{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:30:32Z","timestamp":1792089032335,"version":"4.4.0"},"reference-count":25,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Poznan University of Medical Sciences, Poland"},{"name":"Eaglegrid Srl."},{"name":"University of Pisa, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Introduction: Titanium alloys currently are the most used material for the manufacture of dental endosseous implants. However, in partially or totally edentulous patients, varying degrees of maxillary bone resorption usually occur, making the application of these devices difficult or even impossible. In these cases, a suitable alternative is offered by subperiosteal implants, whose use is undergoing a revival of interest following the introduction of novel, computer-assisted manufacturing techniques. Several procedures have been developed for the modification of titanium surfaces so to improve their biocompatibility and integration with bone. Information is, however, still incomplete as far as the most convenient surface modifications to apply with subperiosteal implants, in which an integration with soft mucosal tissues is just as important. Objectives: The present study aimed at evaluating whether different treatments of titanium surfaces can produce different effects on the viability, attachment, and differentiation of gingival fibroblasts, i.e., the cell type mainly involved in osteointegration as well as the healing of soft tissues injured by surgical procedures, in order to verify whether any of the treatments are preferable under these respects. Methodology: The human immortalized gingival fibroblast (CRL-4061 line) were cultured in the presence of titanium specimens previously treated with five different procedures for surface modification: (i) raw machined (Ti-1); (ii) electropolished (Ti-2); (iii) sand-blasted acid-etched (Ti-3); (iv) Al Ti Color\u2122 proprietary procedure (Ti-4); and (v) anodized (Ti-5). At different times of incubation, viability and proliferation of cells, was determined along with the changes in the expression patterns of ECM-related genes involved in fibroblast attachment and differentiation: vinculin, fibronectin, collagen type I-alpha 1 chain, focal adhesion kinase, integrin \u03b2-1, and N-cadherin. Three different experiments were carried out for each experimental point. The release from fibroblasts of endothelin-1 was also analyzed as a marker of inflammatory response. The proliferation and migration of fibroblasts were evaluated by scratch tests. Results: None of the five types of titanium surface tested significantly affected the fibroblasts\u2019 viability and proliferation. The release of endothelin-1 was also not significantly affected by any of the specimens. On the other hand, all titanium specimens significantly stimulated the expression of ECM-related genes at varying degrees. The proliferation and migration abilities of fibroblasts were also significantly stimulated by all types of titanium surface, with a higher-to-lower efficiency in the order: Ti-3 &gt; Ti-4 &gt; Ti-5 &gt; Ti-2 &gt; Ti-1, thus identifying sandblasting acid-etching as the most convenient treatment. Conclusions: Our observations suggest that the titanium alloys used for manufacturing subperiosteal dental implants do not produce cytotoxic or proinflammatory effects on gingival fibroblasts, and that sandblasting acid-etching may be the surface treatment of choice as to stimulate the differentiation of gingival fibroblasts in the direction of attachment and migration, i.e., the features allegedly associated with a more efficient implant osteointegration, wound healing, and connective tissue seal formation.<\/jats:p>","DOI":"10.3390\/jfb14020059","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T02:52:21Z","timestamp":1674183141000},"page":"59","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Biocompatibility of Subperiosteal Dental Implants: Effects of Differently Treated Titanium Surfaces on the Expression of ECM-Related Genes in Gingival Fibroblasts"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1842-0551","authenticated-orcid":false,"given":"Marco","family":"Roy","sequence":"first","affiliation":[{"name":"Department of Prosthodontics and Gerostomatology, Poznan University of Medical Sciences, 60-792 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Corti","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa Medical School, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Dominici","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa Medical School, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6435-9325","authenticated-orcid":false,"given":"Alfonso","family":"Pompella","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa Medical School, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Cerea","sequence":"additional","affiliation":[{"name":"Independent Researcher, 24121 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Chelucci","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3659-7761","authenticated-orcid":false,"given":"Barbara","family":"Dorocka-Bobkowska","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics and Gerostomatology, Poznan University of Medical Sciences, 60-792 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-3087","authenticated-orcid":false,"given":"Simona","family":"Daniele","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3390\/prosthesis2020011","article-title":"Titanium Alloys for Dental Implants: A Review","volume":"2","author":"Nicholson","year":"2020","journal-title":"Prosthesis"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jamari, J., Ammarullah, M.I., Santoso, G., Sugiharto, S., Supriyono, T., Prakoso, A.T., Basri, H., and van der Heide, E. (2022). Computational Contact Pressure Prediction of CoCrMo, SS 316L and Ti6Al4V Femoral Head against UHMWPE Acetabular Cup under Gait Cycle. J. Funct. Biomater., 13.","DOI":"10.3390\/jfb13020064"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15390","DOI":"10.1038\/s41598-021-94980-1","article-title":"Improvement of an additively manufactured subperiosteal implant structure design by finite elements based topological optimization","volume":"11","author":"Carnicero","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1186\/s12935-022-02801-w","article-title":"Current methods for studying metastatic potential of tumor cells","volume":"22","author":"Bouchalova","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Marconi, G.D., Fonticoli, L., Della Rocca, Y., Oliva, S., Rajan, T.S., Trubiani, O., Murmura, G., Diomede, F., and Pizzicannella, J. (2021). Enhanced Extracellular Matrix Deposition on Titanium Implant Surfaces: Cellular and Molecular Evidences. