{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:39:03Z","timestamp":1792654743368,"version":"4.5.0"},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE031476"],"award-info":[{"award-number":["R01DE031476"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Combined endodontic\u2010periodontal diseases require integrated endodontic and periodontal treatment. However, extensive bone loss can limit the use of conventional approaches, necessitating regenerative methods such as guided tissue regeneration to manage intrabony defects. Yerba mate (YM,\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Ilex paraguariensis<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) exhibits antioxidant and anti\u2010inflammatory properties and has been shown to reduce osteoclastogenesis and inflammation\u2010associated bone loss, supporting its potential as a bioactive compound for incorporation into guided tissue regeneration biomaterials. This study aimed to develop and characterize polycaprolactone (PCL)\/gelatin (Gel) scaffolds containing YM via electrospinning to support mineralized tissue formation and control inflammation. Electrospun PCL\/Gel scaffolds, with and without YM, were obtained using optimized parameters and then chemically crosslinked. Fiber morphology and composition were assessed by scanning electron microscopy (SEM) and Fourier\u2010transform infrared spectroscopy (FTIR), and swelling, degradation, and mechanical properties were evaluated. Biological characterization used periodontal ligament stem cells (PDLSCs) cultured on the scaffolds to assess metabolic activity, adhesion\/spreading, and mineralized matrix deposition. The immunomodulatory effect of scaffold extracts was evaluated in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                    <\/jats:styled-content>\n                    LPS\u2010challenged macrophages (RAW 264.7) by measuring TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b1. Biocompatibility and collagen deposition were further assessed in\u00a0vivo in the subcutaneous tissue of rats at 7 and 28\u2009days. Data were analyzed using appropriate tests (\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2009=\u20095%). Bead\u2010free fibers formed regardless of YM incorporation, and YM increased fiber diameter after crosslinking (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Young's modulus and elongation at break were unchanged, although YM reduced tensile strength (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0107). YM incorporation was non\u2010cytotoxic and did not impair mineralization, while reducing IL\u20106 and TNF\u2010\u03b1 without affecting IL\u20101\u03b1. In\u00a0vivo, YM\u2010loaded scaffolds significantly reduced the inflammatory infiltrate at both time points without altering collagen deposition. These findings demonstrate that YM can be electrospun with PCL\/Gel to produce cytocompatible, anti\u2010inflammatory membranes with potential for endo\u2010perio lesion management.\n                  <\/jats:p>","DOI":"10.1002\/jbm.a.70177","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:55:52Z","timestamp":1792652152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti\u2010Inflammatory Yerba Mate\u2010Loaded Electrospun Polycaprolactone\/Gelatin Membranes for the Management of Endodontic\u2010Periodontal Lesions"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3189-1542","authenticated-orcid":false,"given":"Caroline","family":"Anselmi","sequence":"first","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics School of Dentistry, University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0105-8494","authenticated-orcid":false,"given":"Sahar","family":"Aminmansour","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics School of Dentistry, University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-5040","authenticated-orcid":false,"given":"Igor P.","family":"Mendes Soares","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics School of Dentistry, University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Dental Materials and Prosthodontics S\u00e3o Paulo State University (UNESP), School of Dentistry  Araraquara Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Aminmansour","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics School of Dentistry, University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9886-8590","authenticated-orcid":false,"given":"Lais M.