{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:52:09Z","timestamp":1784548329832,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Neo Modulus (Suzhou) Medical Sci-Tech Co., Ltd.","award":["FA670F0205"],"award-info":[{"award-number":["FA670F0205"]}]},{"name":"Association for the Promotion of the Eurasia-Pacific Uninet (APE)","award":["FA670F0205"],"award-info":[{"award-number":["FA670F0205"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Over the past few years, biomaterial-based periodontal tissue engineering has gained popularity. An ideal biomaterial for treating periodontal defects is expected to stimulate periodontal-derived cells, allowing them to contribute most efficiently to tissue reconstruction. The present study focuses on evaluating the in vitro behavior of human periodontal ligament-derived stromal cells (hPDL-MSCs) when cultured on gelatin\/Polycaprolactone prototype (GPP) and volume-stable collagen matrix (VSCM). Cells were cultured onto the GPP, VSCM, or tissue culture plate (TCP) for 3, 7, and 14 days. Cell morphology, adhesion, proliferation\/viability, the gene expression of Collagen type I, alpha1 (COL1A1), Vascular endothelial growth factor A (VEGF-A), Periostin (POSTN), Cementum protein 1 (CEMP1), Cementum attachment protein (CAP), Interleukin 8 (IL-8) and Osteocalcin (OCN), and the levels of VEGF-A and IL-8 proteins were investigated. hPDL-MSCs attached to both biomaterials exhibited a different morphology compared to TCP. GPP exhibited stronger capabilities in enhancing cell viability and metabolic activity compared to VSCM. In most cases, the expression of all investigated genes, except POSTN, was stimulated by both materials, with GPP having a superior effect on COL1A1 and VEGF-A, and VSCM on OCN. The IL-8 protein production was slightly higher in cells grown on VSCM. GPP also exhibited the ability to absorb VEGF-A protein. The gene expression of POSTN was promoted by GPP and slightly suppressed by VSCM. In summary, our findings indicate that GPP electrospun nanofibers effectively promote the functional performance of PDLSCs in periodontal regeneration, particularly in the periodontal ligament and cementum compartment.<\/jats:p>","DOI":"10.3390\/ijms26020672","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T05:59:42Z","timestamp":1736920782000},"page":"672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Potential of Trilayered Gelatin\/Polycaprolactone Nanofibers for Periodontal Regeneration: An In Vitro Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7662-2945","authenticated-orcid":false,"given":"Zhiwei","family":"Tian","sequence":"first","affiliation":[{"name":"Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-8713","authenticated-orcid":false,"given":"Zhongqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Aoqi","family":"Rausch","sequence":"additional","affiliation":[{"name":"Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Clinical Division of Orthodontics, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3065-3200","authenticated-orcid":false,"given":"Christian","family":"Behm","sequence":"additional","affiliation":[{"name":"Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dino","family":"Tur","sequence":"additional","affiliation":[{"name":"Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1816-3436","authenticated-orcid":false,"given":"Hassan Ali","family":"Shokoohi-Tabrizi","sequence":"additional","affiliation":[{"name":"Core Facility Applied Physics, Laser and CAD\/CAM Technology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0485-2142","authenticated-orcid":false,"given":"Oleh","family":"Andrukhov","sequence":"additional","affiliation":[{"name":"Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Rausch-Fan","sequence":"additional","affiliation":[{"name":"Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Center for Clinical Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17038","DOI":"10.1038\/nrdp.2017.38","article-title":"Periodontal diseases","volume":"3","author":"Kinane","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1111\/jre.13337","article-title":"Burden of severe periodontitis and edentulism in 2021, with projections up to 2050: The Global Burden of Disease 2021 study","volume":"59","author":"Nascimento","year":"2024","journal-title":"J. Periodontal Res."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1600-0757.2011.00432.x","article-title":"Advanced reconstructive technologies for periodontal tissue repair","volume":"59","author":"Ramseier","year":"2012","journal-title":"Periodontol. 2000"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/j.1600-0757.2011.00438.x","article-title":"Utilizing collagen membranes for guided tissue regeneration-based root coverage","volume":"59","author":"Wang","year":"2012","journal-title":"Periodontol. 