multiphase scaffolds for regeneration of periodontium complex","volume":"20","author":"Lee","year":"2014","journal-title":"Tissue Eng. Part A"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1700004","DOI":"10.1002\/adbi.201700004","article-title":"Engineering a cell home for stem cell homing and accommodation","volume":"1","author":"Wu","year":"2017","journal-title":"Adv. Biosyst."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/6\/537\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:56:04Z","timestamp":1760187364000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/6\/537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,4]]},"references-count":122,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["cells8060537"],"URL":"https:\/\/doi.org\/10.3390\/cells8060537","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,4]]}}}