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics School of Dentistry, University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Dental Materials and Prosthodontics S\u00e3o Paulo State University (UNESP), School of Dentistry  Araraquara Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3629-4904","authenticated-orcid":false,"given":"Carolina Sayuri","family":"Wajima","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics School of Dentistry, University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Restorative Dentistry S\u00e3o Paulo State University (UNESP), School of Dentistry  Ara\u00e7atuba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6032-6922","authenticated-orcid":false,"given":"Sarah","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics School of Dentistry, University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2348-7846","authenticated-orcid":false,"given":"Luciano T. A.","family":"Cintra","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry S\u00e3o Paulo State University (UNESP), School of Dentistry  Ara\u00e7atuba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4125-8441","authenticated-orcid":false,"given":"Renan","family":"Dal\u2010Fabbro","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics School of Dentistry, University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8740-2464","authenticated-orcid":false,"given":"Marco C.","family":"Bottino","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics School of Dentistry, University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Biomedical Engineering College of Engineering, University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"issue":"12","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1016\/j.joen.2015.08.022","article-title":"Microbiomes of Endodontic\u2010Periodontal Lesions Before and After Chemomechanical Preparation","volume":"41","author":"Gomes B. P.","year":"2015","journal-title":"Journal of Endodontics"},{"issue":"1","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nri3785","article-title":"Periodontitis: From Microbial Immune Subversion to Systemic Inflammation","volume":"15","author":"Hajishengallis G.","year":"2015","journal-title":"Nature Reviews. Immunology"},{"issue":"1","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jdent.2008.09.009","article-title":"Antimicrobial Action of Intracanal Medicaments on the External Root Surface","volume":"37","author":"Gomes B. P.","year":"2009","journal-title":"Journal of Dentistry"},{"issue":"4","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1902\/jop.1972.43.4.202","article-title":"The Relationship of Endodontic\u2010Periodontic Lesions","volume":"43","author":"Simon J. H.","year":"1972","journal-title":"Journal of Periodontology"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"e942544","DOI":"10.12659\/MSM.942544","article-title":"Endo\u2010Perio Lesions and Dentists' Treatment Approach: A Survey","volume":"30","author":"Durmazpinar P. M.","year":"2024","journal-title":"Medical Science Monitor"},{"issue":"2","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1600-051X.1998.tb02419.x","article-title":"Microbial Complexes in Subgingival Plaque","volume":"25","author":"Socransky S. S.","year":"1998","journal-title":"Journal of Clinical Periodontology"},{"issue":"1","key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"e117","DOI":"10.4317\/medoral.23231","article-title":"Comparison of GTR, T\u2010PRF and Open\u2010Flap Debridement in the Treatment of Intrabony Defects With Endo\u2010Perio Lesions: A Randomized Controlled Trial","volume":"25","author":"Ustaoglu G.","year":"2020","journal-title":"Medicina Oral, Patolog\u00eda Oral y Cirug\u00eda Bucal"},{"issue":"5","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/j.1365-2842.2009.01939.x","article-title":"Tissue Engineering: State of the Art in Oral Rehabilitation","volume":"36","author":"Scheller E. L.","year":"2009","journal-title":"Journal of Oral Rehabilitation"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.desal.2014.09.033","article-title":"A Review on Electrospinning for Membrane Fabrication: Challenges and Applications","volume":"356","author":"Ahmed F. 