2000"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ausenda, F., Rasperini, G., Acunzo, R., Gorbunkova, A., and Pagni, G. (2019). New Perspectives in the Use of Biomaterials for Periodontal Regeneration. Materials, 12.","DOI":"10.3390\/ma12132197"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1902\/jop.2015.130685","article-title":"Periodontal regeneration\u2014Intrabony defects: A systematic review from the AAP Regeneration Workshop","volume":"86","author":"Kao","year":"2015","journal-title":"J. Periodontol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bozic, D., Catovic, I., Badovinac, A., Music, L., Par, M., and Sculean, A. (2021). Treatment of Intrabony Defects with a Combination of Hyaluronic Acid and Deproteinized Porcine Bone Mineral. Materials, 14.","DOI":"10.3390\/ma14226795"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Alauddin, M.S., Abdul Hayei, N.A., Sabarudin, M.A., and Mat Baharin, N.H. (2022). Barrier Membrane in Regenerative Therapy: A Narrative Review. Membranes, 12.","DOI":"10.3390\/membranes12050444"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Janjua, O.S., Qureshi, S.M., Shaikh, M.S., Alnazzawi, A., Rodriguez-Lozano, F.J., Pecci-Lloret, M.P., and Zafar, M.S. (2022). Autogenous Tooth Bone Grafts for Repair and Regeneration of Maxillofacial Defects: A Narrative Review. Int. J. Environ. Res. Public. Health, 19.","DOI":"10.3390\/ijerph19063690"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1177\/0885328220952250","article-title":"Biodegradable engineered fiber scaffolds fabricated by electrospinning for periodontal tissue regeneration","volume":"36","author":"Xu","year":"2021","journal-title":"J. Biomater. Appl."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dieterle, M.P., Steinberg, T., Tomakidi, P., Nohava, J., Vach, K., Schulz, S.D., Hellwig, E., and Proksch, S. (2022). Novel In Situ-Cross-Linked Electrospun Gelatin\/Hydroxyapatite Nonwoven Scaffolds Prove Suitable for Periodontal Tissue Engineering. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061286"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Swanson, W.B., Omi, M., Zhang, Z., Nam, H.K., Jung, Y., Wang, G., Ma, P.X., Hatch, N.E., and Mishina, Y. (2021). Macropore design of tissue engineering scaffolds regulates mesenchymal stem cell differentiation fate. Biomaterials, 272.","DOI":"10.1016\/j.biomaterials.2021.120769"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Imber, J.C., Roccuzzo, A., Stahli, A., Saulacic, N., Deschner, J., Sculean, A., and Bosshardt, D.D. (2021). Immunohistochemical Evaluation of Periodontal Regeneration Using a Porous Collagen Scaffold. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222010915"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Caballe-Serrano, J., Zhang, S., Ferrantino, L., Simion, M., Chappuis, V., and Bosshardt, D.D. (2019). Tissue Response to a Porous Collagen Matrix Used for Soft Tissue Augmentation. Materials, 12.","DOI":"10.3390\/ma12223721"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lin, H.H., Chao, P.G., Tai, W.C., and Chang, P.C. (2021). 3D-Printed Collagen-Based Waveform Microfibrous Scaffold for Periodontal Ligament Reconstruction. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147725"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00167-012-2292-z","article-title":"Consideration of religious sentiments while selecting a biological product for knee arthroscopy","volume":"21","author":"Goyal","year":"2013","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Zhang, H., Zhou, Y., Yu, Z., Yuan, H., Feng, B., van Rijn, P., and Zhang, Y. (2017). Alkali-Mediated Miscibility of Gelatin\/Polycaprolactone for Electrospinning Homogeneous Composite Nanofibers for Tissue Scaffolding. Macromol. Biosci., 17.","DOI":"10.1002\/mabi.201700268"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.msec.2016.10.083","article-title":"Electrospun polycaprolactone\/gelatin composites with enhanced cell-matrix interactions as blood vessel endothelial layer scaffolds","volume":"71","author":"Jiang","year":"2017","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fee, T., Surianarayanan, S., Downs, C., Zhou, Y., and Berry, J. (2016). Nanofiber Alignment Regulates NIH3T3 Cell Orientation and Cytoskeletal Gene Expression on Electrospun PCL+Gelatin Nanofibers. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154806"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1002\/jbm.b.34591","article-title":"In vitro biocompatibility of biohybrid polymers membrane evaluated in human gingival fibroblasts","volume":"108","author":"Guo","year":"2020","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1700895","DOI":"10.1002\/adhm.201700895","article-title":"Nanofibered Gelatin-Based Nonwoven Elasticity Promotes Epithelial Histogenesis","volume":"7","author":"Jedrusik","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1089\/ten.tea.2013.0594","article-title":"Nonwoven-based gelatin\/polycaprolactone membrane proves suitability in a preclinical assessment for treatment of soft tissue defects","volume":"20","author":"Schulz","year":"2014","journal-title":"Tissue Eng. Part A"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tian, Z., Zhao, Z., Rausch, M.A., Behm, C., Shokoohi-Tabrizi, H.A., Andrukhov, O., and Rausch-Fan, X. (2023). In Vitro Investigation of Gelatin\/Polycaprolactone Nanofibers in Modulating Human Gingival Mesenchymal Stromal Cells. Materials, 16.","DOI":"10.3390\/ma16247508"},{"key":"ref_25","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_26","doi-asserted-by":"crossref","unstructured":"Gil-Castell, O., Badia, J.D., Ontoria-Oviedo, I., Castellano, D., Sepulveda, P., and Ribes-Greus, A. (2020). Polycaprolactone\/gelatin-based scaffolds with tailored performance: In vitro and in vivo validation. Mater. Sci. Eng. C Mater. Biol. Appl., 107.","DOI":"10.1016\/j.msec.2019.110296"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ma, Y., Ji, Y., Huang, G., Ling, K., Zhang, X., and Xu, F. (2015). Bioprinting 3D cell-laden hydrogel microarray for screening human periodontal ligament stem cell response to extracellular matrix. Biofabrication, 7.","DOI":"10.1088\/1758-5090\/7\/4\/044105"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Liang, C., Wang, G., Liang, C., Li, M., Sun, Y., Tian, W., and Liao, L. (2023). Hierarchically patterned triple-layered gelatin-based electrospun membrane functionalized by cell-specific extracellular matrix for periodontal regeneration. Dent. Mater.","DOI":"10.1016\/j.dental.2023.10.022"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1039\/C8BM01653D","article-title":"Zein\/gelatin\/nanohydroxyapatite nanofibrous scaffolds are biocompatible and promote osteogenic differentiation of human periodontal ligament stem cells","volume":"7","author":"Ou","year":"2019","journal-title":"Biomater. Sci."