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111710"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Marconi, G.D., Fonticoli, L., Della Rocca, Y., Rajan, T.S., Piattelli, A., Trubiani, O., Pizzicannella, J., and Diomede, F. (2021). Human Periodontal Ligament Stem Cells Response to Titanium Implant Surface: Extracellular Matrix Deposition. Biology, 10.","DOI":"10.3390\/biology10090931"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.4028\/www.scientific.net\/AMM.66-68.2202","article-title":"Laser metal deposition shaping system for direct fabrication of parts","volume":"66\u201368","author":"Zhang","year":"2011","journal-title":"Appl. Mech. Mater."},{"key":"ref_8","unstructured":"Pou, J., Riveiro, A., and Davim, J.P. (2021). Handbooks in Advanced Manufacturing, Additive Manufacturing, Elsevier."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jobcr.2019.04.004","article-title":"Current status and applications of additive manufacturing in dentistry: A literature-based review","volume":"9","author":"Javaid","year":"2019","journal-title":"J. Oral Biol. Craniofac. Res."},{"key":"ref_10","first-page":"35","article-title":"The subperiosteal implant as a viable long-term treatment modality in the severely atrophied mandible: A patient\u2019s 40-year case history","volume":"21","author":"Kurtzman","year":"1995","journal-title":"J. Oral Implantol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5420391","DOI":"10.1155\/2018\/5420391","article-title":"Custom-Made Direct Metal Laser Sintering Titanium Subperiosteal Implants: A Retrospective Clinical Study on 70 Patients","volume":"2018","author":"Cerea","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Roy, M., Corti, A., Dorocka-Bobkowska, B., and Pompella, A. (2022). Positive Effects of UV-Photofunctionalization of Titanium Oxide Surfaces on the Survival and Differentiation of Osteogenic Precursor Cells\u2014An In Vitro Study. J. Funct. Biomater., 13.","DOI":"10.3390\/jfb13040265"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"603072","DOI":"10.3389\/fbioe.2020.603072","article-title":"Surface Modification Techniques of Titanium and its Alloys to Functionally Optimize Their Biomedical Properties: Thematic Review","volume":"8","author":"Xue","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/jopr.13226","article-title":"Are Denture Adhesives Safe for Oral Cells?","volume":"30","year":"2021","journal-title":"J. Prosthodont."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E264","DOI":"10.2341\/20-245-L","article-title":"In Vitro Biocompatibility of CPP-ACP and Fluoride-containing Desensitizers on Human Gingival Cells","volume":"46","year":"2021","journal-title":"Oper. Dent."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/j.1600-0501.2006.01277.x","article-title":"Focal adhesion contact formation by fibroblasts cultured on surface-modified dental implants: An in vitro study","volume":"17","author":"Herzog","year":"2006","journal-title":"Clin. Oral Impl. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1089\/scd.2009.0048","article-title":"Differentiation of dermal multipotent cells into odontogenic lineage induced by embryonic and neonatal tooth germ cell-conditioned medium","volume":"19","author":"Huo","year":"2010","journal-title":"Stem Cells Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/B978-0-12-386043-9.00005-0","article-title":"New insights into vinculin function and regulation","volume":"287","author":"Peng","year":"2011","journal-title":"Int. Rev. Cell. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.cellsig.2017.04.010","article-title":"Endothelin-1 promotes hypertrophic remodelling of cardiac myocytes by activating sustained signalling and transcription downstream of endothelin type A receptors","volume":"36","author":"Archer","year":"2017","journal-title":"Cell Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1034\/j.1600-0765.2003.00668.x","article-title":"Expression of endothelin-1 in gingival epithelial cells","volume":"38","author":"Yamamoto","year":"2003","journal-title":"J. Periodontal Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2220\/biomedres.30.349","article-title":"Relationship between endothelin-1 and interleukin-1beta in inflamed periodontal tissues","volume":"30","author":"Rikimaru","year":"2009","journal-title":"Biomed. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1038\/s41598-020-58585-4","article-title":"Analysis of Endothelin-1 Concentrations in Individuals with Periodontitis","volume":"10","author":"Isola","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1002\/jbm.a.36651","article-title":"Epithelial sealing effectiveness against titanium or zirconia implants surface","volume":"107","author":"Atsuta","year":"2019","journal-title":"J. Biomed. Mater. Res.-A"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"791725","DOI":"10.1155\/2015\/791725","article-title":"Surface Modifications and Their Effects on Titanium Dental Implants","volume":"2015","author":"Jemat","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10856-015-5481-8","article-title":"Assessment of human gingival fibroblast interaction with dental implant abutment materials","volume":"26","author":"Rutkunas","year":"2015","journal-title":"J. Mater. Sci.-Mater. Med."}],"container-title":["Journal of Functional Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4983\/14\/2\/59\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:11:20Z","timestamp":1760119880000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4983\/14\/2\/59"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,20]]},"references-count":25,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jfb14020059"],"URL":"https:\/\/doi.org\/10.3390\/jfb14020059","relation":{},"ISSN":["2079-4983"],"issn-type":[{"value":"2079-4983","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,20]]}}}