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Y.","year":"2024","journal-title":"J Funct Biomater"},{"issue":"9","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1021\/mp3001952","article-title":"Polymeric Modification and Its Implication in Drug Delivery: Poly\u2010Epsilon\u2010Caprolactone (PCL) as a Model Polymer","volume":"9","author":"Dash T. K.","year":"2012","journal-title":"Molecular Pharmaceutics"},{"issue":"1","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/jbm.a.30528","article-title":"Poly\u2010Epsilon\u2010Caprolactone\/Hydroxyapatite Composites for Bone Regeneration: In\u00a0Vitro Characterization and Human Osteoblast Response","volume":"76","author":"Causa F.","year":"2006","journal-title":"Journal of Biomedical Materials Research. 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C, Materials for Biological Applications"},{"issue":"3","key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.biomaterials.2012.10.026","article-title":"Tissue Engineered Plant Extracts as Nanofibrous Wound Dressing","volume":"34","author":"Jin G.","year":"2013","journal-title":"Biomaterials"},{"issue":"2","key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s10856-013-5077-0","article-title":"Media\u2010Based Effects on the Hydrolytic Degradation and Crystallization of Electrospun Synthetic\u2010Biologic Blends","volume":"25","author":"Nelson M. T.","year":"2014","journal-title":"Journal of Materials Science. Materials in Medicine"},{"issue":"1","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.biomaterials.2013.09.082","article-title":"The Influence of Gelatin\/PCL Ratio and 3\u2010D Construct Shape of Electrospun Membranes on Cartilage Regeneration","volume":"35","author":"Zheng R.","year":"2014","journal-title":"Biomaterials"},{"issue":"1","key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jobcr.2019.10.003","article-title":"Polycaprolactone as Biomaterial for Bone Scaffolds: Review of Literature","volume":"10","author":"Dwivedi R.","year":"2020","journal-title":"Journal of Oral Biology and Craniofacial Research"},{"issue":"10","key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.progpolymsci.2010.04.002","article-title":"The Return of a Forgotten Polymer\u2014Polycaprolactone in the 21st Century","volume":"35","author":"Woodruff M. A.","year":"2010","journal-title":"Progress in Polymer Science"},{"issue":"4","key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3390\/jfb15040097","article-title":"Functionalization of PCL\u2010Based Fiber Scaffolds With Different Sources of Calcium and Phosphate and Odontogenic Potential on Human Dental Pulp Cells","volume":"15","author":"Anselmi C.","year":"2024","journal-title":"J Funct Biomater"},{"issue":"9","key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3390\/jfb14090481","article-title":"Electrospun Scaffolds as Antimicrobial Herbal Extract Delivery Vehicles for Wound Healing","volume":"14","author":"Ersanli C.","year":"2023","journal-title":"J Funct Biomater"},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"100015","DOI":"10.1016\/j.bea.2021.100015","article-title":"Engineered Herbal Scaffolds for Tissue Repair and Regeneration: Recent Trends and Technologies","volume":"2","author":"Agarwal T.","year":"2021","journal-title":"Biomedical Engineering Advances"},{"issue":"1","key":"e_1_2_10_27_1","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1080\/87559129.2021.1885436","article-title":"Natural Hydrogels, the Interesting Carriers for Herbal Extracts","volume":"38","author":"Fathi M.","year":"2022","journal-title":"Food Reviews International"},{"issue":"13","key":"e_1_2_10_28_1","doi-asserted-by":"crossref","first-page":"11309","DOI":"10.1021\/acsami.6b16120","article-title":"Hydrogel\u2010Based Materials for Delivery of Herbal Medicines","volume":"9","author":"Lai W. F.","year":"2017","journal-title":"ACS Applied Materials & Interfaces"},{"issue":"3","key":"e_1_2_10_29_1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jtcme.2020.07.002","article-title":"Adipose Tissue of Female Wistar Rats Respond to \n                     Ilex paraguariensis\n                   Treatment After Ovariectomy Surgery","volume":"11","author":"Rocha D. S.","year":"2021","journal-title":"Journal of Traditional and Complementary Medicine"},{"issue":"11","key":"e_1_2_10_30_1","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.3390\/nu10111682","article-title":"Health Benefits of Bioactive Compounds From the Genus Ilex, a Source of Traditional Caffeinated Beverages","volume":"10","author":"Gan R. Y.","year":"2018","journal-title":"Nutrients"},{"issue":"1","key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/iej.70031","article-title":"Yerba Mate (\n                     Ilex paraguariensis\n                   A. St.