},{"key":"ref_30","first-page":"1","article-title":"PERIOSTIN: Role in formation and maintenance of dental tissues","volume":"229","author":"Romanos","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.2147\/IJN.S104324","article-title":"Controlled release of recombinant human cementum protein 1 from electrospun multiphasic scaffold for cementum regeneration","volume":"11","author":"Chen","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1177\/00220345000790070901","article-title":"Cementum attachment protein enriches putative cementoblastic populations on root surfaces in vitro","volume":"79","author":"BarKana","year":"2000","journal-title":"J. Dent. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1600-0765.1990.tb00899.x","article-title":"Isolation of a fibroblast attachment protein from cementum","volume":"25","author":"McAllister","year":"1990","journal-title":"J. Periodontal Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1111\/jre.12921","article-title":"Regeneration of rat periodontium by cementum protein 1-derived peptide","volume":"56","author":"Hoz","year":"2021","journal-title":"J. Periodontal Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1002\/jbm.a.34823","article-title":"Collagen-gelatin-genipin-hydroxyapatite composite scaffolds colonized by human primary osteoblasts are suitable for bone tissue engineering applications: In vitro evidences","volume":"102","author":"Vozzi","year":"2014","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_36","first-page":"3008","article-title":"In vitro mineralization and bone osteogenesis in poly(epsilon-caprolactone)\/gelatin nanofibers","volume":"100","author":"Guarino","year":"2012","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_37","first-page":"1315","article-title":"Differences in collagen distribution of healthy and regenerated periodontium. Histomorphometric study in dogs","volume":"28","author":"Souza","year":"2013","journal-title":"Histol. Histopathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1111\/aor.14169","article-title":"Bioengineering of fibroblast-conditioned polycaprolactone\/gelatin electrospun scaffold for skin tissue engineering","volume":"46","author":"Yazdanpanah","year":"2022","journal-title":"Artif. Organs"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Huang, T.Y., Shahrousvand, M., Hsu, Y.T., and Su, W.T. (2021). Polycaprolactone\/Polyethylene Glycol Blended with Dipsacus asper Wall Extract Nanofibers Promote Osteogenic Differentiation of Periodontal Ligament Stem Cells. Polymers, 13.","DOI":"10.3390\/polym13142245"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.biomaterials.2015.02.011","article-title":"Combination of aligned PLGA\/Gelatin electrospun sheets, native dental pulp extracellular matrix and treated dentin matrix as substrates for tooth root regeneration","volume":"52","author":"Chen","year":"2015","journal-title":"Biomaterials"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Kang, M.S., Eltohamy, M., Kim, T.H., and Kim, H.W. (2016). Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149967"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/jbm.b.33480","article-title":"Bilayered construct for simultaneous regeneration of alveolar bone and periodontal ligament","volume":"104","author":"Sowmya","year":"2016","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e6932","DOI":"10.1097\/MD.0000000000006932","article-title":"Association between interleukin-8 levels and chronic periodontal disease: A PRISMA-compliant systematic review and meta-analysis","volume":"96","author":"Finoti","year":"2017","journal-title":"Medicine"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Behm, C., Nemec, M., Blufstein, A., Schubert, M., Rausch-Fan, X., Andrukhov, O., and Jonke, E. (2021). Interleukin-1beta Induced Matrix Metalloproteinase Expression in Human Periodontal Ligament-Derived Mesenchymal Stromal Cells under In Vitro Simulated Static Orthodontic Forces. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031027"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s13287-024-03759-4","article-title":"Paracrine- and cell-contact-mediated immunomodulatory effects of human periodontal ligament-derived mesenchymal stromal cells on CD4(+) T lymphocytes","volume":"15","author":"Behm","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1177\/00220345241271997","article-title":"Heterogeneity in Dental Tissue-Derived MSCs Revealed by Single-Cell RNA-seq","volume":"103","author":"Behm","year":"2024","journal-title":"J. Dent. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/672\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:28:52Z","timestamp":1759919332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26020672"],"URL":"https:\/\/doi.org\/10.3390\/ijms26020672","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]}}}