\u2010Hil.) Reduces Oxidative Stress and Bone Resorption in Apical Periodontitis","volume":"59","author":"Wajima C. S.","year":"2025","journal-title":"International Endodontic Journal"},{"issue":"15","key":"e_1_2_10_32_1","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.3390\/ma12152476","article-title":"Cross\u2010Linking Strategies for Electrospun Gelatin Scaffolds","volume":"12","author":"Campiglio C. E.","year":"2019","journal-title":"Materials (Basel)"},{"key":"e_1_2_10_33_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.bioactmat.2022.04.013","article-title":"Tissue\u2010Specific Melt Electrowritten Polymeric Scaffolds for Coordinated Regeneration of Soft and Hard Periodontal Tissues","volume":"19","author":"Daghrery A.","year":"2023","journal-title":"Bioactive Materials"},{"issue":"1","key":"e_1_2_10_34_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41368-024-00316-w","article-title":"Synthetic High\u2010Density Lipoprotein (sHDL): A Bioinspired Nanotherapeutics for Managing Periapical Bone Inflammation","volume":"16","author":"Dal\u2010Fabbro R.","year":"2024","journal-title":"International Journal of Oral Science"},{"issue":"7","key":"e_1_2_10_35_1","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/iej.14243","article-title":"Quercetin\u2010Calcium Hydroxide Scaffolds Modulate Dental Pulp Stem Cell Response In\u00a0Vitro Under a Simulated Inflammatory Environment","volume":"58","author":"Anselmi C.","year":"2025","journal-title":"International Endodontic Journal"},{"issue":"1","key":"e_1_2_10_36_1","doi-asserted-by":"crossref","first-page":"7173","DOI":"10.1038\/s41598-020-64041-0","article-title":"Immunoinflammatory Response and Bioactive Potential of GuttaFlow Bioseal and MTA Fillapex in the Rat Subcutaneous Tissue","volume":"10","author":"Delfino M. M.","year":"2020","journal-title":"Scientific Reports"},{"issue":"22","key":"e_1_2_10_37_1","doi-asserted-by":"crossref","first-page":"13761","DOI":"10.3390\/ijms232213761","article-title":"Electrospun Azithromycin\u2010Laden Gelatin Methacryloyl Fibers for Endodontic Infection Control","volume":"23","author":"Ayoub A. A.","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_10_38_1","doi-asserted-by":"crossref","first-page":"213427","DOI":"10.1016\/j.bioadv.2023.213427","article-title":"Multifunctional and Biodegradable Methacrylated Gelatin\/\n                     Aloe vera\n                   Nanofibers for Endodontic Disinfection and Immunomodulation","volume":"150","author":"Namazi S. S.","year":"2023","journal-title":"Biomaterials Advances"},{"issue":"18","key":"e_1_2_10_39_1","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.3390\/polym14183719","article-title":"Electrospinning of Biomedical Nanofibers\/Nanomembranes: Effects of Process Parameters","volume":"14","author":"Chinnappan B. 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J.","year":"2007","journal-title":"Acta Biomaterialia"},{"issue":"1","key":"e_1_2_10_42_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/jbm.a.32535","article-title":"The Performance of Dental Pulp Stem Cells on Nanofibrous PCL\/Gelatin\/nHA Scaffolds","volume":"93","author":"Yang X.","year":"2010","journal-title":"Journal of Biomedical Materials Research. Part A"},{"issue":"6","key":"e_1_2_10_43_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1177\/0885328216673555","article-title":"Understanding Drug Release From PCL\/Gelatin Electrospun Blends","volume":"31","author":"Munj H. R.","year":"2017","journal-title":"Journal of Biomaterials Applications"},{"issue":"1","key":"e_1_2_10_44_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40496-025-00421-7","article-title":"Advances in 3D Printed Scaffolds for Periodontal Regeneration","volume":"13","author":"Daghrery A.","year":"2026","journal-title":"Current Oral Health Reports"},{"key":"e_1_2_10_45_1","first-page":"5163603","article-title":"Tensile Properties of Three Selected Collagen Membranes","volume":"2019","author":"Raz P.","year":"2019","journal-title":"BioMed Research International"},{"issue":"3","key":"e_1_2_10_46_1","first-page":"209","article-title":"Rank\/Rankl\/opg: Literature Review","volume":"36","author":"Silva I.","year":"2011","journal-title":"Acta Reumatol\u00f3gica Portuguesa"},{"issue":"3","key":"e_1_2_10_47_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s00223-016-0215-6","article-title":"Theobromine Upregulates Osteogenesis by Human Mesenchymal Stem Cells In\u00a0Vitro and Accelerates Bone Development in Rats","volume":"100","author":"Clough B. 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